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Panayiotopoulos CP. The Epilepsies: Seizures, Syndromes and Management. Oxfordshire (UK): Bladon Medical Publishing; 2005.

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The Epilepsies: Seizures, Syndromes and Management.

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Chapter 12Symptomatic and Probably Symptomatic Focal Epilepsies

Topographical Symptomatology and Classification
Clinical note

Focal (anatomical, topographical or localisation related) epilepsies* are defined as seizures that emanate from an epileptogenic focus anywhere within the brain.1 Ictal symptoms, particularly at onset, are determined by localisation and not by aetiology. However, it is difficult to assign some epilepsies to specific anatomical localisations or lobes, as is often the case with seizures originating from clinically silent epileptogenic regions.

The ILAE Commission (1989) classifies focal epilepsies according to their topographical/anatomical origin as:1

  • Temporal lobe epilepsies
  • Frontal lobe epilepsies
  • Parietal lobe epilepsies
  • Occipital lobe epilepsies

These epilepsies may be idiopathic, cryptogenic or symptomatic. The new diagnostic scheme considers ‘symptomatic (or probably symptomatic) focal epilepsies’ as a separate group from ‘idiopathic focal epilepsies’.2 This is because of the significant progress made in recent years through the investigation of neurosurgical cases, technological advances in brain imaging methodologies and genetics. This distinction is important in practice, because the prognosis and treatment of idiopathic focal epilepsies differ significantly from those of symptomatic epilepsies. There is now concrete evidence to accept, diagnose and treat certain focal epilepsies on the basis of aetiology rather than simply localisation. Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, which is one of the commoner and most distinct epileptic syndromes, is a striking example of this.

The new ILAE diagnostic scheme further classifies focal epilepsies according to whether they are limbic or neocortical:2

Limbic Epilepsies

Mesial temporal lobe epilepsy with hippocampal sclerosis

Mesial temporal lobe epilepsy defined by specific aetiologies

Other types defined by location and aetiology

Neocortical Epilepsies (See Pages 207–221)

Rasmussen syndrome (page 207)

Hemiconvulsion-hemiplegia syndrome (page 215)

Lateral temporal lobe epilepsy

Migrating focal seizures of early childhood (page 217)

Other types defined by location and aetiology

Simple and complex focal seizures may account for 60–70 % of all epilepsies and nearly half originate from temporal lobe structures.3–5 There are numerous causes of focal symptomatic and probably symptomatic focal epilepsies, such as benign or malignant tumours, viral and other infectious and parasitic diseases, cerebrovascular disorders, malformations of cortical development, genetically determined brain and metabolic disorders, trauma and other injuries. The exact prevalence of these aetiological factors in various types of focal epilepsies has not been estimated precisely, and certainly varies significantly between developed and developing countries. For example, cysticercosis and tuberculomas are among the commonest causes of epilepsies in developing countries, but have a minimal prevalence in Western industrialised countries. Malformations of cortical development, which are a significant cause of focal epilepsies, are often revealed only by high resolution MRI.6

The other idiopathic and hereditary forms of focal epilepsies have been detailed mainly in Chapters 10 and 11.

Temporal Lobe Epilepsies

Temporal lobe epilepsies comprise a heterogeneous group of disorders sharing the same topographical seizure onset (the temporal lobe), but often of diverse aetiology, age at onset, prognosis, and response to medical or surgical management. Anatomically they are broadly divided into those originating from the lateral or mesial regions of the temporal lobe (Figures 12.1 and 12.2). Mesial (or medial) is far more common (accounting for two-thirds of cases) than lateral temporal lobe epilepsy (LTLE). The most common of all is hippocampal epilepsy, which probably constitutes a disease with known pathology rather than a syndrome. Other causes of temporal lobe epilepsy, mesial or lateral, are benign or malignant tumours, viral and other infectious and parasitic diseases, cerebrovascular disorders, malformations of cortical development, trauma and other injuries.7 The other idiopathic and hereditary forms of temporal lobe epilepsy have been detailed in Chapters 10 and 11. Onset, progress and response to treatment largely depend on causative factors. Ictal manifestations distinguishing lateral from MTLE are often, but not always, pathognomonic. Seizures from other anatomical brain locations may present with similar semiology, mainly because of spread to temporal lobe structures.

Figure 12.1. MRIs of two patients with mesial (right) and lateral (left) temporal lobe epilepsy due to dysembryoplastic neuroepithelial tumours (DNET).

Figure 12.1

MRIs of two patients with mesial (right) and lateral (left) temporal lobe epilepsy due to dysembryoplastic neuroepithelial tumours (DNET). Left: Coronal FLAIR MRI showing a discrete ring-like lesion in the lateral aspects of the (more...)

Figure 12.2. Ictal EEG of 2 patients with hippocampal epilepsy.

Figure 12.2

Ictal EEG of 2 patients with hippocampal epilepsy. Top and middle: This was the first EEG of a boy aged 6 referred for episodes of panic attacks and a recent GTCS. The resting EEG was entirely normal but one of his (more...)

Classification and Definition

According to the ILAE Commission (1989)1

“Temporal lobe syndromes are characterized by simple focal seizures, complex focal seizures, and secondarily generalized seizures, or combinations of these. Frequently, there is a history of febrile seizures, and a family history of seizures is common. Memory deficits may occur. On metabolic imaging studies, hypometabolism is frequently observed [e.g., positron emission tomography]. Unilateral or bilateral temporal lobe spikes are common on EEG. Onset is frequently in childhood or young adulthood. Seizures occur in clusters at intervals or randomly.

General characteristics

Features strongly suggestive of the diagnosis when present include:

1.Simple focal seizures typically characterized by autonomic and/or psychic symptoms and certain sensory phenomena such as olfactory and auditory (including illusions). Most common is an epigastric, often rising, sensation.

2.Complex focal seizures often but not always begin with motor arrest typically followed by oroalimentary automatisms. Other automatisms frequently follow. The duration is typically >1 min. Postictal confusion usually occurs. The attacks are followed by amnesia. Recovery is gradual.

Electroencephalographic characteristics

In temporal lobe epilepsies the interictal scalp EEG may show the following:

1.No abnormality.

2.Slight or marked asymmetry of the background activity.

3.Temporal spikes, sharp waves and/or slow waves, unilateral or bilateral, synchronous but also asynchronous. These findings are not always confined to the temporal region.

4.In addition to scalp EEG findings, intracranial recordings may allow better definition of the intracranial distribution of the interictal abnormalities.

In temporal lobe epilepsies various EEG patterns may accompany the initial clinical ictal symptomatology, including (a) a unilateral or bilateral interruption of background activity; and (b) temporal or multilobar low-amplitude fast activity, rhythmic spikes, or rhythmic slow waves. The onset of the EEG may not correlate with the clinical onset depending on methodology. Intracranial recordings may provide additional information regarding the chronological and spatial evolution of the discharges.” 1

Demographic Data

Temporal lobe epilepsy may comprise 30–35% of all epilepsies. Two-thirds of these epilepsies originate from the mesial and the other third from the lateral temporal lobe regions. The commonest cause, in neurosurgical series, is hippocampal sclerosis, which accounts for 65% of cases.8–11 Men and women are equally affected. Age at onset largely depends on aetiology.

Classification

The ILAE Task Force classifies temporal lobe epilepsies as:2

Limbic Epilepsy

  • Mesial temporal lobe epilepsy with hippocampal sclerosis
  • Mesial temporal lobe epilepsy defined by specific aetiologies

Neocortical Epilepsy

  • Lateral temporal lobe epilepsy

Clinical Manifestations of Temporal Lobe Seizures

Temporal lobe epilepsy manifests with:

  • Simple focal seizures
  • Complex focal seizures
  • Secondarily generalised tonic clonic seizures (GTCS)
  • Focal non-convulsive status epilepticus (limbic or neocortical)
  • Secondarily convulsive status epilepticus

Ictal clinical symptoms of temporal lobe epilepsy can be subjective, objective or both. They have been accurately localised and studied in neurosurgical series of patients. Simple focal seizures manifest with subjective symptoms of illusions, hallucinations or both (also called auras). These last from a few seconds to 1–2 min. They may be the only seizure type, but commonly progress to complex focal seizures during which objective symptoms, such as automatisms and motor manifestations, appear. Autonomic disturbances are common at any stage of the ictus. Secondarily GTCS may be frequent or rare and one-tenth of patients may never experience GTCS. Postictal fatigue and drowsiness are common.

The clinical manifestations of temporal lobe epilepsy are well described in relevant textbooks. Excellent descriptions can be found in old12–27 and relatively newer reports28–34 and reviews35–39 devoted to this vast subject.

Subjective Ictal Clinical Manifestations

Subjective ictal clinical manifestations constitute a galaxy of various simple or complex sensations of illusions, hallucinations or both. They are also called auras because they are the first subjective symptom of an epileptic seizure prior to the impairment of consciousness. These symptoms are experienced by nearly all patients (> 90%) with temporal lobe epilepsy.28,31,35,37,39–41 They can be the only ictal symptom of a focal seizure, but frequently progress to other manifestations of complex focal seizures.42,43

Epigastric aura and fear are the commonest and often the initial manifestations of mesial temporal lobe seizures. Simple or complex auditory hallucinations mainly characterise LTLE. Mental hallucinations and illusions are common in both. Olfactory and gustatory hallucinations are less common.

Subjective ictal symptoms of temporal lobe seizures, in order of prevalence, include:

  • ascending epigastric aura
  • experiential (mental or psychic) symptoms
  • fear and panic
  • déjà vu or jamais vu and their variations
  • auditory hallucinations and illusions
  • olfactory and gustatory hallucinations
  • other symptoms.
Epigastric or Visceral Aura
Clinical note

Epigastric or visceral aura is by far the commonest symptom of mesial temporal lobe seizures.40,44,45 It is defined by location, quality, duration, movement and associated symptoms in progression.

Location

It is usually felt in the upper half of the abdomen44 with most patients pointing with the palm of one or both hands to a wide area between the end of the sternum and the umbilicus. Of hundreds of patients I have interrogated, I do not recall anyone pointing with a finger instead of the palm or lateralising to one side or the other. Less than 10% of 100 patients thoroughly studied by Van Buren (1963) pointed slightly lateral to the midline.44

Quality

Epigastric aura is often initially described as pain, but on further questioning is rarely pain. It is a strange ‘difficult-to-describe’ sensation in that area for which the most common description I get is as ‘if the organs inside are squeezed and twisted’. Other descriptions are of emptiness, rolling, turning, whirling, tenderness, fluttering, butterflies, pressure, burning, nausea, emptiness and their variations.44 Genuine pain, sometimes excruciating, is exceptional, but does occur.

Duration

This is usually short, a few seconds, but becomes longer with the appearance of other symptoms as the seizure progresses. I am not aware of any report of ‘epigastric status epilepticus’, but it may occur:

Patient note

A patient with typical MRI and PET scan evidence of right-sided hippocampal sclerosis had frequent seizures starting with an ascending abdominal sensation of discomfort in the stomach “as though being in a lift that stops abruptly”. This often progressed to a feeling of disorientation and “shivering”, and sometimes déjà vu prior to losing consciousness witnessed as: “stares and fiddles or drums with his fingers on a table”. He also had clusters of the same “intense abdominal discomfort and a feeling of shivering” lasting for 2–5 minutes, becoming repetitive at intervals of 1 hour for approximately half a day to 2 days. Within that period lengthy attacks of more than half an hour occurred.

Movement

An ascending epigastric sensation is probably the most characteristic feature of this type of epileptic seizure. Irrespective of quality, this sensation often moves upwards in a slow or fast fashion (within seconds) and, interestingly, it is when it reaches the level of the throat that the patient loses consciousness. Downward movement towards the feet is exceptional.

Fear

Fear is the commonest aura after epigastric sensations in mesial temporal lobe seizures. It is an affective mental symptom. There are two aspects to this. Firstly, fear may be a symptom of a seizure itself. Secondly, fear may be the realistic and natural reaction to an impending convulsion heralded by an aura. In some cases, the one cannot be disentangled from the other, although in most patients fear is an evidenced ictal event.

The intensity and quality of ictal fear varies considerably between patients, though it is stereotypical in each individual. Most patients use the terms ‘fear’ and ‘panic’ synonymously. It is not directed towards any particular circumstance, event or person. It is just fear or panic that may be the first, and sometimes the only, ictal symptom.

Patient note

“I am scared, I have my panic” a 5-year-old boy said during a 2-min video-EEG recorded seizure without other subjective or objective symptoms (Figure 12.2).

More often, fear appears with other symptoms at the beginning or during the course of the seizure.

Patient note

It starts with my panic and that stomach feeling, and then I pass out.

Fear is not specific to only mesial temporal lobe seizures. Although it is mainly associated with amygdaloid, periamygdaloid and hippocampal stimulation, neocortical areas can also be responsible. A typical example is the fear of frontal lobe seizures. However, there is a major difference between the fear of temporal versus frontal lobe epilepsy:

Patient note

Fear in mesial temporal lobe seizures is predominantly subjective “I am scared, I am in a terrible panic”, which is not apparent to the observer. Conversely, in frontal seizures, ‘fear’ is predominantly expressive, such as ‘his face is fearful’.

I have reached this conclusion after comparing relevant video EEG recordings of a significant number of patients. In temporal lobe seizures, patients feel intense fear or panic while, at the same time, they look relatively calm or their ‘fearful’ expression is disproportional to the intensity of their panic. Conversely, patients with frontal lobe seizures look so very terrified, which is disproportional to the actual subjective experience of fear. This differentiation should be expected: the temporal lobe is dealing with emotions/memory, while the frontal lobe dictates expression/movement.

Important note

Briefly, ‘fear’ is mainly felt emotionally in mesial temporal lobe seizures and mainly expressed facially in frontal seizures.

Experiential Symptoms (Mental, Intellectual or Psychic Symptoms, Dreamy States)

Experiential symptoms (also described as mental, intellectual or psychic symptoms, or dreamy states) of temporal lobe seizures are hallucinations, illusions or both. They may involve any faculty of the human mind: thinking, emotion, memory and recollection, chronological order, speed, sensation, reality and unreality, and their interactions with past, present and imaginary experiences. Events and experiences may be reproduced intact or disturbed: the present may be misplaced to the past, and the past to the present; real may be seen as unreal and vice versa; time may be speeded up or slowed down; and shape and other morphology may be natural or unnatural, and deformed or undistorted. Mental ictal symptoms may be very simple and natural, such as the ‘déjà vu’ phenomenon, a sensation of ‘fear and panic’ or a mild sense of depersonalisation such as “who am I?”, that may also be experienced by normal people who do not have seizures. On other occasions, these symptoms may be more complicated with a complete distortion of time, space, morphology, direction, experience and normality.

The mental ictal manifestations of temporal lobe seizures typically combine elements of perception, memory and affect that, as in real life, are often encompassed together in a unified subjective symptom.28 Perceptual, mnemonic or affective aberrations usually cluster in various combinations and various degrees of disturbance. However, one aberration may be more involved than another; sometimes, one may be exclusively affected and may occur in isolation. Depending on the predominant mental aberration, they are subdivided under various names, such as: ideational (impairment of thoughts), dysmnesic (impairment of memory), affective (emotional impairment)46 and dyscognitive (impairment of perception, cognition).

Déjà Vu

Déjà vu is another common symptom that is experienced exclusively as an ictal phenomenon in temporal lobe seizures. Déjà vu is a natural event that has been experienced by most normal people and the term is used in everyday life. In temporal lobe epilepsy, déjà vu is signified by the presence and the sequence of other epileptic events that may precede, coincide or follow it.

Nomenclature Issues

‘Dreamy states’, ‘psychic or mental symptoms’, ‘intellectual aura’ and ‘experiential phenomena’ are the terms most widely used to denote symptoms of temporal lobe seizures that uniquely relate to the patient’s personality regarding identity, experience, emotion, thought and memory. These terms are not necessarily synonymous, because they are used in the relevant literature to encompass either limited or much wider ictal manifestations.

Hughlings Jackson14;15;47;48 introduced the term ‘dreamy state’ in favour of ‘intellectual aura’ or ‘psychical state’. He also used the word ‘psychical’ not as synonymous to the ‘dreamy state’, but to differentiate it from physical symptoms.

‘Peculiar mental state’ are the words used by Holmes.16

Of these terms, ‘psychic symptoms’1 became popular first and ‘dreamy state’ second. Other terms used are ‘mental aura’ or ‘mental symptoms’ that may be illusionary or hallucinatory. ‘Psychic’ has inappropriate connotations and implications. Furthermore, these symptoms are transient mental, not psychic, aberrations. Patients have a clear insight that these are pathological symptoms for which they themselves seek medical advice. ‘Experiential phenomena’, introduced by Penfield49 and masterly detailed by Gloor (1993)31 and Bancaud et al. (1994),33 may be an appropriate term for only those manifestations that are based on previously experienced events. It is of limited value for ictal mental symptoms that are not related to previous experiences or in certain common circumstances that defy such experiential links.

Definition

Déjà vu is defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. Different mental components, such as memory, attention and perception, are associated with this distinct experience.

‘Déjà vu’ (already seen) is commonly used in a much broader sense, to include ‘déjà entendu’ (already heard) and ‘déjà veçu’ (already lived, experienced), as a false feeling of having experienced, seen and heard something before that is actually happening now. In déjà vu, the physical recognition is correct, but it is inappropriately connected with mental, emotional, experiential and timing processes that are associated with other physical presentations. The feeling of familiarity supervenes. It is mainly, a feeling of immense and vivid familiarity with the present situation irrespective of whether the content is visual, auditory or of any other physical presentation. The patient may say “that it is as if I have seen, heard or lived this before”, but more often the expression is “it was so familiar to me”.33,50

Patient note

Extreme familiarity with people and surroundings, as if I knew them well, as if they were close friends or relatives, intimate relations, as if it was my everyday experience. It is more of a feeling of knowing them well than of visual or auditory recognition and experience.

Seizures start with a strong feeling of extreme familiarity with what he sees, hears or happens at the moment. The feeling is so intense and vivid that on one occasion when this happened while playing cards with his wife, he thought that he knew exactly the next sequence of cards to be played.

The precise origin of déjà vu is still controversial (see for review ref 50). On the basis of intracranial EEG monitoring and stimulation studies, three possible sites of dysfunction have been proposed: (a) the mesial temporal lobe especially in the non-dominant hemisphere; (b) the superior lateral temporal cortex; and (c) a neuronal network that engages both mesial and lateral aspects of the temporal lobe. However, it is uncertain whether the temporal lobe disturbance is sufficient and necessary for the generation of déjà vu, since it is difficult to evaluate wider cortical regions using intracranial recordings. Based on PET scan studies, Adachi et al. (1999)50 proposed that extensive cortical areas beyond the temporal lobe, such as the parietal and possibly other association areas, may be involved in the network that integrates the déjà vu experience. Involvement of the left hemisphere, irrespective of the side of ictal onset, seems to be of particular importance for the generation of the déjà vu experience.

Jamais Vu, Jamais Entendu and Jamais Veçu

Jamais vu (never seen), jamais entendu (never heard) and jamais veçu (never experienced before) are similar as the jamais vu expressions for illusions “during which the subject’s surroundings even when familiar are no longer recognised, although they are clearly perceived by the subject”. Jamais vu is commonly used in a much broader sense to include jamais entendu and jamais veçu. It is a false feeling of unfamiliarity (has not been experienced, seen or heard) with something that has been previously encountered.

Jamais vu is much rarer than déjà vu, but it is well described by some patients with temporal lobe epilepsy. Similar to ‘déjà vu/familiarity’, in ‘jamais vu/unfamiliarity’, the feeling of unfamiliarity is stronger than the visual, auditory or other sensorial component. Visual, auditory and any other physical recognition is correct, but the connections to the mental and emotional processes associated with them are missing.

Patient note

I know that she is my mother but I do not feel that she is. Her features do not change. She is still my mother but I do not have the same human attachment to her. She is a stranger with the looks, the voice and the manners of my mother. She is a stranger.

Auditory Hallucinations and Illusions

Auditory hallucinations are attributed to lateral temporal lobe seizures, which are much less common than mesial temporal lobe seizures. They may be elementary or complex auditory hallucinations.

Elementary auditory hallucinations are crude and described as buzzing, ringing, hissing, fizzing, whistling, humming, shrilling, sizzling or clicking auditory sensations. High pitch noises are more frequently reported. They mainly originate from the activation of Heschl’s auditory cortex in the superior temporal gyrus. For many patients, this ‘buzz’ is the aura and the start of the seizure itself.

Patient note

Here it is again. That buzzing in both ears. It is just buzz. I cannot describe it. A buzz. There is nothing else. No voice, no identifiable noise that simulates anything else, just a buzz.

Complex auditory hallucinations consist of voices, music or other sounds that may be familiar or unfamiliar, friendly or aggressive and offensive, clear or indefinable, meaningful or incomprehensible. Complex auditory hallucinations are rarely the first ictal symptom and they usually combine with other visual or mental ictal symptoms of the ‘dreamy state’. These are mainly elicited by activation of the associated auditory cortex. Auditory hallucinations of hearing a voice are almost always without semantic content, even though the voice may sound familiar and may be identifiable.31 The affective tone of the voice is, however, often recognised.

Patient note

“It is a clear voice of a woman, she says something that I do not remember”, “conversations of people talking next door”, “a hoarse voice of a man saying that I have to go”, “sounds of human voices and animals”, “I hear the same voice saying the same thing. I know it at the time but I can not recall it afterwards”, “a voice filtered as if spoken through a handkerchief”, “it is my own voice talking to myself”, “voices through an amplifier or a loud speaker.”

Hearing music, often the same piece for every seizure, is uncommon though it is frequently cited in the literature and can be reproduced during electrical stimulation studies. 18,51–53 A song, usually a nursery rhyme, may be more common than music.

Auditory illusions are altered perceptions and interpretations of sounds, voices and conversations in the actual environment during the seizure. This may refer to simple changes of intensity, resonance, spatial orientation, tone, echo and clarity or be more complicated. Sounds and voices may appear louder/deafening/earsplitting or dim/faded, nearer or further away, clearer or disturbed, higher or lower pitched, echoed and variations of all of these.

Patient note

“the voices fade away”, “my hearing is heightened so I can hear everything loud and high pitched”, “as if talking from a distance”, “the voices become hoarse”, “a woman’s voice sounds like a man’s voice or like that of an animal”, “the sounds become so intense as if somebody has put the radio at maximum volume next to your ears”, “I hear the echo of the voices”, “as if you are in an empty church, you hear the sounds and their echoes.”

Olfactory and Gustatory Hallucinations

Olfactory epileptic auras are rare, constituting about 0.9% of all auras, and are typically, but not necessarily, unpleasant.54–56 The amygdala is the most likely symptomatogenic zone of olfactory auras. Tumours54 and hippocampal sclerosis56 are common causes.

Patient note

“a strong smell of gas or something like this”, “a smell of rotten leaves”, “a smell of perfume”, “a peculiar odour that I can not describe”.

Gustatory epileptic auras are hallucinations of taste that are usually unpleasant (rotten food) or a strange taste. They are usually generated in the insula or superior Sylvian bank.55,57,58

Patient note

“a strange taste of food in my mouth”, “a taste of burnt food”, “a taste of rotten food”, “taste of funny food in my mouth.”

Visual Hallucinations and Illusions

Visual hallucinations and visual illusions are detailed in the discussion of occipital lobe epilepsies.

Elementary visual hallucinations originate in the visual cortex. They do not feature in temporal lobe seizures except after secondary spread to the occipital lobes.

Complex visual hallucinations originate from the occipito-parietal-temporal junction and therefore may be part of any seizure that starts from or spreads to this area.

Complex visual hallucinations may take the form of persons, animals, objects, figures or scenes. They may be static or moving, real or unreal, normal or distorted in size, shape and dimension. They often progress to more complex visual hallucinatory experiences. They may be familiar or unfamiliar, friendly, frightening or grotesque. They may or may not be related with a past visual experience or connected with past events. In two patients reported by Penfield and associates,59,60 habitual complex visual hallucinations could be elicited by stimulation of the right posterior temporal regions.

An influential report on this subject has been written by Lance (1976)61 and the topic has been effectively reviewed by Kolmel (1993).62

Gordon Holmes (1927),16 in differentiating visual hallucinations of occipital from temporal lobe epilepsy, clearly stated:

Patient note

“More complicated subjective visual phenomena associated with local lesions in the neighbourhood of the uncus of the temporal lobe are different in origin and nature to those of occipital epilepsy. These uncinate epileptic seizures frequently begin with subjective smells and tastes, which are almost invariably of an unpleasant, usually of an extremely disagreeable, character; often there is, too, an epigastric sensation which may account to actual nausea. Then comes that peculiar mental state which Jackson called the ‘dreamy state’ or ‘intellectual aura’ characterised by a feeling of unreality of the present or familiarity with the events of the moment as though they had been experienced before. Often visions, which the patient associates with the past come up. A patient whom I had under observation always saw, in this stage a woman with a red cloak approaching nearer and nearer until, as the spectre reached her, she lost consciousness. In other cases, the vision may be of a scene tinted with a tone of familiarity, a building or a similar object. In such cases the visual hallucinations, for to these the term hallucination can be applied, is only part of the intellectual aura of Jackson and is obviously the result of more complicated cerebral and psychological processes than the perception and projection of lights and colour.”

Usually, auditory and visual hallucinations occur together. These are complex hallucinations of a scene, people, animals, objects, voices, music or the noise of a train. The content of these hallucinations usually appears familiar, but it may be entirely strange or unidentifiable.

Ictal Urinary Urge

Ictal urinary urge indicates seizure onset in the non-dominant temporal lobe.63 Six patients with temporal lobe seizures characterised by an aura of ictal urinary urge were recently described.63 In ictal single photon emission computed tomography (SPECT) of two patients, there was hyperperfusion of the insular cortex, indicating a critical role of the insula in the generation of the urinary urge.

Objective Ictal Symptoms

Objective ictal symptoms of temporal lobe epilepsy usually occur when consciousness is impaired. The patient is seldom aware of them. They are described by witnesses or captured on video recordings.

Objective ictal symptoms in order of prevalence include:

  • Automatisms
  • Autonomic disturbances
  • Speech disturbances
  • Head and eye deviation as well as dystonic postures
  • Motor arrest with staring
  • Unilateral ictal paresis
  • Unilateral eyelid blinking
  • Ictal vomiting

In general, nearly all of these ictal symptoms are not specific to temporal lobe seizures. Recent reviews and reports of temporal lobe epilepsy have emphasised objective symptoms only because of their lateralising value.

Automatisms

Oro-alimentary automatisms, which are often followed by simple gestural automatisms, are characteristic of MTLE only if preceded by epigastric aura, fear and mental symptoms of the ‘dreamy state’ of Jackson, alone or in combination.34,37,39,64–67 Oro-alimentary automatisms are more likely to begin in the first part of a complex focal seizure after the aura. They are attributed to seizures originating from the amygdala and periamygdaloid region, and not from the hippocampus. However, hippocampal after-discharges invariably spread to the amygdala, which explains the high prevalence of these automatisms in MTLE.

Important note

Simple automatisms, devoid of behavioural changes, are of no diagnostic significance in temporal lobe epilepsy. They are among the commonest symptoms in childhood and juvenile absence epilepsy. They are differentiated by clustering of other symptoms, duration and EEG manifestations.

Verbal automatisms of coherent speech are associated with seizure onset in the non-dominant hemisphere.38,70 Ictal vocalisation probably has no lateralising value.70 Both ictal vocalisation and verbal automatisms can occur in extratemporal epilepsies, such as frontal lobe seizures; they often occur in childhood and juvenile absence epilepsy.71

Definitions of Automatisms

Automatisms are coordinated involuntary simple movements or more complex acts performed by a patient who is unaware of them, because consciousness is sufficiently impaired. The patient is totally amnesic of this behaviour.

Automatisms are defined by the ILAE as “A more or less coordinated, repetitive, motor activity usually occurring when cognition is impaired and for which the subject is usually amnesic afterwards. This often resembles a voluntary movement, and may consist of inappropriate continuation of ongoing preictal motor activity.”68

According to Jackson “They have one common character –they are automatic; they are done unconsciously, and the agent is irresponsible. Hence, I use the term mental automatism.”47;69 In the Dictionary of Epilepsy 46 automatisms are “more or less coordinated adapted (eupractic or dyspractic) involuntary motor activity occurring during the state of clouding of consciousness either in the course of, or after an epileptic seizure, and usually followed by amnesia for the event. The automatism may be simply a continuation of an activity that was going on when the seizure occurred, or, conversely, a new activity developed in association with the ictal impairment of consciousness. Usually, the activity is commonplace in nature, often provoked by the subject’s environment, or by his sensations during the seizure: exceptionally, fragmentary, primitive, infantile, or antisocial behaviour may occur.”

Automatisms may be simple or complex.

I. Simple automatisms, devoid of behavioural changes, manifest with simple involuntary movements and include: Oro-alimentary automatisms: lip smacking, lip pursing, chewing, licking, tooth grinding or swallowing

Vocal: single or repetitive utterances consisting of sounds such as grunts or shrieks

Verbal: single or repetitive utterances consisting of words, phrases or brief sentences, such as uttering, shouting, talking or singing words, sentences or phrases

Gestural: often unilateral: (a) fumbling or exploratory movements with the hand directed towards self or environment; fiddling, fumbling, picking, tapping, patting or plucking, rubbing or scratching the face and other gestural movements; and (b) movements resembling those intended to lend further emotional tone to speech

Ambulatory automatisms: well coordinated acts, such as walking straight or in circles, continuing cycling or even driving

Manual or pedal: bilateral or unilateral fumbling, tapping, manipulating movements

Mimetic: facial expression suggesting an emotional state, often fear68

II. Complex (behavioural)automatisms: rich in behavioural changes with complex acts performed without apparent awareness. Semi-purposeful or well-organised exploratory or inappropriate behavioural manifestations, such as embarrassing actions, undressing in public, chewing objects that are not edible, wandering or running inappropriately, or aggressive behavioural acts.

Automatisms may also be spontaneous or interactive

Spontaneous: stereotyped, involve only self, and are virtually independent of environmental influences Interactive: not stereotyped, involve more than self, and are environmentally influenced.

Complex automatisms rich in behavioural aberrations are also common in temporal lobe epilepsy, and also occur in extratemporal seizures; they are exceptional in typical absence seizures.

Spitting, either as an ictal or postictal event,72 and bicycling movements73 are also common in extratemporal seizures.

Automatisms involving masturbation or other sexually related behaviour are uncommon, though often mentioned even in brief textbook reviews; I have never encountered them. Ictal penile erection and ejaculation are autonomic disturbances.74,75

It is generally considered that unilateral automatisms are ipsilateral to the seizure onset.38 However, this has been debated by Elger (2000)76 and it is not applicable in patients with bilateral independent temporal spikes.77

Language and Speech Ictal Disturbances

In addition to vocal and verbal automatisms, speech arrest and language disturbances are frequent manifestations of temporal lobe seizures. The commonest of all is the inability to speak.

Patient note

“I know what is going on and I understand what they are saying, but I can not speak” is much more common than “I know what it is but I can not find the word”.

Ictal aphasia and ictal speech arrest have been attributed to seizure onset in the language-dominant temporal lobe.78 Clear ictal speech and quick recovery mainly characterise seizures of the non-dominant temporal lobe,38,65 while postictal aphasia and prolonged recovery are mainly features of seizures of the dominant temporal lobe.38

Motor Arrest, Staring and Temporal Lobe Absence

Motor and speech arrest together with staring and loss of consciousness may be the first objective symptom of a temporal lobe seizure. As a rule, they follow other subjective symptoms, but in around 10% of patients, they may occur alone from the beginning of the seizure. These symptoms are clinically similar to those of generalised absence seizures when examined in isolation. For this reason, this type of focal seizure is also called ‘temporal lobe absence’, a term that should be discouraged to avoid confusion with ‘generalised absence seizures’, which are completely different if other symptoms and duration are considered in their entirety.

The duration of motor arrest, staring and loss of consciousness varies, but usually lasts for 1 min. Occasionally, this may be the only manifestation of the seizure. The patient usually recovers without other concurrent symptoms, such as automatisms.

Motor Manifestations

Motor manifestations include eye and head deviation, as well as dystonic postures that occur in around one-fifth of patients. These symptoms, which are also detailed in other chapters, are not specific to temporal lobe seizures. Thus, eye and head deviation is a common symptom in frontal and occipital lobe seizures. Dystonic postures are more often related to the frontal than temporal lobe.

Motor manifestations, despite their insignificance for pure anatomical localisation, are of value with respect to possible lateralisation:

Early and casual deviation of the eyes and head, in the setting of other more typical mesial temporal lobe ictal symptoms, may be ipsilateral to the epileptogenic focus.38,79–81 Conversely, it is almost always contralateral if it occurs during the progression of the seizure, when it is also more violent and often followed by secondarily GTCS.37

Unilateral tonic or dystonic posturing of arm, leg and face was described by Ajmone-Marsan and Ralston19 who called it ‘larval M2e’ to differentiate it from that of frontal lobe seizures. It is often associated with ipsilateral automatisms. It is reliably contralateral to the epileptogenic focus.38

Unilateral eyelid blinking is ipsilateral to the epileptogenic focus.82

Unilateral ictal paresis is contralateral to the origin of the seizure.83

Autonomic Disturbances and Ictus Emeticus

Autonomic disturbances of any type are among the most frequent ictal symptoms of temporal lobe epilepsy.84–88

Cardiovascular symptoms, mainly tachycardia and arrhythmias, less often bradycardia, asystole or hypertension, are very common and may be a common cause of sudden death in temporal lobe epilepsies (Figure 12.3).75,84,88–93

Figure 12.3. Cardiac asystole soon after the onset of a right-sided temporal lobe seizure.

Figure 12.3

Cardiac asystole soon after the onset of a right-sided temporal lobe seizure. The patient is a 60-year-old man with seizures of MTLE of recent onset. Seizures start with a vague feeling of ascending epigastric sensation. He never had GTCS. (more...)

A brief respiratory arrest, a sigh or a gasp is common in the initial part of complex focal seizures. Hyperpnoea, hypopnoea or even apnoea may occur in the late seizure phase.75

Mydriasis, sometimes asymmetrical, is a frequent symptom associated with the arrest reaction.38,75 Miosis and hippus pupillae are also common.75

A feeling of ‘shivering cold’ is sometimes associated with piloerection.75 Salivation is common, but lacrimation and nasal secretion are rare.75

There are occasional reports of penile erection, and even ejaculation or other sexual ictal manifestations.74

Flushing or more often pallor are commonly encountered.75

Ictus emeticus (nausea, retching and vomiting), and particularly ictal vomiting, is exceptional in adult patients with temporal lobe seizures, but very common in children with Panayiotopoulos syndrome.

Important Clinical Note on Ictus Emeticus in Adults and Children

In adults, there are no more than 30 reported cases of ictal vomiting, which predominantly emanates from the non-dominant temporal lobe and usually occurs after seizure onset, concurrently with other symptoms, and the patient is amnesic of the events.77,94–97 Conversely, ictus emeticus in children is very common, usually occurs at the onset of the seizures and the patient has a good recollection of the event (see ictus emeticus in Panayiotopoulos syndrome page 235).98–100

Gelastic Seizures of Temporal Lobe Epilepsy

Ictal laughter is rare, but has been well documented in over 34 cases of temporal lobe epilepsy.101 It has been attributed mainly to right-76 and less often to left-sided102–104 extramesial seizures. Age at onset is variable with several cases starting in childhood. Gelastic seizures have been produced by stimulation of the temporobasal cortex in two candidates for surgery for non-gelastic seizures and explored with subdural electrodes.105

The clinical descriptions are variable; the laughter being natural or forced, unmotivated, associated or even reactional to a pleasant event or feeling.

The laughter commonly is devoid of any sensation and is accompanied by a break of contact. A few patients have described feelings of mirth associated with laughter105–108 or an immediate environment felt to be amusing or distorted.105,107 In one case, the seizures could be triggered by hyperextension of the back and, in another case, sexual sensation was reported prior to the development of laughter.108

In 50% of cases, other types of seizures occur concomitantly or precede the gelastic seizures.101

See also hypothalamic (gelastic) epilepsy.

Amnesic Seizures

In pure amnesic seizures, the only clinical manifestation is an inability to retain in memory what occurs during the seizure. Other cognitive functions are preserved and patients interact normally with their physical and social environment.109 Pure amnesic seizures of patients with temporal lobe epilepsy never represent the only type of seizure. This may suggest that they result from selective ictal inactivation of mesial temporal structures without neocortical involvement. Amnesic seizures occur most often in patients with neuropsychological and EEG evidence of bilateral dysfunction of mesial temporal lobe structures. More rarely, in unilateral dysfunction, amnesic seizures may be due to seizure discharge limited to the mesial temporal structures of both sides, probably as a result of contralateral spread from one to the other through the dorsal hippocampal commissure.109

Catamenial Temporal Lobe Seizures

Some women have exclusively catamenial seizures, which may demand different management.110,111

Patient note

A 32-year-old businesswoman had had strictly catamenial simple focal seizures since 13 years of age. On the third premenstrual day, she would have 10–14 seizures, 5–6 the next day, then 1–3 the next day and none until the next month when the same pattern of events was repeated. The seizures are stereotyped and last for around 30 s. Suddenly, she has a feeling of extreme familiarity with people and her surroundings. She also has the feeling that people or animals look alike. All her senses (smell, hearing, skin) are heightened. There is no apparent impairment of consciousness. Postictally, she is tired and has severe bifrontal postictal headache, which may last for hours. These progressed to loss of consciousness and mild convulsions on only three occasions. Treatment with valproate and later with carbamazepine did not have any effect. She did not take any medication after the age of 18 years. From around 20 years of age, the seizures improved dramatically and there was no catamenial relation after starting hormonal contraception.

Postictal Symptoms

Postictal symptoms are common, often characteristic and may be of value in lateralising temporal lobe seizures. Such symptoms include mental and physical fatigue, drowsiness, headache, language aberrations, inability to concentrate and confusion to varying degrees that is often severe and associated with automatic behaviour of which the patient may be amnesic. Some patients may wander about in the streets, behaving normally or in a socially unacceptable manner, having no recollection of the events when they recover.

In an attempt to reorient to the current situation, an embarrassing smile, coughing, spitting or sighing are early postictal symptoms (Figure 12.2).76,113

Postictal symptoms may be disproportionately more severe than the ictal manifestations and may last for hours.

Patient note

“Soon, perhaps a minute, afterwards, his actions, or I should say the irrelevant-seeming actions, ceased; he replied correctly to simple questions, and told me that it was not necessary for me to go home with him. He, however, looked confused and seemed strange. When we got to his house a few yards away, I thought he was fully recovered, and, as I was thinking of making another room on the ground floor of my house, I took the opportunity of speaking to him about a third room there was on the ground floor of his house. Among other things he said he used to breakfast there. I was surprised when he afterwards, next day, told me that he remembered nothing from the time of being in my room consulting me (before the fit) to a little time after I left him at his own house”. Jackson JH and Colman WS. 189815

Marked postictal manifestations may follow seemingly mild attacks and vice versa.

Patient note

I am so drained and exhausted with irresistible drowsiness.

I write the rest of my day off.

Significance of Postictal Symptoms in Lateralisation

Recent reports signified postictal aphasia and global disorientation as a lateralising symptom of the language dominant hemisphere.38,65,66 Conversely, well-formed ictal speech and rapid return to baseline postictally occur in non-dominant temporal lobe seizures.66 Contrary to these, Elger (2000)76 found postictal aphasia in both right and left hippocampal epilepsy, “possibly due to the spread of seizure discharges from right to left”.

Lateralised postictal motor deficits are contralateral to seizure origin.38,83

Differentiating Temporal Lobe Seizures from Other Extratemporal Seizures on the Basis of Postictal Symptoms

Postictal symptoms are far more common after temporal lobe than extratemporal seizure onsets. Postictal confusional states and automatisms are exceptional in extratemporal seizures. In frontal lobe seizures, the patient immediately recovers after the fit with no postictal manifestations. In visual occipital seizures, the only postictal abnormality is a severe migraine-like headache that often follows71.

A Brief Reminder of Catamenial Epilepsy

“Catamenial epilepsy is often vaguely defined as the occurrence of seizures around the time of menses or an increase in seizures in relation to the menstrual cycle.”111 Catamenial seizures increase in approximately one-third of women with focal or generalised epilepsies, but only a small proportion of these patients suffer from pure catamenial epilepsy (i.e. seizures occurring only in relation to their menses).

Catamenial epilepsy may be perimenstrual, periovulatory and luteal.111 The diagnosis is based on careful assessment of menstrual and seizure diaries, and characterisation of cycle type and duration.

Of a variety of mechanisms proposed, hormonal influences are the best established and exert significant effects on seizure threshold. Oestrogens have a proconvulsant effect, while progesterone has mainly anticonvulsant properties.111 However, in contrast to focal and secondarily GTCS, progesterone may exacerbate absence seizures and generalised spike and wave discharge (GSWD).111;112 The most common therapies proposed in small, uncontrolled or anecdotal reports include acetazolamide, cyclical use of benzodiazepines (mainly clobazam) or antiepileptic drugs (AEDs), and hormonal therapy. 111

Diagnostic Procedures

Brain MRI is the most important diagnostic test required for all patients with temporal lobe epilepsy to detect symptomatic causes.114–118 High resolution MRI may detect abnormalities in 90% of patients in neurosurgical series.

Magnetic resonance spectroscopy (MRS) offers valuable insights and is useful in the presurgical evaluation of patients. PET scanning and other functional brain imaging modalities are helpful for localisation.

The serum prolactin concentration may rise markedly 10 min after seizure onset in three-quarters of patients.119

Electroencephalography

Interictal EEG of MTLE is identical to that detailed in hippocampal epilepsy (see page 378), irrespective of aetiology.120–122 Briefly, in one-third of patients, the classical spike or sharp and slow wave is shown by the anterior temporal electrode (Figure 12.4), and the yield is increased with prolonged EEG recordings and sleep EEG.

Figure 12.4. EEG samples from two patients with hippocampal epilepsy.

Figure 12.4

EEG samples from two patients with hippocampal epilepsy. Left: Discrete runs of monomorphic theta activity are localised in the left anterior temporal regions in this patient with left hippocampal sclerosis. There were (more...)

In LTLE, spike and sharp wave complexes may be seen in the middle temporal electrode (Figure 12.5), but this is often indistinguishable from MTLE.

Figure 12.5. EEG of a woman aged 24 with LTLE.

Figure 12.5

EEG of a woman aged 24 with LTLE. Note the marked focal abnormalities of slow waves and sharp–slow wave complexes around the right anterior-midtemporal regions.

“Please, exclude temporal lobe epilepsy” is the commonest reason for requesting an EEG for any kind of transient behavioural aberration; it is often an impossible task.

About two-thirds of patients have a normal routine interictal EEG or show non-specific abnormalities with an excess of slow waves in one temporal lobe. Runs of monomorphic slow waves may be important for lateralisation and appear ipsilateral to seizure onset (Figure 12.4).123–125 Furthermore, in patients with temporal lobe epilepsy whose MRI is either normal or suggestive of hippocampal sclerosis, interictal temporal delta activity has a lateralising value similar to that of temporal spiking.125

Ictal EEG as detailed in hippocampal epilepsy is not significantly different in either MTLE or LTLE.126–128 It mainly consists of regional ipsilateral rhythmic 4–7-Hz activity (Figures 12.2 and 12.3). Less often, there is attenuation of the background rhythms and remission of the interictal spikes. In one study, the ictal EEG in LTLE revealed a lower mean frequency of lateralised rhythmic activity that frequently had a hemispheric distribution, whereas in MTLE seizures this was maximal over the ipsilateral temporal region.113

Differential Diagnosis

The typical temporal lobe seizures consisting of rising epigastric sensation, fear and progression to impairment of consciousness with oro-alimentary automatisms should be easy to diagnose.

Differentiation from Frontal Lobe and Other Extra-Temporal Seizures

Although various ictal symptoms of temporal lobe epilepsy may also occur with a varying degree of frequency in extratemporal lobe seizures, the vast majority of temporal lobe epilepsy offers no difficulty in differential diagnosis if symptoms are properly analysed, synthetically and chronologically.

A single ictal symptom may predominate in one or another type of seizure from various locations, but makes no significant contribution to diagnosis. For example, head deviation can occur in seizures from any location, which are identified by other concurrent symptoms, such as elementary visual hallucinations in occipital seizures, epigastric and other auras in temporal lobe epilepsy, and stereotypical and rather violent jerks of the head in frontal lobe seizures.

Another example is dystonic motor manifestations that are common in both temporal and frontal lobe epilepsy. However, in frontal lobe seizures, these manifestations are usually the very first symptom; they are brief and often occur without severe impairment of consciousness, mainly during sleep and with no postictal symptoms. There are no preceding symptoms of rising epigastric sensations, oro-alimentary automatisms, olfactory and gustatory hallucinations, or mental illusions and hallucinations.

The most frequent misdiagnosis is that of typical absence seizures in adults as temporal lobe seizures with which they have nothing else in common other than impairment of consciousness and automatisms.129

Prognosis

The prognosis is largely, but not exclusively, cause related. Thus, of the established syndromes, familial temporal lobe epilepsy is usually mild (page 353), while hippocampal epilepsy may take a progressive course that can be successfully halted by appropriate neurosurgical procedures. However, even in cases with the same cause, such as hippocampal epilepsy, the prognosis can vary significantly from mild to severe (page 389). In community studies, it appears that 10–40% or more of patients with epileptic seizures of temporal lobe origin may go into remission.130

Management

Management comprises AEDs and/or neurosurgical excision of the epileptogenic region.

A recent practice parameter for temporal lobe epilepsy and localised neocortical resections131,132 concludes:

“The benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable. For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered. Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes.”131,132

Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (Hippocampal Epilepsy)

MTLE with hippocampal sclerosis (MTLE-HS) or hippocampal epilepsy is the commonest and one of the most distinct epileptic diseases/syndromes with defined underlying hippocampal pathology shown on MRI, clinical seizure types and post-resection seizure relief.133,134 MTLE-HS has been the subject of a recent state-of-the art ILAE report.134 Experts discussed the definition, natural history, pathological features, pathogenesis, electroclinical, neurophysiological, neuropsychological, and structural and functional imaging findings of MTLE-HS.

The clinical features and prognosis of MTLE-HS derive almost exclusively from neurosurgical series of cases that are medically intractable.37,39,75,76,134–136 Therefore, they may not accurately represent the clinical spectrum of MTLE-HS, particularly with respect to severity and prognosis. The neurosurgical cases may represent the tip of the iceberg and the worst cases (about 20%). The vast majority of cases (80%) are not seen in these specialised neurosurgical centres, and some cases may be very mild and easily controlled with appropriate AEDs. I have seen an impressive number of professionals (physicians, nurses, solicitors, successful businessmen, teachers) and ordinary working class people that live a normal life, some with minor focal seizures, but others with an occasional secondary GTCS often controlled with AED monotherapy.

Patient note

A 35-year-old man had an excellent work and health record as a fire-fighter and driver for 11 years despite numerous seizures from 31 years of age.

The onset of seizures was inconspicuous with brief episodes (lasting a few seconds) of “an empty feeling in the stomach” with no other symptoms. However, 2 years later, these occurred on a daily basis and were associated with a “daydream, you disappear in your own world for a moment, a second”. He did not experience any overt loss of consciousness during these events, but he felt distant and he was told by his colleagues that he became aggressive. These episodes lasted a few seconds and rarely 1 min. He was investigated in a major teaching hospital for hypoglycaemia and cardiac dysrhythmia. EEG showed independent bitemporal abnormalities of slow and occasional sharp waves. MRI documented left-sided hippocampal atrophy. Nearly all the seizures were stopped with carbamazepine 400 mg daily. Following the diagnosis of temporal lobe epilepsy, he was made redundant from work.

A more complete clinical picture is expected to emerge now that MRI enables an in-vivo diagnosis of hippocampal sclerosis/atrophy (Figures 12.1 and 12.6).137,138

Figure 12.6. MRI findings in hippocampal sclerosis.

Figure 12.6

MRI findings in hippocampal sclerosis. Left: Coronal T1-weighted MRI scan showing right hippocampal sclerosis (arrow).

Demographic Data

Habitual hippocampal seizures typically begin in late childhood and early adolescence, mainly between 4 and 16 years of age.37,87,134,139 Onset before 4 years of age is considered rare,76 but certainly occurs140 (see also Figure 12.2). Seizures of MTLE-HS start earlier than in other forms of temporal lobe epilepsy.45 Both sexes are equally affected.134

MTLE-HS is the more common epileptic disease/syndrome, but its exact incidence and prevalence is unknown.4,5 It probably accounts for around 20% of patients with epilepsy and for 65% of patients with MTLE.8 Of patients whose epileptogenic region is sufficiently well localised to one temporal lobe to warrant temporal lobectomy, 60–70% have hippocampal sclerosis.141 The others have small alien tissue lesions, such as hamartomas or glial tumours, vascular and congenital malformations, and non-specific findings.

Similarly among children with temporal lobe epilepsy, 60% appear to have MTLE-HS.142 However, in a recent study of 63 children with new-onset temporal lobe epilepsy, only 18 (29%) had MTLE-HS. The others had either cryptogenic/idiopathic (34 children with normal neuroimaging findings and no significant past history) or developmental (10 children with long-standing, non-progressive temporal lobe tumours and malformations) temporal lobe epilepsy.143

Clinical Manifestations37,39,75,76,135,136

Patients with MTLE-HS usually have a previous history of initial precipitating incidents, including febrile seizures, trauma, hypoxia and intracranial infections, before 5 years of age and prior to the onset of their habitual non-febrile seizures.40,134,142,144–149 Complex focal seizures or generalised convulsions are the initial non-febrile seizures that attract medical attention. As a rule, they are preceded by simple focal seizures that may have been considered, sometimes for years, as normal phenomena. Classically, the onset of habitual seizures occurs after a latent period from the initial precipitating incidents. However, some patients have no identifiable initial precipitating incidents, and some have habitual seizures that begin immediately after the initial precipitating incidents.134

Epigastric aura, fear and oro-alimentary automatisms are the most common ictal symptoms.

Patient note

It starts with that strange stomach feeling and my panic, and then I pass out.

ILAE Classification and Definitions

The ILAE Commission (1989)1 classifies MTLE-HS among other temporal lobe epilepsies under the name ‘Amygdalohippocampal (mesiobasal limbic or rhinencephalic) seizures’ and describes them as follows:

“Hippocampal seizures are the most common form; the symptoms are those described in the previous paragraphs except that auditory symptoms may not occur. The interictal scalp EEG may be normal, may show interictal unilateral temporal sharp or slow waves, may show bilateral sharp or slow waves, synchronous or asynchronous. The intracranial interictal EEG may show mesial anterior temporal spikes or sharp waves. Seizures are characterized by rising epigastric discomfort, nausea, marked autonomic signs, and other symptoms, including borborygmi, belching, pallor, fullness of the face, flushing of the face, arrest of respiration, papillary dilatation, fear, panic, and olfactory-gustatory hallucinations.”1 The new ILAE diagnostic scheme classifies MTLE with hippocampal sclerosis in limbic epilepsies (page 21).2 The majority of expert contributors in the 2004 ILAE report consider MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity, but not a disease (despite common pathology).134

Clarifications on Nomenclature

MTLE-HS is usually described under the heading ‘MTLE’, though only 65% of patients have mesial temporal lobe seizures due to hippocampal atrophy. The remainder is due to mesial temporal lobe pathology other than hippocampal sclerosis.

The term ‘complex focal (partial) seizures’ has been erroneously used as a synonym of ‘temporal lobe epilepsy’.2 Ictal impairment of consciousness in focal epilepsies is a symptom of either neocortical or limbic seizures.

Simple Focal Seizures

Simple focal seizures are the commonest and most frequent seizure type in MTLE-HS, and occur in more than 90% of patients.35,37,38,40–43,45,65,70,76,78,133,136,150,151 The first symptom is always an aura. They mainly start with an ascending epigastric aura and less often with fear. Mental hallucinations and illusions of déjà vu and their variations occur, but not as commonly as in other extra-hippocampal epilepsies. Olfactory and gustatory hallucinations occur less often.

Simple focal seizures may be the only seizure type, though they often progress to complex focal seizures.

Ascending epigastric or visceral aura is by far the more common aura (around 80% of cases), and the most characteristic of all other ictal symptoms of simple hippocampal seizures.

Ictal fear is in a distant second most common aura (around 20–30% of cases), but is not specific to hippocampal seizures alone.

Dreamy states, 47 experiential phenomena, 28 intellectual aura, mental or psychic symptoms. These events occur less often than epigastric aura and fear, and the patient may also have other subjective ictal symptoms, such as mental illusions and hallucinations of déjà vu, depersonalisation and their variations.

Unspecified somatic sensations or olfactory and gustatory hallucinations may occur. Elementary or complex visual and auditory hallucinations do not occur.37

Urgency to urinate is exceptional and is associated with right-sided foci.63

Language impairment during simple focal seizures has not been examined thoroughly. Most patients are able to understand conversations fully, but they are unable to speak or carry on conversations; they answer monosyllabically or with movements of the head or hands.

Patient note

I know well what they say, but I can not speak or I reply in the simplest possible way with ‘yes’ or ‘no’ until I am back to normal again in a minute or so.

Simple focal seizures may be the only seizure type, sometimes for years, and can vary in duration from “a few seconds to rarely 1–2 minutes”. They may be entirely inconspicuous to the observer, though close relatives or friends are able to say when it happens.

Patient note

“He has it now”, the relative points out. The patient and the EEG confirms it, but nothing significant can be detected on the video record of events.

Simple focal seizures frequently progress to complex focal seizures with mainly oro-alimentary automatisms.

Complex Focal Seizures

In MTLE-HS, complex focal seizures usually emerge as a progression of simple focal seizures with gradual or abrupt impairment of consciousness that typically associates with oro-alimentary automatisms in about 70% of cases.35,37–43,45,65,70,76,78,133,136,150–153

The initial objective symptoms in this stage of impairment of consciousness are staring, motor restlessness or motor arrest, oro-alimentary automatisms and unforced head deviation. The patient has no recollection of this phase, but may still be responsive (70% of cases in one study).76 Gestural automatisms, other forms of automatisms, vocalisations and dystonic posturing may occur soon after. Hypersalivation (left sided) is exceptional.

Complex focal seizures last for 2–3 min, occur on average once or twice a week and usually appear in clusters of two or three. They may also occur during sleep and, in some women, they are exclusively or predominantly catamenial.

Oro-alimentary automatisms consist of lip smacking, chewing, swallowing, licking and tooth-grinding movements. They are often followed by simple gestural automatisms. Oro-alimentary automatisms are characteristic of MTLE only if preceded by epigastric aura, fear and mental symptoms of the ‘dreamy state’ of Jackson, alone or in combination.

Gestural automatisms consist of fiddling, fumbling, picking, tapping, patting or plucking, rubbing or scratching the face and other gestural movements.

Autonomic manifestations of any type are among the most frequent ictal symptoms of MTLE-HS.75,84–88,134 These manifestations include: pupillary dilatation and less commonly miosis;38,75 cardiovascular symptoms, mainly tachycardia and arrhythmias and less often bradycardia, asystole or hypertension;75,84,88–93 pallor and less commonly flushing;75 and changes in respiratory rate and depth, mainly in the late seizure phase.75

There are occasional reports of penile erection, or even ejaculation, and other sexual ictal manifestations.74,75

Lateralising Signs of Ictal Symptoms

Dystonic posturing occurs in 20–30% of patients and is contralateral to the side of seizure onset.38,136,154

Head deviation early in the seizure is usually ipsilateral to the seizure focus, but head deviation late in the seizure is contralateral and often a prelude to generalisation.38

Ictal or postictal aphasia and prolonged recovery is mainly seen following seizures in the dominant temporal lobe,38 while clear ictal speech and quick recovery mainly characterise seizures of the non-dominant temporal lobe.38,65

It is generally considered that unilateral automatisms are ipsilateral to the seizure onset.38

Although non-specific for right or left disease, impaired consciousness,76 motion arrest,76 escape automatisms76 and fear87,155 occur more often in patients with left rather than right mesial temporal sclerosis.

Hyperventilation during the seizure is rare and occurs in left mesial onset.76

Vocalisations,76 motor restlessness,76 staring,76 oral automatisms,38 pupillary dilatation,38 impaired consciousness38 or generalised rigidity38 do not predict side of origin.

Generalised Tonic Clonic Seizures

Secondarily GTCS are usually infrequent in patients receiving appropriate AEDs.134 They are not uniform in their clinical presentation, but are more stereotyped in their final phases than the initial clinical signs of generalisation.156 Some patients (probably around 10%) may never have GTCS.

Psychomotor Complex Focal Status Epilepticus

Psychomotor complex focal status epilepticus features particularly in untreated patients with temporal lobe epilepsy. It is less common than the absence status epilepticus of idiopathic generalised epilepsy, but its prevalence may be underestimated.157–159 It may be confused with transient global amnesia.160,161

Postictal Symptoms

Postictal symptoms of the mainly complex focal seizures in MTLE-HS are very frequent and often severe. They comprise mental and physical fatigue, drowsiness, headache, language aberrations, inability to concentrate and confusion of various degrees that may be severe and associated with automatic behaviour of which the patient may be amnesic.

Patient note

I am more concerned by what follows than the fit itself.

Definitions

Psychomotor (complex focal) status epilepticus is characterised by continuous or rapidly recurring psychomotor (complex focal) seizures that may involve temporal or extratemporal regions. Cyclic disturbance of consciousness is characteristic of psychomotor status epilepticus of temporal lobe origin. The differential diagnosis from complex focal status epilepticus of frontal lobe origin remains a challenge (Figure 12.11).162 In one-third of cases, a frontal lesion is revealed.163

Figure 12.11. Video EEG of a 43-year-old man during complex focal status epilepticus of frontal lobe origin.

Figure 12.11

Video EEG of a 43-year-old man during complex focal status epilepticus of frontal lobe origin. He was confused, disorientated in time and place, with bizarre behaviour, laughing and making inappropriate jokes. Note: (more...)

Neurological, Mental State and Behaviour

Neurological examination is usually normal; facial asymmetry contralateral to the epileptogenic zone may be apparent in some patients. Specific baseline and follow-up memory testing are necessary. The only clearly defined behavioural disturbance in MTLE-HS is a material-specific memory deficit, but this may also be seen in MTLE due to other mesial temporal lesions.134 Many other psychiatric and psychological problems, especially depression, have been reported to be more prevalent in MTLE-HS, but inadequate information exists to determine the extent to which these disturbances are a direct biological result of either the hippocampal sclerosis or the mesial temporal seizures, a non-specific biological result of brain injury, or a consequence of external psychological and social factors.134

Febrile Convulsions and Other Initial Precipitating Events

One-third of patients with MTLE-HS have a previous history of prolonged febrile convulsions and many others have a history of cerebral insults in early life.40,134,142,144–149

Mathern et al. (1995)147 found that 90% of patients have a history of complicated febrile convulsions or other initial precipitating events. The type of initial precipitating events and the patient’s age at which it occurred are related to the clinicopathological features. Thus, patients with a prolonged febrile seizure before 5 years of age are likely to have unilateral hippocampal atrophy and a good neurosurgical response.147,149

Aetiology

By definition all patients with MTLE-HS have hippocampal sclerosis. Conversely, hippocampal sclerosis is found in only two-thirds (65%) of patients with MTLE.8–11 Hippocampal sclerosis is predominantly unilateral in about 80% of neurosurgical series, contralateral hippocampal EEG discharges are common and one-third of patients have functional and structural extrahippocampal abnormalities.164,165 Other mesial temporal lobe structures may also be affected.75,165

‘Dual pathology’ is common166,167 and includes microdysgenesis, temporal lobe malformations of cortical development and indolent tumours, such as DNET.168 Patients with ‘dual pathology’ are more likely to have bilateral hippocampal atrophy.166,167

A genetic predisposition may be found in MTLE-HS, but this is not a uniform process:134

  • There is an increased incidence of a family history of febrile convulsions and epilepsy (mainly generalised epilepsies).145,169–171 The genetic predisposition for febrile seizures could be associated with especially severe seizures in some patients to produce hippocampal sclerosis and MTLE. Generalised epilepsy with febrile seizures plus (GEFS+) that leads to focal seizures could be an example of this.134
  • Usually, there is no increased family history of similar hippocampal seizures and hippocampal sclerosis does not occur in clinically unaffected twins.172 However, 18 of 52 asymptomatic individuals from 11 families with familial MTLE173 had left-sided (11 subjects) or bilateral (7 subjects) hippocampal atrophy; 14 of these individuals had classical MRI signs of hippocampal sclerosis.174 In these cases, the assumption is that the genetic defect may cause MTLE, which then leads to HS with or without febrile seizures.134 The role of genes has been recently reviewed.167,172
  • Sodium-channel defects in mice can cause hippocampal sclerosis, and it is possible that similar defects could have the same effect in humans leading to MTLE, with or without febrile seizures.134

Hippocampal Sclerosis

A hypocellular and gliotic (thus the word ‘sclerotic’) hippocampus is the pathological substrate of MTLE-HS. Hippocampal sclerosis presents with a unique pattern of cellular loss that is not found in other brain diseases.8

  • Selective regional hippocampal, mainly CA1, pyramidal cell loss occurs (> 30–50% of cases), predominantly involving the hilar region and dentate granule cells. Somatostatin and neuropeptide Y-containing hilar neurons are particularly susceptible. Preservation of the subiculum is pathognomonic.
  • Gamma-aminobutyric acid (GABA) neurons and terminals are relatively well preserved. CA2 are relatively spared.
  • Dispersion of dentate gyrus granule cells and sprouting of their axons (mossy fibres) that form aberrant monosynaptic excitatory feedback synapses on to the dendrites of granule cells.8,175,176.8,175,176
  • Changes in neuropeptide Y and somatostatin expression and reorganisation occur.177

Hippocampal Sclerosis and Temporal Lobe Epilepsy: Cause or Consequence?178

The cause of hippocampal sclerosis is unknown. There are two opposite views:

  1. The traditional concept is that prolonged febrile convulsions and other cerebral insults in early life cause hippocampal sclerosis and hippocampal epilepsy. This is because:
  • one-third of patients with MTLE-HS have a previous history of prolonged febrile convulsions and many others have a history of cerebral insults in early life40,142,144–148
  • MRI studies demonstrate that prolonged and focal febrile convulsions produce acute hippocampal injury evolving to hippocampal atrophy.179,180
  1. A current trend is that pre-existing hippocampal abnormalities predispose to febrile convulsions. If these are prolonged, they may cause further hippocampal damage evolving to mesial temporal sclerosis that may manifest with temporal lobe epilepsy.179–181 This view is supported because:
    • the estimated risk for developing temporal lobe epilepsy subsequent to prolonged febrile seizures is negligible, probably 1/75,000 children per year180,182
    • MRI studies suggest that there is a subtle, pre-existing hippocampal malformation that may facilitate febrile convulsions and contribute to the development of subsequent hippocampal sclerosis.179–181

Opinions and results are divided with probably half in favour of the first and the other half in favour of the second assumption.

Pathophysiology

Clinical note

How does this ‘atrophic’ and ‘sclerotic’ organ become one of the most powerful and common epileptogenic agents in human epilepsy?

The role of the hippocampus in epilepsy is due to synaptic remodelling and reorganisation of the hippocampal region. Enhanced sensitivity to glutamate may be important.183 These changes predispose surviving hippocampal neurons to abnormal hypersynchronous discharges that then propagate to other limbic and non-limbic structures, producing the manifestations of complex focal seizures.

Babb (1999),8 in an excellent review, on the subject concludes:

“The epileptic hippocampus has synaptic reorganisations, with GABA increasing the synchrony of firing thresholds and mossy fibres providing convergent excitation that then makes an otherwise cell-poor region fire a greater number of neurones for seizure initiation and propagation.” 8

Engel et al.,184 in a recent review, summarised the current state of our knowledge as follows:

“Most current parallel human/animal invasive research indicates that epileptogenesis in MTLE-HS is initiated by specific types of cell loss and neuronal reorganisation, which results not only in enhanced excitation, but also in enhanced inhibition, predisposing to hypersynchronisation. Also, evidence is found for more than one type of ictal onset, and individual seizures can demonstrate a transition from one ictal mechanism to another. In vivo and in vitro parallel, reiterative investigations in patients with MTLE-HS, and in rats with intrahippocampal kainate-induced hippocampal seizures, have revealed the presence of interictal epileptiform events, termed ‘fast ripples’, which appear to be unique in tissue capable of generating spontaneous seizures.” 184

See also other recent reports.175,184–191

Diagnostic Procedures

A clinical diagnosis of MTLE-HS demands confirmation with high-resolution MRI and EEG. CT brain scanning is unrewarding. Functional brain imaging provides insights in neurosurgical cases for which further information is required regarding lateralisation. Invasive intracranial recordings are necessary in exceptional cases.

Brain Imaging

MRI is the most important investigational tool.117,134

With improvements in MRI techniques, modern MRI scanners are of sufficiently high resolution to allow in-vivo visualisation of hippocampal sclerosis in all patients.137,138,192–195 Two-thirds of patients with MTLE have unilateral or bilateral hippocampal atrophy. In some patients, there is also evidence of other ‘dual pathology’, such as cortical malformations. In the other third, which by definition do not have MTLE-HS, MRI may be normal, but more usually reveals the structural cause responsible, such as a tumour (astrocytoma, ganglioglioma, dysembryoplastic neuroepithelial malformation), vascular abnormality (cavernous and venous angiomas, arteriovenous malformations), developmental abnormality (cortical malformations), atrophy or trauma. The sensitivity of MRI in the diagnosis of tumours and other lesions of the temporal lobe is estimated to be around 90%,137 but this will soon be exceeded.138 In straightforward cases of incontrovertible unilateral MTLE-HS confirmed by MRI, other tests may be unnecessary. However, it should be remembered that:

Clinical note

MRI evidence of hippocampal sclerosis is not necessarily related to seizure severity and may occur in individuals who never had seizures.174

18F-deoxyglucose positron emission tomography (FDG-PET) usually demonstrates ipsilateral hypometabolism if interictal or hypermetabolism if ictal (Figure 3.10). The abnormality of the affected temporal lobe appears much wider on FDG-PET than MRI.196,197 Interictal bitemporal PET hypometabolism of proven unilateral MRI hippocampal sclerosis is important and may reflect an advanced stage of the disease process. Half of these patients (53%) have bilateral independent seizure onset, longer disease duration and a poorer memory performance in the Wada test.198

[11 C] flumazenil PET is more sensitive than FDG-PET and a useful tool for investigating the hippocampal damage in vivo, even in patients with no remarkable hippocampal abnormalities on quantitative MRI.199 Results show a good correlation with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis.199 11C-flumazenil PET with correction for focal-volume effect200 reliably detects in-vivo reductions in central benzodiazepine receptor binding on the remaining neurons in the sclerotic hippocampi of patients with MTLE-HS.

SPECT is not as good for interictal studies, though ictal and postictal SPECT patterns are useful and reasonably reliable (Figure 3.8).201

New methodologies are nearly impossible to follow, and any reference to them made today would become obsolete within a few months.

Proton magnetic resonance spectroscopic imaging (1H-MRSI) of N-acetyl-aspartate, creatine and choline can accurately lateralise MTLE. It is less accurate in extratemporal epilepsy.118,202–207 1H-MRSI demonstrates a decreased relative resonance:intensity ratio of the neuronal marker N-acetylaspartate:creatine and phosphocreatine (NAA/Cr) in the affected hippocampus. 1H-MRSI may be valuable in neurosurgical cases with bilateral hippocampal atrophy. In one study, discriminant features associated with favourable surgical outcome were: (a) concordant 1H-MRSI lateralisation; (b) a greater side-to-side asymmetry of NAA/Cr; and (c) an absence of contralateral posterior NAA/Cr reduction.208 Recently, 31P nuclear magnetic resonance spectroscopic imaging, using very high strength magnets, has been shown to be useful.209

Clinical note

Important points on diagnostic procedures
• High resolution MRI provides in-vivo visualisation of hippocampal sclerosis in nearly all patients.
• A single routine interictal EEG is more likely to be normal (two-thirds of patients) than show the classical spike–wave focus in the anterior temporal lobe electrode (one-third of patients).

Interictal Electroencephalography

Routine interictal EEG shows the classical sharp or spike and slow-wave focus in nearly one-third of patients (Figure 12.4). Thus, in two-thirds of patients with MTLE-HS, a single, routine, 30-min EEG recording may be normal or show mild and non-specific abnormalities. The yield is doubled in repeat EEG, particularly when a longer sleep recording is made. Epileptiform abnormalities nearly always occur during prolonged monitoring.210

The characteristic interictal EEG abnormality consists of high-amplitude spike or sharp and slow wave complexes, either single or in clusters, localised in the anterior temporal electrode (Figure 12.4). These traditional ‘epileptogenic complexes’, when present, are unilateral in two-thirds of patients and occur independently, on the right or left, in the other third.75,210 They focus maximum in the basal derivations and they are best seen with sphenoidal, earlobe or true temporal derivations.211

Regional temporal lobe interictal runs of slow waves, which are of lateralising value, are recorded in about 50% of patients (Figure 12.4).123–125 Though not traditionally considered ‘epileptogenic’, runs of monomorphic slow waves occur more often than the spike itself.123–125

Bilateral GSWD do not occur, though occasionally bilateral fronto-polar spikes may be seen.

Ictal Electroencephalography

The ictal scalp EEG may be ‘normal’ or inconclusive in around 60% of cases at seizure onset in MTLE-HS.

A typical ictal EEG pattern consists of rhythmic, crescendo-like theta activity with decreasing frequency and increasing amplitude (Figure 12.2). It first appears over the affected temporal lobe, usually starts around 30 s prior to subjective or objective clinical seizure manifestations, and commonly spreads to the neighbouring and other regions (Figures 12.2 and 12.3).75 Rhythmic waxing-waning theta activity is also often encountered in scalp EEG, either lateralised with a maximum over temporal areas or not lateralised.134

Onset with regional attenuation of background rhythms and disappearance of the interictal spikes is less common.75 Such EEG flattening can occur either as a diffuse pattern or with predominance over one temporal region.

Unlike seizures from other locations, there are no fast spikes or fast rhythmic discharges in the ictal EEG of hippocampal seizures and spikes are relatively absent.

Simultaneous EEG and clinical onsets are uncommon.103 In the study of Williamson et al.,210 ictal scalp EEG changes were rarely detected at the time of clinical seizure onset, but lateralised build-up of rhythmic seizure activity during the seizure occurred in 80% of patients. However, in 13% of patients, the scalp EEG seizure build-up was contralateral to the side of seizure origin, as subsequently determined by depth EEG and curative surgery.

Invasive Electroencephalography

Concordant outpatient EEG and unilateral MRI hippocampal atrophy would obviate the need for in-patient EEG monitoring.193

Invasive EEG with depth implanted electrodes, subdural strips or grids and foramen ovale electrodes, alone or in combination, are now rarely needed, because precise localisation is usually possible following the improvements in non-invasive methodology, particularly MRI and functional brain imaging.134,192–195,212 However, they are still used when it is uncertain on which side mesial temporal ictal onset occurs or neocortical ictal onset has not been excluded. Direct recording from the hippocampus shows a ‘hypersynchronous hippocampal discharge pattern’ followed by low amplitude, high frequency, recruiting rhythm of more than 20 Hz.75,196 A low voltage, fast discharge is the second most common pattern.

Other Encephalographic Methodologies

Non-linear analysis of intracranial EEG activities can detect a ‘pre-ictal phase preceding the epileptic seizure.213

Whole-head magnetoencephalography may be a valuable non-invasive method; it distinguishes between mesial and lateral temporal seizure onset zones and identifies the spatial relationship of the structural lesion to the irritative zone.214

Differential Diagnosis

MTLE-HS needs to be differentiated from non-epileptic conditions and from seizures arising from other brain locations (Table 12.1).

Table 12.1

Table 12.1

Mesial versus lateral temporal lobe epilepsy

  • Non-epileptic conditions. The diagnosis of hippocampal seizures should be suspected from their very brief duration, the ascending character of the epigastric sensations, the occasional nocturnal appearance and often an associated feeling of depersonalisation. However, simple focal seizures of epigastric aura and ‘panic attacks’ are unlikely to raise suspicion of epilepsy in either the patient or the general physician (Figure 12.2). These patients are often investigated for gastroenterological and psychological disorders215 or hypoglycaemia until more salient seizure features appear with the development of complex focal seizures and secondarily GTCS. Patients are often reassured by normal relevant tests or told that their symptoms are the result of anxiety. It is rare, at this stage, that a general physician would request an EEG, but again, if this normal (as is the case in two-thirds of patients), a diagnosis of stress-related events would be reinforced.
Clinical note

Pseudo-seizures may be difficult to differentiate. An increase in serum prolactin level postictally may be helpful in differentiating between epileptic seizures and ‘pseudo-seizures’.216

  • Mesial temporal epilepsy with aetiologies other than hippocampal sclerosis: The differential diagnosis of hippocampal from other MTLE is practically impossible without MRI, with the possible exception of olfactory-gustatory hallucinations, which may be more often associated with tumoural MTLE.134
  • Hippocampal versus other temporal lobe seizures: The epigastric aura and early oro-alimentary automatisms predominate in MTLE compared with other neocortical temporal lesions. Conversely, MTLE-HS is unlikely when seizures manifest with early focal motor, somatosensory, visual or auditory ictal symptoms, frequent secondarily GTCS or occur in patients with neurological or cognitive deficits other than memory impairment.
  • Hippocampal versus mesial familial temporal lobe epilepsy (MFTLE): The main differentiating features in favour of mesial familial temporal lobe epilepsy are:
    • – onset in teenage or early adult life and familial occurrence
    • – no febrile convulsions or other initial precipitating events
    • – no ictal symptoms of rising epigastric aura
    • – mild and infrequent seizures that may remit
    • – usually normal MRI.
  • Typical absence seizures are more likely to be misdiagnosed as complex focal seizures than vice versa.

Prognosis

Despite the high prevalence and known pathology, the prognosis and many other important aspects of MTLE-HS are largely unknown.

Neurosurgical Series

The neurosurgical cases show a specific clinical pattern.37,39,75,76,135,136 Seizures are initially relatively well controlled with AED for several years (silent period).134 Seizures relapse in adolescence or early adulthood, occurring several times per week or usually several times per month, and become refractory to medication. Memory and behavioural disturbances may occur. Neurosurgery is probably mandatory at this stage, because spontaneous remission is unlikely, drugs do not work and polypharmacy makes it worse.

Community Studies

Community-based studies have shown that 10–40% or more of patients with epileptic seizures of temporal lobe origin may go into remission.130 I have tried to understand and give a gross estimate of the prognosis in MTLE-HS by reviewing the literature, my database and asking other epileptologists. I reached the following conclusions, which may roughly indicate the spectrum of MTLE-HS.

  • About 50% are intractable cases that require neurosurgical evaluation and management, though only 10% or less of these patients benefit.
  • Around 30% of patients are relatively well controlled with appropriate AEDs. These patients may have simple or complex focal seizures, and occasional GTCS that interfere with their daily life, but not to a degree that makes it intolerable. They are handicapped, but they may still function adequately within their families and their jobs. How many of these patients need or would accept neurosurgical intervention is uncertain.
  • The other 20% of patients are otherwise normal, with occasional simple or complex focal seizures for which they may be treated or untreated. These patients may come to our attention because of an occasional GTCS, a lengthy or severe complex focal seizure or an EEG performed for reasons other than epilepsy.

Is Hippocampal Epilepsy a Progressive Disease?

Whether hippocampal epilepsy is a progressive disease is a highly debatable and controversial matter.134 In most patients, MTLE-HS may not have a progressive course as indicated by community studies and clinical experience. Further, hippocampal atrophy remains stable over the duration of temporal lobe onset seizure disorders.217 Miller et al. (2000)218 used proton MRSI to measure NAA/Cr ratios in the temporal lobes of five consecutive children with newly diagnosed temporal lobe epilepsy compared with another five children of similar age that suffered from intractable temporal lobe epilepsy. They found that the severity of the neuronal dysfunction in children with newly diagnosed temporal lobe epilepsy was at least as severe as in those with intractable temporal lobe epilepsy, implying that the neuronal abnormalities occurred before the clinical manifestations.

The neurosurgical patients may be derailed cases of MTLE-HS. This may be a common, but not a defining situation. Engel et al. (1997)37 favour a progressive course for the neurosurgical cases for the following reasons:

  • Cell death and neuronal reorganisation probably continue with recurrent seizures.8,147
  • There is a long silent period between the time risk factors (febrile convulsions) appear and the onset of habitual seizures. Similarly, medical intractability may develop long after relevant control of seizures with medication.40
  • Persistence of simple focal seizures (auras) after extensive mesial temporal lobe resection is correlated with the duration of epilepsy before surgery, and may indicate that wider brain areas than the sclerotic hippocampus are epileptogenic.37

Management

Medical treatment of MTLE-HS with AEDs may be relatively effective in 80% of patients; for the other 20% and probably many more with intractable seizures, neurosurgical resection of the offending epileptogenic region is usually successful.

Antiepileptic Drug Treatment

Drug treatment is similar to that for any other type of focal seizure.

Of the older drugs, carbamazepine or phenytoin monotherapy is the most appropriate. Carbamazepine is superior for controlling focal seizures in more than 70% of patients (10% of the patients develop idiosyncratic reactions).

Phenytoin is as effective as carbamazepine, but its use is falling dramatically in developed countries, mainly because of chronic toxicity.

Phenobarbitone and primidone are less efficacious and have been practically eliminated from use, mainly because of their adverse effects on cognition.

Clobazam, though often highly beneficial in selective cases, is rarely used as continuous AED treatment. Clobazam is, however, worth trying in patients who do not respond or those who develop side effects, such allergic reactions to other drugs.

Valproate, though a superior drug for generalised epilepsies, is inferior in focal epilepsies with significant concerns in the treatment of women. The new AEDs, in order of my preference, are as follows:

  1. Oxcarbazepine, possibly of equal efficacy with carbamazepine but with fewer idiosyncratic reactions, is probably the AED of first choice in monotherapy. Its use in polytherapy is less advantageous.
  2. Levetiracetam is becoming increasingly popular. It is the first choice AED in adjunctive treatment, because of its combination of high efficacy, comparative poverty of adverse reactions, lack of drug–drug interactions, novel mechanism of action and rapid titration.
  3. Lamotrigine may work extremely well in some patients. It is one of the best drugs in terms of lack of cognitive adverse effects, but its efficacy is low and idiosyncratic reactions, which may be fatal in exceptional cases, are a realistic threat.
  4. Topiramate is the most efficacious of the new drugs, but significant concerns about serious and multiple adverse reactions hinder its use.
  5. Zonisamide is used extensively in Japan and may become more popular in other countries.
  6. Tiagabine is being used cautiously, because of moderate efficacy and adverse reactions.
  7. Gabapentin is largely ineffective, even in high doses.

If treatment with one or two of the main AEDs fails, the chances of achieving medical control in MTLE-HS are negligible. Polypharmacy with more than two or three AEDs, even when rational, will add more misery, memory problems and drowsiness rather than any benefit.219,220 These patients, even in childhood,221 need urgent evaluation for neurosurgical treatment for which they are the best candidates of all symptomatic focal epilepsies, and the most likely to have excellent and sustained benefit.

Neurosurgical Treatment

Clinical note

With early surgical intervention, patients with MTLE-HS have an excellent chance of cure and a subsequent normal life.134

MTLE-HS responds well to temporal lobe surgery, regardless of whether resection of the anterior two-thirds of the temporal lobe or a selective amygdalohippocampectomy is performed.37,75,134,167,222–225 Cognitive outcome is better after amygdalohippocampectomy, which is the procedure of first choice when pathology is confined to mesial structures.76

Important note

After anterior temporal lobe resection with hippocampectomy, around 60% of patients will be seizure free even after all AEDs have been withdrawn, 20% will need to continue with AEDs and may have reduced numbers of seizures, 10% will have no benefit, and 10% may have neurosurgical complications and get worse. Significant neurosurgical complications rarely occur.226

There is no consensus as to how much of the hippocampus should be removed.134 It has not yet been determined whether all patients require a maximal hippocampal resection. The amount of hippocampal resection is often determined intraoperatively by the extent of electrocorticographic interictal epileptiform abnormalities, allowing for sparing of possibly functionally important hippocampus.227

Important note

In general, “the benefits of anteromesial temporal lobe resection for disabling complex partial seizures of temporal lobe epilepsy is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable”.131,132

The quality of life following surgical treatment depends on psychosocial factors, and pre-existing vocational and interpersonal skills.228 Attention to psychosocial and possibly memory deficits is of paramount importance. Appropriate rehabilitation following successful surgery is needed; some patients find it difficult to adjust to a new life ‘without epilepsy’.

Clinical note

Interesting historical note
It is amazing that MTLE-HS, the most frequent and provocative focal epilepsy escaped recognition until around 1953.229 Until then, focal seizures were attributed to damage of neocortical brain regions for which excisional neurosurgery was utilised. The atrophic hippocampus was ignored.

Mesial Temporal Lobe Epilepsy Defined by Specific Aetiologies Other than Hippocampal Sclerosis

Clinical note

In MTLE with aetiologies other than hippocampal sclerosis,37,39,75,76,135,136 seizure symptomatology is the same irrespective of cause and location within the mesial temporal lobe structures. MRI commonly identifies structural causes.

Clinical Manifestations

The overall view is that seizure symptomatology is the same irrespective of cause and location within the mesial temporal lobe structures. Thus, seizures of hippocampal sclerosis are considered indistinguishable from those caused by other lesions in the mesial temporal lobe. Their differentiation is also practically impossible with surface EEG. High resolution MRI provides anatomical evidence of localisation in nearly all symptomatic cases. The sensitivity of MRI in the diagnosis of tumours and other lesions of the temporal lobe is estimated to be around 90%,137 but this will soon be exceeded.

Aetiology

Structural causes comprise malignant and benign tumours (astrocytomas, gangliogliomas, dysembryoplastic neuroepithelial malformations), vascular abnormalities (cavernous and venous angiomas, arteriovenous malformations), malformations of cortical development, trauma and other injuries, viral and other infective agents, and cerebrovascular disease.7,143

Management

Drug treatment is similar to that for any other type of focal seizure.

Neurosurgical intervention often provides an excellent chance of cure and a subsequent normal life in certain pathological conditions of LTLE.

Lateral Temporal Lobe Epilepsy

Lateral temporal lobe epilepsy 1,76,113,136 is neocortical as opposed to MTLE, which is limbic.

Clinical Manifestations

Simple seizures of LTLE are characterised by auditory hallucinations (ringing, humming, clicking, unspecified noises) or illusions, vestibular phenomena, mental illusions and hallucinations of the dreamy states and visual misperceptions. Language disturbances occur in dominant hemisphere focus.

Motor ictal symptoms include clonic movements of facial muscles, grimacing, finger and hand automatisms, dystonic posturing of an upper extremity, leg automatisms, restlessness and unformed vocalisations. Rotation of the whole body is common and of value in differentiating LTLE from MTLE.

Symptoms may progress to complex focal seizures by spreading to mesial temporal or extratemporal structures. Impairment of consciousness is not as pronounced as in MTLE.76

See also lateral (autosomal dominant) familial temporal lobe epilepsy (see page 355).

Aetiology

The structural causes of LTLE are similar to those of MTLE apart from hippocampal sclerosis.

Diagnostic Procedures

MRI often determines structural causes of LTLE (Figure 12.7).

Figure 12.7. Axial proton density-weighted MRI showing left temporal lobe cavernoma in a patient with LTLE.

Figure 12.7

Axial proton density-weighted MRI showing left temporal lobe cavernoma in a patient with LTLE. Figure courtesy of Professor John S Duncan and the National Society for Epilepsy MRI Unit.

Scalp interictal EEG shows unilateral or bilateral midtemporal or posterior temporal spikes (Figure 12.5).1,76

Differential Diagnosis

Lateral temporal lobe seizures usually lack the features commonly exhibited in MTLE, as detailed in Table 12.1.

Gil-Nagel and Risinger (1997)136 compared the ictal features of 16 patients with hippocampal epilepsy with those of 19 patients with extra-hippocampal temporal lobe seizures associated with a small tumour in the lateral or inferior temporal cortex. The association of a prior history of febrile convulsions, epigastric aura and early oral automatisms with hippocampal epilepsy was statistically significant. Conversely, an aura with experiential content and early motor involvement of the contralateral upper extremity without oral automatisms was significantly associated with extra-hippocampal temporal lobe epilepsy. Arrest reaction, vocalisation, speech, facial grimace, postictal cough, late oral automatisms and late motor involvement of the contralateral arm and hand occurred with similar frequency in both groups.

Foldvary et al. (1997)113 compared eight patients with LTLE and 20 patients with MTLE. MTLE patients were younger at the onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications or head injury. LTLE seizures lacked the features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation and postictal cough or sigh.

The ILAE (1989) Definition for Lateral Temporal Lobe Seizures Is:

“Simple seizures characterized by auditory hallucinations or illusions or dreamy states, visual misperceptions, or language disorders in case of language dominant hemisphere focus. These may progress to complex focal seizures if propagation to mesial temporal or extratemporal structures occurs. The scalp EEG shows unilateral or bilateral midtemporal or posterior temporal spikes which are most prominent in the lateral derivations.”1

Elger (2000)76 reported that, in LTLE, auras are rare and variable (15%). Motor ictal symptoms include clonic movements of the facial muscles, grimacing, finger and hand automatisms, dystonic posturing of an upper extremity, oro-alimentary automatisms, leg automatisms, restlessness and unformed vocalisations. He emphasised that rotation of the whole body is frequent and of value in differentiating LTLE from MTLE. Eye blinking, aggressive behaviour, dystonic posturing, early or late oro-alimentary automatisms and hypersalivation, which are common in MTLE, did not occur in epilepsy of non-mesial onset. Further, impairment of consciousness was not as pronounced as in MTLE.

Management

Drug treatment is similar to that for any other type of focal seizure.

Neurosurgical treatment provides an excellent chance of cure and a subsequent normal life in certain pathological conditions of LTLE.

Frontal Lobe Epilepsies

Frontal lobe epilepsies manifest with seizures originating from a primary epileptic focus anywhere within the frontal lobe. The clinical and EEG manifestations vary greatly and depend on the origin and spread of the epileptogenic focus.230–240 The frontal lobe occupies 40% of the cerebral cortex and is the largest of the brain lobes. On the basis of cyto-architectural and functional studies, the frontal lobe can be subdivided into the primary motor cortex, premotor cortex, prefrontal cortex, and the limbic and paralimbic cortices,236 with distinct cortico-subcortical organisations and immense connections with the temporal and parietal cortices.233,241 Complex and varied patterns in the spread of seizure discharges explain the variability in the clinical and EEG manifestations of frontal lobe seizures.232,242 Also, exact localisation is often hindered because of the rapid propagation of seizures within the frontal lobe from and to extrafrontal areas. It is difficult to assign the origin of seizures with pre- and post-central symptomatology to the frontal or parietal lobe. Such overlap to adjacent anatomical regions also occurs in opercular epilepsy.1

Seizures arising from the primary motor cortex and the supplementary motor area (SMA; Figures 12.8 and 12.9) have been relatively well defined, but seizures generated in other regions of the frontal lobe are less well specified.

Figure 12.8. MRI in two patients with symptomatic frontal lobe epilepsy.

Figure 12.8

MRI in two patients with symptomatic frontal lobe epilepsy. Left: Coronal FLAIR MRI showing focal cortical dysplasia in the supplementary motor area of the left frontal lobe. Note the tail extending down towards the frontal horn of (more...)

Figure 12.9. Hypermotor seizure of the sensorimotor supplementary area.

Figure 12.9

Hypermotor seizure of the sensorimotor supplementary area. Sample from one of 10 stereotypical hypermotor seizures recorded during an all-night video EEG. Note the abrupt and explosive character of the seizure, which lasted for only (more...)

Demographic Data

Frontal lobe epilepsies may start at any age and both sexes are equally affected. They are probably rare, accounting for about 1–2% of all epilepsies, though they are second in prevalence, after temporal lobe epilepsies, in neurosurgical series. In a prospective community-based study,243 the prevalence of frontal seizures (22.5%) among focal epilepsies was comparable to that of temporal lobe (27%) and central sensorimotor (32.5%) localisation. Seizure onset from the frontotemporal (5.6%), parietal (6.3%) or posterior cortex (6.3%) was less common.243

Clinical Manifestations

According to their origin within the frontal lobe, various seizure patterns have been recognised though multiple frontal areas may be involved. Rapid and specific seizure types may not be discernible.1 Motor manifestations are more common and the most characteristic ictal symptom occurring in 90% of seizures.

The following are the most common frontal lobe seizures.

Seizures from the Motor Cortex

Seizures from the motor cortex are mainly simple focal motor seizures. Symptoms depend on the side and topography of the area involved. Focal motor seizures (with or without march) originate from the contralateral precentral gyrus. In the lower pre-Rolandic area, there may be speech arrest, vocalisation or dysphasia, tonic-clonic movements of the face on the contralateral side, or swallowing. In the paracentral lobule, tonic movements of the foot may occur, which may be ipsilateral or contralateral. Seizures often progress to secondarily generalisation. Postictal Todd’s paralysis is frequent.

Simple Focal Motor Clonic or Tonic-Clonic Seizures with or without Jacksonian March

These seizures manifest with localised, rhythmic or arrhythmic, clonic movements that may affect the thumb only, the thumb and ipsilateral side of the lips, the hand, the whole arm or any other body part contralateral to the focus. Distal segments are more frequently affected than proximal segments. The hand (mainly the thumb) and face (mainly the lips) are preferentially affected because of their larger cortical representation (homunculus of Penfield). These ictal motor manifestations may remain highly localised for the whole of the seizure or march in an ordinary anatomical fashion to neighbouring motor regions, which constitute the classical Jacksonian (or Bravais-Jackson) seizure.

Patient note

Usually there are a few jerks of the right corner of my mouth and the right thumb. That is all. However, the jerks may become more intense and spread gradually to my eye and my fingers on the same side. Then my elbow and shoulder also start jerking violently and this may also go to my leg. The whole right side of my body is jerking and jerking, and there is nothing I can do before this stops suddenly or I lose consciousness and I have whole body convulsions.

Myoclonic seizures that may be unilateral or bilateral are predominantly facial or distal in the limbs. Epilepsia partialis continua of Kozhevnikov is one type of myoclonic seizure.

Tonic postural motor seizures associated with clonic movements are asymmetric, unilateral or bilateral.

ILAE Classification and Definitions

The seizures and some syndromes of frontal lobe epilepsy have been well described in the 1989 ILAE classification among the localisation-related (focal, local, partial) epilepsies and epileptic syndromes, and defined as follows: 1

“Frontal lobe epilepsies are characterized by simple partial, complex partial, secondarily generalized seizures or combinations of these. Seizures often occur several times a day and frequently occur during sleep. Frontal lobe partial seizures are sometimes mistaken for psychogenic seizures. Status epilepticus is a frequent complication.

General characteristics

Features strongly suggestive of the diagnosis include:

1. Generally short seizures.

2. Complex partial seizures arising from the frontal lobe, often with minimal or no postictal confusion.

3. Rapid secondary generalization (more common in seizures of frontal than of temporal lobe epilepsy).

4. Prominent motor manifestations which are tonic or postural.

5. Complex gestural automatisms frequent at onset. 6. Frequent falling when the discharge is bilateral. A number of seizure types are described below; however, multiple frontal areas may be involved rapidly and specific seizure types may not be discernible.

Supplementary motor seizures. In supplementary motor seizures, the seizure patterns are postural, focal tonic, with vocalization, speech arrest, and fencing postures.

Cingulate. Cingulate seizure patterns are complex partial with complex motor gestural automatisms at onset. Autonomic signs are common, as are changes in mood and affect.

Anterior frontopolar region. Anterior frontopolar seizure patterns include forced thinking or initial loss of contact and adversive movements of head and eyes, with possible evolution including contraversive movements and axial clonic jerks and falls and autonomic signs.

Orbitofrontal. The orbitofrontal seizure pattern is one of complex partial seizures with initial motor and gestural automatisms, olfactory hallucinations and illusions, and autonomic signs.

Dorsolateral. Dorsolateral seizure patterns may be tonic or, less commonly, clonic with versive eye and head movements and speech arrest.

Opercular. Opercular seizure characteristics include mastication, salivation, swallowing, laryngeal symptoms, speech arrest, epigastric aura, fear, and autonomic phenomena. Simple partial seizures, particularly partial clonic facial seizures, are common and may be ipsilateral. If secondary sensory changes occur, numbness may be a symptom, particularly in the hands. Gustatory hallucinations are particularly common in this area.

Motor cortex. Motor cortex epilepsies are mainly characterized by simple partial seizures, and their localization depends on the side and topography of the area involved. In cases of the lower prerolandic area there may be speech arrest, vocalization or dysphasia, tonic-clonic movements of the face on the contralateral side, or swallowing. Generalization of the seizure frequently occurs. In the rolandic area, partial motor seizures without march or jacksonian seizures occur, particularly beginning in the contralateral upper extremities. In the case of seizures involving the paracentral lobule, tonic movements of the ipsilateral foot may occur as well as the expected contralateral leg movements. Postictal or Todd’s paralysis is frequent.”1 “In frontal lobe epilepsies, the interictal scalp recordings may show (a) no abnormality; (b) sometimes background asymmetry, frontal spikes or sharp waves; or (c) sharp waves or slow waves (either unilateral or frequently bilateral or unilateral multiobar. Intracranial recordings can sometimes distinguish unilateral from bilateral involvement.

In frontal lobe seizures, various EEG patterns can accompany the initial clinical symptomatology. Uncommonly, the EEG abnormality precedes the seizure onset and then provides important localizing information, such as: (a) frontal or multilobar, often bilateral, low-amplitude fast activity, mixed spikes, rhythmic spikes, rhythmic spike waves, or rhythmic slow waves; or (b) bilateral high amplitude single sharp waves followed by diffuse flattening. Depending on the methodology, intracranial recordings may provide additional information regarding the chronologic and spatial evolution of the discharges; localization may be difficult.” 1 Frontal lobe epilepsies other than epilepsia partialis continua and Kozhevnikov-Rasmussen syndrome have not been detailed in the new ILAE diagnostic scheme. 10

Seizures from the Supplementary Sensorimotor Area

Seizures from the SMA have distinct and characteristic clustering of symptoms, and are usually stereotyped (Figure 12.9).244–249

Hypermotor seizures250 of bizarre bilateral, asymmetric tonic posturing and movements

The characteristic hypermotor seizure of SMA consists of sudden and explosive, bilateral and asymmetric tonic posturing of limb girdles at shoulder and pelvis often with contraversion of the eyes and head, vocalisation or speech arrest.

‘Fencing posturing’251 is the best known descriptive term for these SMA seizures, though it may not be common.249 In fencing posturing, one arm is raised and semi-extended above the head, while the other remains by the body semi-flexed at the elbow. Bilateral asymmetrical posturing is the most common.

M2E posture is another term used to describe flexion of the elbow of one arm, abduction of the shoulder to 900, with associated external rotation.19 The head looks at the postured hand, and the opposite arm shows slight flexion. The leg ipsilateral to the involved arm extends, while the opposite leg flexes at the hip and knee.

Clinical note

Posturing is extremely variable among patients with SMA seizures, but it is stereotypical for each individual patient.

This variability of hypermotor seizures is reflected well by other descriptive terms of SMA seizures, such as:

  • – complex gestural automatisms,
  • – extreme motor restlessness,
  • – complex motor automatisms and agitation,
  • – frenetic complex motor automatisms of both arms and legs,
  • – intensely affective vocal and facial expression associated with powerful bimanual-bipedal and axial activity,
  • – repetitive rhythmical and postural movements accompanied by bizarre vocalisation,
  • – complex motor automatisms with kicking and thrashing, complex and global gesticulations.
Clinical note

Somatosensory or other ill-defined auras (not epigastric), vocalisations and speech arrest are common ictal manifestations of SMA seizures.

Somatosensory auras are described by more than half and probably about 80%253 of patients, mainly at onset. Unilateral somatosensory sensations usually accurately predict contralateral lateralisation.254 Cephalic sensations are probably more common.253 Auras are described as:

Patient note

pressure on the chest, difficult to breathe, floating away, paraesthesia of a hand, dizziness and light headedness, cephalalgia or electrical sensation in the head, discharge in the whole body, sensation of body heat, feeling of coldness or heat in the back and the head, vertebral column shivering, moving outside oneself, crawling sensation in both, one leg or somewhere in the body.250,253,255,256

Important note

Epigastric auras do not occur.

Vocalisations

One-third of patients manifest with vocalisations that may vary from a brief deep breath or air expiration and palilalic vocalisations to the most bizarre, loud and scaring noises.

Definition of Hypermotor Seizures

Hypermotor seizures consist of “complex, organised movements which affect mainly the proximal portions of the limbs and lead to a marked increase in motor activity. Consciousness may be preserved. They are most frequently associated with frontal lobe epilepsy”.250,252

Speech arrest is a well-documented and frequent ictal manifestation. Pure paroxysmal speech arrest without other motor activity is exceptional.

Consciousness is usually well preserved; as a rule, these are simple focal seizures.

Other characteristics of seizures from the SMA are:

  • abrupt onset and abrupt termination
  • nocturnal circadian distribution; rarely occur in awake states
  • high frequency, sometimes many per night
  • lack of postictal confusion.

Seizures from Other Frontal Lobe Regions

Seizures from other frontal lobe regions are less common and are, topographically: cingulate, anterior frontopolar, orbitofrontal, dorsolateral and opercular seizures.1

Other Frontal Lobe Seizures of Particular Clinical Interest

The following frontal seizures are of particular clinical interest:

  1. ‘Frontal absences’ are similar and often indistinguishable from generalised absence seizures in their clinical and EEG manifestations (Figure 12.10).257,258
  2. Seizures characterised by unusual symptoms of ‘forced thinking’ and ‘forced acts’. The patient is forced into an obsessive thought (forced thinking) associated with a fairly well-adapted attempt to act on this thought (forced acts),49,49,51,51 with ‘eye-directed automatisms’ and ‘pseudo-compulsive behaviour’. These seizures emanate from the dorsolateral intermediate frontal lobe. French investigators vividly described the seizures as follows:232,238,259–261
Figure 12.10. Typical absence seizures of late onset due to frontal lobe glioma.

Figure 12.10

Typical absence seizures of late onset due to frontal lobe glioma. Left: Brain imaging showing a right-sided frontal glioma in a woman who started having absences at 28 years of age (1989). Middle right and left: Initially, the EEG (more...)

“Gaze and gestures of the upper limbs appear to be attracted by some object in the immediate environment, which orients a pseudo-intentional sequence of catching, touching, putting in order, or playing with the hands. Aggressive facial expression and complex vocalisation (menaces, insults, obscenities) precede a sequential gestural pattern such as standing up, then running around the table, spitting, tapping on the table, seemingly speaking to somebody; or jumping or pedalling movements with rhythmic joyful vocalisation. Their onset is often marked by alternating head deviations as if oriented towards an external stimulus… In other cases, they consist of much more complex and bizarre gesticulations, seemingly aimless, or apparently running away from some frightening situation, possibly as a reaction to ‘unconscious’ hallucinations. Often occurring during sleep, they are characterised by a facial expression of fear or terror, a powerful vocalisation (screaming), agitation of the upper limbs as if struggling or tearing out something, manipulation of the genitals accompanying pelvic movements, pedalling movements, or kicking.”232,238,259–261

Tonic deviation of the eyes preceding head deviation (frontal eye field involvement) may occur independently or in association with these strange symptoms.232,238,261

Patient note

The patient is compulsively ‘forced to fix on something with the eyes’, ‘the brain commands him to do something that he should not do’, ‘a sensation of being forced to open the eyes’. This is often associated with forced bizarre actions of hypermotor seizures.

A 30-year-old man, holder of a karate black belt, had a cluster of 30–50 such seizures while dozing in the waiting room of my clinic. Each seizure, which lasted for 10–15 s, was of sudden onset and termination. His facial expression was very aggressive and he would perform various karate acts, often kicking or punching objects in the office (without damaging them), with simultaneous and irregular roaring and other vocalisations. Immediately, after each attack, he would go back and sit in his chair, and fully aware of what was happening he would then apologise, “I can not resist doing this. It will be OK after a while”, before jumping off again to perform a similar enforced act. The staff and the other patients were terrified and maintained a safe distance from him, while I had to put on a brave face to approach him until he recovered.

c. Gelastic seizures of frontal lobe origin. 101,262 There are around 15 well-documented cases of gelastic seizures originating from the frontal lobe. Onset is usually before the age of 6 years, but may start in adulthood in one-third of patients. Most lesions commonly involve the cingulate gyrus. Laughter is described as unnatural and mirthless. The duration of the seizure is brief, lasting from less than 30 s to less than 2 min. Other types of seizures may predate or follow the gelastic attacks.

See also hypothalamic (gelastic) epilepsy on page 193.

d. Negative motor seizures manifest with ictal loss of localised muscle power or inability to produce a voluntary movement.

Focal Status Epilepticus of Frontal Lobe Origin

Focal (non-convulsive) status epilepticus of frontal lobe origin is of undetermined prevalence.162,163 It manifests with prolonged impairment of consciousness and inappropriate behaviours (Figure 12.11). Symptoms fluctuate in intensity and severity over time. Concurrent turning of the head and focal jerking may occur. It commonly ends with GTCS. Ictal EEG shows repetitive frontopolar, frontocentral and frontotemporal epileptiform discharges with unilateral emphasis. It is difficult to differentiate from frontal or idiopathic absence status epilepticus without EEG (Figure 12.11).

Thomas et al. (1999)163 described two types of frontal lobe status epilepticus. The first and more common type manifests with mood disturbances with affective disinhibition or affective indifference, which are associated with subtle impairment of cognitive functions without overt confusion. The EEG shows a unilateral frontal ictal pattern and normal background activity. In the second type, impaired consciousness is associated with bilateral, asymmetric frontal EEG discharges on an abnormal background. The response to intravenous benzodiazepines is poor, while intravenous phenytoin successfully controls seizures in most patients.163

Aetiology

Frontal lobe epilepsies may be symptomatic, probably symptomatic or idiopathic. Two-thirds of patients in neurosurgical series are symptomatic261 as a result of malformation of cortical development (57.4%), tumours (16.4%), and trauma and other lesions (26.2%).263

Of the idiopathic forms, autosomal dominant, nocturnal, frontal lobe epilepsy is detailed in Chapter 11.

Diagnostic Procedures

High resolution brain MRI is mandatory. This reveals abnormalities in around two-thirds of patients.

Functional neuroimaging and magnetoencephalograpy are important for localisation.264

Ictal and interictal surface EEG has a notoriously low yield. Normal EEG is often misinterpreted as evidence of non-epileptic attacks.

Serum prolactin concentration (> 700 μU/ml) may be raised after frontal lobe seizures, with or without secondarily GTCS. However, failure of prolactin levels to rise does not help in the clinical differentiation of frontal lobe complex focal seizures from psychogenic attacks.

MRI

High resolution MRI detects abnormalities in 67% of patients with frontal lobe epilepsy as opposed to 79% in temporal lobe epilepsy. The overall sensitivity and accuracy of MRI is around 50% in neurosurgical series, but will become higher with new MRI technologies (Figure 12.8). This figure is similar to qualitative linear (routine) analysis of FDG-PET. Quantitative normalised analysis of FDG-PET scans have 96% sensitivity and 74–78% accuracy, and also detects 81% of abnormalities in non-lesional cases.265

MRS may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.266

Electroencephalography

Interictal and ictal surface EEG is often unhelpful in the diagnosis of frontal lobe epilepsies. They are often normal (50–60% of cases), particularly when seizures originate from the medial frontal regions. The EEG of patients with lateral seizures is far more revealing than that of mesial frontal seizures (Figure 12.11). Prolonged video EEG recording increases the EEG yield.267

Patient note

The video EEG of one of my patients with tens of clinical SMA seizures was entirely normal over two nights, except for a single, left frontal, giant sharp and slow wave that occurred only once.

Important note

The EEG, both interictal and ictal, is usually normal in seizures originating from the mesial frontal regions, a factor that contributes to misdiagnosis.1,239,263,268

If abnormal, interictal EEGs may show background asymmetry, frontal spikes or sharp waves (either unilateral or frequently bilateral or unilateral multilobar).1 Generalised discharges of 3-Hz spike–waves may occur with or without evidence of secondary bilateral synchrony.

Abnormal Ictal EEG Patterns Consist of
  • frontal or multilobar, often bilateral, low amplitude, fast activity, mixed spikes, rhythmic spikes, rhythmic spike waves, or rhythmic slow waves (Figure 12.12). Ictal, fast, rhythmic paroxysms may be of very high frequency (> 50 Hz) and low amplitude requiring specialised recording systems with fast sampling rates and high sensitivity.269
  • bilateral high amplitude single sharp waves followed by diffuse flattening. sUncommonly, this EEG abnormality precedes the seizure onset providing important localising information.1,270
Figure 12.12. Top: Interictal EEG of a 14-year-old child with malformations of cortical development in the dorsolateral aspect of the right frontal lobe.

Figure 12.12

Top: Interictal EEG of a 14-year-old child with malformations of cortical development in the dorsolateral aspect of the right frontal lobe. The same EEG sample is presented in different montages. Note frequent clusters (more...)

Even when EEG is abnormal, its localisation value is often unreliable without focal ictal paroxysmal patterns at seizure onset. This is probably because of

  • – early seizure spread within and outside the frontal lobe
  • – widespread distribution of the epileptogenic brain tissue
  • – secondary bilateral synchrony and secondary epileptogenesis.

Though seizures predominate in sleep, sleep organisation is normal.

Differential Diagnosis

The typical motor seizure with or without Jacksonian march is unlikely to impose any diagnostic difficulties. However, hypermotor seizures with the bizarre movements, posturing and vocalisations are frequently misdiagnosed as pseudoseizures271 or other episodic movement disorders.240,249 Usually, normal interictal and often ictal EEG reinforces this error. Nowadays, this should be an unlikely misdiagnosis, because the constellation of hypermotor seizures is probably unique with their sudden onset and termination, stereotypical appearance in each patient and nocturnal occurrence in clusters.

Differentiation from Non-Epileptic Paroxysmal Movement Disorders

Frontal lobe hypermotor seizures should be differentiated from non-epileptic paroxysmal movement disorders,272–274 such as:

  • Psychogenic movement disorders275
  • Familial paroxysmal dystonic choreoathetosis276
  • Paroxysmal kinesigenic choreoathetosis277–279
  • Episodic ataxia type 1.273,280–283

Familial paroxysmal dystonic choreoathetosis 276 is a non-epileptic hyperkinetic movement disorder characterised by attacks of involuntary chorea, dystonia and ballism with onset in childhood. Attacks typically last from half an hour to several hours (with no signs of abnormality between attacks) and may occur several times each week. There is no impairment of consciousness and the EEG is normal during the episodes. Attacks are precipitated by a variety of factors, including caffeine, alcohol and emotion. Contrary to frontal lobe seizures, attacks in familial paroxysmal dystonic choreoathetosis can be relieved by short periods of sleep in most subjects.

Non-epileptic paroxysmal kinesigenic choreoathetosis is characterised by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements.277,278,284,285 The involuntary movements combine tonic, dystonic and choreoathetoid features on one or both sides. They are often associated with dysarthria, upward gaze and sensory aura. Consciousness is entirely intact. Their duration is usually 10–30 s and no more than 3 min. The EEG during the attacks is normal. There may be tens of attacks per day in more than 5% of patients. Onset is in the mid-teens with a range of 5–16 years. Most patients respond well to AEDs, such as carbamazepine, phenytoin or phenobarbitone.286 In nearly all patients, spontaneous remissions occur between 20 and 30 years of age.

Paroxysmal kinesigenic choreoathetosis is distinct from reflex epilepsy. However, patients may have a history of benign infantile seizures between the ages of 3 and 8 months.287 There are no differences in the clinical presentation of cases with and without infantile seizures.287 In addition, there may be a family history of epileptic seizures in 8% of cases.

Episodic ataxia type 1: Of the various types of episodic ataxias,280–283 only type 1 may impose problems in differential diagnosis. In episodic ataxia type 1, patients suffer from brief attacks of ataxia and dysarthria, lasting seconds to minutes, often associated with continuous inter-attack myokymia. Attacks are diurnal and may occur several times per day. The EEG is frequently abnormal and patients may also have seizures. Episodic ataxia type 1 is a rare, autosomal dominant, potassium channelopathy caused by at least 10 different point mutations in the KCNA1 gene on chromosome 12p13.

Differentiation from Sleep Disorders

Hypermotor seizures may be mistaken for pavor nocturnus in children or rapid-eye-movement behaviour disorder. However, the lack of dream recall, the stereotyped movements and occasional secondarily GTCS are useful distinguishing features.

So-called ‘paroxysmal nocturnal dystonia or hypnogenic paroxysmal dystonia’ is frontal lobe epilepsy.

Differentiation from Other Seizures

Temporal lobe seizures: Oro-alimentary automatisms, fear, olfactory and gustatory hallucinations, ‘absence’ with no focal symptoms, experiential phenomena and visual illusions favour temporal lobe seizures.64

Symptomatic frontal lobe absences may have similar clinical and EEG features to typical absence seizures (Figure 12.10).288–290

Management

The focal seizures of frontal lobe epilepsies are usually resistant to AEDs, but they usually protect patients against secondarily GTCS. Drug treatment is similar to that for any other type of focal seizure.

Neurosurgery has limited success.247,291 Presurgical MRI is a an important predictor of surgical outcome. Focal frontal lobe MRI lesions and pathological abnormalities correlate strongly with good outcome. In contrast, less favourable results are reported in patients with normal MRI and gliosis or no pathological abnormality on pathological examination. Multilobar MRI abnormalities have the poorest outcome.

Surface EEG and location has no predictive value in neurosurgical cases. However, generalised epileptiform discharges and generalised interictal slow activity indicates a poor neurosurgical outcome.263 The absence of generalised EEG signs is the most predictive variable for a seizure-free outcome in neurosurgery for frontal lobe epilepsy.263

Epilepsia Partialis Continua of Kozhevnikov

Epilepsia partialis continua of Kozhevnikov is rightly considered as a type of seizure/status epilepticus caused by various heterogeneous conditions in children and adults.292–299

Demographic Data

Onset occurs at any age from the very young to the very old, but probably before 16 years of age in one-third of cases. Both sexes are equally affected. Prevalence is extremely small, probably less than one per million population.295

Clinical Manifestations

The cardinal and defining symptom of epilepsia partialis continua is “spontaneous regular or irregular clonic muscle twitching of cerebral cortical origin, sometimes aggravated by action or sensory stimuli, confined to one part of the body, and continuing for a period of hours, days, or weeks”.292 Epilepsia partialis continua is a prolonged segmental myoclonic seizure lasting a few milliseconds repeated nearly every second for hours, days or months. The twitching is limited to a muscle or a small group of contiguous or unrelated muscles on one side of the body. Agonist and antagonist muscles are simultaneously contracted. Facial and hand muscles are preferentially affected.

The chronic focal epileptic muscle twitching of epilepsia partialis continua is characterised by location, frequency, intensity, duration and coexistence with other types of more conventional seizures.255,295,296,299–301 Activation, reflex, by movement or other means, is characteristic in some patients.292,294,295

Location

Epilepsia partialis continua may involve one muscle or a small muscle group of agonists and antagonists. These may be in the same region (corner of the mouth, thumb and other fingers) or occur simultaneously in other locations on the same side without direct anatomical continuity. Thus, a patient may stereotypically experience twitching of the eyelid and the shoulder or abdominal muscles simultaneously, leaving other facial or limb muscles unaffected. Facial and distal muscles of the upper limbs are more commonly affected than proximal or leg musculature. Truncal muscles on one side, such as the rectus abdominus,302 teres major295 or other muscles, may be involved.

Epilepsia partialis continua that involves both sides of the body alternately is exceptional.303

Frequency

Typically every jerk occurs about once every second or so. In one quantitative study, 33% of patients experienced 10 jerks/min, 19% 10–20 jerks/min and 14% less than 20 jerks/min.295 Epilepsia partialis continua usually persists during slow wave sleep, though is often of diminished frequency and intensity. It may be reduced or exaggerated during REM.304–307

Intensity

Commonly the jerks in epilepsia partialis continua are not violent and the patient, though distressed, can tolerate them well. Intensity varies from nearly inconspicuous to clearly visible repetitive rapid movements of the affected parts.

Duration is, by definition, for hours, days, weeks or months, though each jerk lasts for only a few milliseconds.292

Activation

That epilepsia partialis continua is sometimes ‘aggravated by action or sensory stimuli’ is a defining characteristic, though not in all patients.292 Movement or other means of activation of the affected muscles may be a characteristic feature in some patients.294

Other Type of Seizures

About 60% of patients exhibit, in addition to epilepsia partialis continua, other types of seizures, such as motor focal seizures or secondarily GTCS and, more rarely, complex focal seizures.255,295,296,299,300 These may occur independently, precede or follow the appearance of epilepsia partialis continua. More often motor focal seizures are interspersed with epilepsia partialis continua.

ILAE Classification and Definition

The ILAE Commission considers epilepsia partialis continua as “Kozhevnikov syndrome type 1” 1 and defines it as follows: “This type represents a particular form of rolandic partial epilepsy in both adults and children and is related to a variable lesion of the motor cortex. Its principal features are: (a) motor partial seizures, always well localised; (b) often late appearance of myoclonus in the same site where somatomotor seizures occur; (c) an EEG with normal background activity and a focal paroxysmal abnormality (spikes and slow waves);

(d) occurrence at any age in childhood and adulthood; (e) frequently demonstrable aetiology (tumor, vascular); and (f) no progressive evolution of the syndrome (clinical, electroencephalographic or psychological, except in relation to the evolution of the causal lesion). This condition may result from mitochondrial encephalopathy (MELAS).”1 Certain aspects of the differences between the ILAE Commission of 1985/19891 and the ILAE Task Force2 have been detailed on page 8. Rightly, the new diagnostic scheme recognised Epilepsia partialis continua of Kozhevnikov as a seizure type and not as as syndrome.2

Neurological Signs and Symptoms

Varying degrees of muscle weakness and neurological signs occur during epilepsia partialis continua.255,296,299 Permanent neurological and mental deficits may be static or progressive, and precede or follow the appearance of epilepsia partialis continua.

Patients with localised neoplastic, vascular or infectious brain lesions may have neurological deficits and isolated seizures prior to the onset of the focal status.255 In non-ketotic hyperglycaemia or drug-induced epilepsia partialis continua, the onset is sudden.294

Aetiology

There are multiple and diverse causes of epilepsia partialis continua, such as focal or multifocal brain lesions, systemic diseases affecting the brain and metabolic or other derangements (Table 12.2). Kozhevnikov-Rasmussen syndrome and malformations of cortical development are the main causes in children. Cerebrovascular disease and brain space-occupying lesions are the main causes in adults. Non-ketotic hyperglycaemia is the most common reversible cause. Other metabolic, mitochondrial or hereditary disorders are well described. Dereux (1955),308 in a thesis comprising 102 cases, found that more than 50% were caused by an ‘encephalitic process’. Rasmussen et al. (1958) described three children with epilepsia partialis continua, progressive hemiparesis, cognitive impairment and pathological changes of chronic encephalitis.

Table 12.2

Table 12.2

Causes of epilepsia partialis continua

Russian spring-summer tick-borne encephalitis is a rare cause that occurs in endemic areas. This condition is overemphasised based on the erroneous assumption309 that it caused the cases of epilepsia partialis continua described by Kozhevnikov (see review in ref 310).

Pathophysiology

The current consensus is that epilepsia partialis continua is of cortical origin and emanates mainly in the primary motor cortex. However, in all series, also utilising sophisticated neurophysiological techniques, there is a minority of patients in whom the cortical origin of epilepsia partialis continua can not be documented. For example, in the study of Cockerell et al. (1996),295 of 16 patients who underwent detailed clinical and neurophysiological assessments, only six had direct EEG and EMG evidence of a cortical origin of their jerks; five patients had indirect evidence of a cortical origin, two did not have myoclonus of cortical origin but of some other source (brainstem and basal ganglia) and the origin in the remaining three patients was uncertain.295

Diagnostic Procedures

The yield of investigative procedures is cause dependent. Around two-thirds of patients have abnormal brain MRI scans and EEG, which get worse in progressive disorders such as Kozhevnikov-Rasmussen syndrome. Ictal EEG may or may not show epileptiform abnormalities concomitant with the jerks (Figures 12.13 and 12.14). Typically, jerk-locked back-averaged cortical potentials appear in the contralateral primary motor area preceding the jerks by a few milliseconds, sensory evoked potentials are of high amplitude (Figure 12.15) and there is a rostro-caudal pattern of muscle recruitment with co-contraction of agonist and antagonist muscles. PET and SPECT scans often localise the abnormal region, but they are not specific. Screening for metabolic and mitochondrial disorders may be necessary and a few cases are of unknown origin.

Figure 12.13. Epilepsia partialis continua of 3 days’ duration, ending with hemiconvulsions.

Figure 12.13

Epilepsia partialis continua of 3 days’ duration, ending with hemiconvulsions. Sample from a video EEG of a girl aged 12 years. She has epilepsia partialis continua, which started at the age of 4 years and continues (more...)

Figure 12.14. Epilepsia partialis continua of 3 days’ duration in an elderly woman in a coma.

Figure 12.14

Epilepsia partialis continua of 3 days’ duration in an elderly woman in a coma. The right vastus medialis and right biceps brachius muscles were involved. Note that the only concurrent EEG abnormality during the jerking (more...)

Figure 12.15. Neurophysiological investigations in a man aged 26 years with onset of epilepsia partialis continua at the age of 25.

Figure 12.15

Neurophysiological investigations in a man aged 26 years with onset of epilepsia partialis continua at the age of 25. This consisted of continuous and arrhythmic twitching of various muscles of the left leg and particularly (more...)

Differential Diagnosis

Epilepsia partialis continua should not be difficult to diagnose on clinical grounds. There are not many other conditions that exhibit the characteristic segmental, continuous muscle twitching of this type. EEG may or may not be useful. A normal ictal EEG is not against this diagnosis. Brain imaging may or may not be abnormal. The main difficulty is to differentiate the genuine cortical from the non-cortical cases, and this is often a formidable task without appropriate neurophysiological examinations (jerk-locked back averaging, somatosensory evoked responses and sequential EMG). In clinical terms, the coexistence of other types of focal epileptic seizures practically identifies cortical epilepsia partialis continua.

Tremors, ticks and extrapyramidal disorders emphasised in relevant reviews or reports rarely, if ever, have this constant, unilateral and highly localised appearance of epilepsia partialis continua. However, difficulties may be imposed by ‘hemifacial spasm’, which is probably due to ipsilateral facial nerve root compression and segmental demyelination. Hemifacial spasm, like epilepsia partialis continua, manifests with unilateral painless irregular and continuous clonic twitching of the facial muscles. It affects mainly women, aged 50–60 years, without known antecedent causes other than Bell’s palsy in a few cases. The spasms usually begin in the orbicularis oculi and gradually spread to other facial muscles and the platysma of the face. Like epilepsia partialis continua, facial spasms may be induced or aggravated by voluntary and reflex movements of the face.311

Patient note

A 50-year-old woman had nearly continuous twitching in the left side of the face for 2 months. The diagnosis of hemifacial spasms was made by eminent neurologists. However, MRI and subsequent surgery revealed a large glioblastoma in the right side of the brain.

Once the diagnosis of epilepsia partialis continua is made, the underlying cause should be thoroughly sought with clinical and investigative means mandated by the causative factors listed in Table 12.2.

Prognosis

Epilepsia partialis continua is a symptom of a group of heterogeneous disorders that may be progressive, static or reversible (Table 12.2). Therefore, the long-term prognosis is cause-dependent and is usually poor. Most patients will continue with intractable epilepsia partialis continua and also develop neurological and mental defects.

Only a few patients may have a remission. Drug-induced epilepsia partialis continua disappears following the removal of the offending agent. Similarly, epilepsia partialis continua occurring in the setting of non-ketotic hyperglycaemia is reversible once the metabolic defect is corrected.

Management

Epilepsia partialis continua is resistant to treatment with AEDs. Clonazepam, valproate, carbamazepine and new broad-spectrum AEDs, such as levetiracetam and topiramate, are probably the most effective.

Successful treatment with multiple subpial transections has been reported in only a minority of operated patients.295,298

Parietal Lobe Epilepsies

Parietal lobe epilepsies manifest with seizures originating from a primary epileptic focus anywhere within the parietal lobe.1,312–324

The clinical seizure characteristics, EEG findings and results of neuroimaging studies have been established mainly in neurosurgical series of patients with a carefully documented seizure of parietal lobe origin.312–314,318,319,321–324 The report by Kim et al. (2004)324 is an excellent description of the modern approach to parietal lobe epilepsies.

Demographic Data

Parietal lobe epilepsies may start at any age. Both sexes are equally affected. Age at onset is much later in patients with tumours319 than in those without tumours.318 Parietal lobe epilepsy is relatively rare and probably accounts for 6% of all focal epilepsies in neurosurgical series.325 In one report, they were twice as common as occipital lobe seizures.315

Clinical Manifestations

Seizures emanating from the parietal lobes are mainly simple focal without impairment of consciousness. They manifest with subjective symptoms (auras), which are, in order of prevalence:

  • somatosensory
  • somatic illusions (subjective disturbances of body image)
  • vertiginous
  • visual illusions or complex formed visual hallucinations
  • receptive or conductive linguistic disturbances.

Clinical seizure manifestations are usually related to the epileptogenic location, anterior or posterior, of the dominant or non-dominant parietal lobe. Onset with sensorimotor symptoms is usually associated with anterior parietal lobe foci, whereas more complex symptomatology emanates from posterior parietal lobe regions. Approximately 50% of patients experience more than one type of seizure.324

Somatosensory Seizures

Somatosensory seizures are by far the most common type (around two-thirds of cases).319

ILAE Classification and Definitions

Parietal lobe epilepsies have not yet been detailed in the new ILAE diagnostic scheme.10 The 1989 ILAE Commission classifies parietal lobe epilepsies among the localisation-related (focal, local, partial) epilepsies and epileptic syndromes, but describes parietal seizures rather than parietal lobe syndromes:1

“Parietal lobe epilepsy syndromes are usually characterized by simple partial and secondarily generalized seizures. Most seizures arising in the parietal lobe remain as simple partial seizures, but complex partial seizures may arise out of simple partial seizures and occur with spread beyond the parietal lobe. Seizures arising from the parietal lobe have the following features: Seizures are predominantly sensory with many characteristics. Positive phenomena consist of tingling and a feeling of electricity, which may be confined or may spread in a Jacksonian manner. There may be a desire to move a body part or a sensation as if a part were being moved. Muscle tone may be lost. The parts most frequently involved are those with the largest cortical representation (e.g., the hand, arm, and face). There may be tongue sensations of crawling, stiffness, or coldness, and facial sensory phenomena may occur bilaterally. Occasionally, an intraabdominal sensation of sinking, choking, or nausea may occur, particularly in cases of inferior and lateral parietal lobe involvement. Rarely, there may be pain, which may take the form of a superficial burning dysaesthesia, or a vague, very severe, painful sensation. Parietal lobe visual phenomena may occur as hallucinations of a formed variety. Metamorphopsia with distortions, shortenings, and elongations may occur, and are more frequently observed in cases of nondominant hemisphere discharges. Negative phenomena include numbness, a feeling that a body part is absent, and a loss of awareness of a part or a half of the body, known as somatoagnosia. This is particularly the case with nondominant hemisphere involvement. Severe vertigo or disorientation in space may be indicative of inferior parietal lobe seizures. Seizures in the dominant parietal lobe result in a variety of receptive or conductive language disturbances. Some well lateralised genital sensations may occur with paracentral involvement. Some rotatory or postural motor phenomena may occur. Seizures of the paracentral lobule have a tendency to become secondarily generalized.”

Quality

Various types of paraesthetic, dysaesthetic and painful sensations are described, such as tingling, numbness, thermal, burning, tickling, pricking, creeping, tight, crawling, electric and their variations. Tingling may be the most characteristic symptom (76% in one study).326 There may be tongue sensations of crawling, stiffness or coldness. The same patient may experience different types of sensation in different seizures.

Patient note

They all start with a tingling sensation around the left side of my lip. This lasts for 10–20 s before spreading to my left arm. Then I lose coordination and power in my left arm, which may start convulsing with little if any manifestations from my leg. The whole seizure lasts for approximately 1 11/42 min. During this time, I am able to talk and understand.

Pain, sometimes excruciating, is experienced by 25% of patients with somatosensory seizures.315,318,319,322,327,328 Pain is usually unilateral, but may be cephalic or abdominal.327 When lateralised, the painful symptoms are contralateral to the side of seizure origin.327

Symptom Location

The face (mainly lips and tongue), hand (mainly thumb) and arm that have the largest cortical representation (homunculus of Penfield) are more likely to be involved. Facial sensory phenomena may occur bilaterally.329 Symptoms may be static and remain confined to their region of origin during the whole seizure (40% of cases). Somatosensory symptoms often march in a manner similar to the Jacksonian motor seizure. A bilateral or discontiguous manner of spread is rarer. Unilateral somatosensory seizures are usually contralateral to the epileptogenic zone. Seizures ipsilateral to the side of seizure origin are exceptional.313

Patient note

It is numbness or a hot feeling restricted to the corner of my left lip of the size of no more than a 2-pence piece. This lasts for 1–3 s and comes approximately once every week. On rare occasions, this numbness spreads to my left hand for a second and at the same time I am unable to articulate words. This also may be followed by ‘shaking of the lips’. On eight occasions in 14 years, this was followed by convulsions.

Ictal sensations in the genital areas and the rectum, and orgasmic seizures are infrequent, but patients may be embarrassed to report them.1,315,319,330,331 Postictal or peri-ictal true masturbation may happen.330 Sexual dyspraxic automatisms (i.e. fondling the genitals) occur only in the postictal phase of seizures.

Objective Ictal Somatosensory Deficits

Objectively demonstrable transient somatosensory deficits may be common if tested during the seizure. For example, a patient of Penfield, while undergoing electrocorticography under local anaesthesia, had an electrically induced seizure restricted to the parietal lobe.51 The patient was unaware of any specific symptoms, but two-point discrimination was impaired in the contralateral hand and returned to normal at seizure termination.

Disturbances of Body Image and Somatic Illusions

Disturbances of body image and somatic illusions are the second most common ictal symptoms of parietal lobe seizures. They include illusions of distorted posture, limb position or movement, a feeling that an extremity or a body part is alien or absent, dissociations and misperceptions of location and body part identity. Patients describe sensations of twisting, swelling, shrinking, turning or movement in one extremity or in the body, a feeling that one leg is absent and displacement of a limb or the body:

Patient note

Having my body bend toward the left, I just sort of swayed.318,319

Most patients have paraesthesia associated with these illusions. Ictal somatosensory hallucinations are rare.25,51

Ictal somatic illusions probably reflect seizure discharges in the inferior parietal lobule and superior part of the postcentral gyrus of the non-dominant hemisphere.315

Somatoagnosia (from the Greek words soma [body] and agnosia [ignorance]) is the inability to recognise the affected body part as one’s own. Somatoagnosia and most of the somatic sensations occur more frequently with dysfunction of the non-dominant cerebral hemisphere.332–334 Ictal limb agnosia (sudden loss of sensation in a limb) and phantom limb sensations (the sense that the limb is in a position that is not the true position) probably originate in the posterior parietal region.335,336 Neglect is more commonly associated with the right rather than the left inferior parietal lobe. These auras may reflect ictal impairment ‘in the body image mechanism of the posterior parietal lobe’. 335

Illusions of movement are often typical of parietal lobe seizures,337,338 while the sensation of a desire to move emanates from the precentral gyrus.339

Other Ictal Subjective Symptoms

Vertigo and other vertiginous sensations of an illusion of rotatory body movement are well reported and probably about 10% as ictal manifestations of parietal lobe seizures.315,318,319,340 They are elicited predominantly from the temporo-parietal border.17,341

Visual illusions and complex formed visual hallucinations occur in about 12% of patients with parietal lobe epilepsy. Images may be larger or smaller, close or far away, or moving though static. Ictal visual illusions, such as micropsia, metamorphopsia, autoscopia and palinopsia, most likely emanate from the non-dominant parietal regions.

Linguistic Disturbances

Dominant temporal-parietal lobe seizures are associated with a variety of linguistic disturbances, alexia with agraphia and significant calculation defects. Non-dominant parietal-occipital-temporal seizure activity usually results in significant spatial disturbances.

Inhibitory motor seizures, ictal hemiplegia 322 or negative motor manifestations, including drop attacks,318 are exceptional. An inability to move one extremity or a feeling of weakness in the hand contralateral to the epileptogenic zone may be more common than reported.319

Patient note

On most occasions my left hand becomes numb, but in a few other instances, it becomes heavy and I am unable to move it for a minute or so.

Seizure Spreading to Extraparietal Regions

Simple focal seizures often spread to extraparietal regions producing unilateral focal clonic convulsions (57% of patients), head and eye deviation (41% of patients), tonic posturing of usually one extremity (28% of patients) and automatisms (21% of patients).

Most patients also suffer from secondarily GTCS, but these are usually infrequent.324

Duration of Seizures

The duration of seizures varies from a few seconds to 1–2 min.316 Prolonged isolated sensory auras comparable to epilepsia partialis continua, but without any motor manifestations, have been reported51,318,319 and this condition may be misdiagnosed as non-epileptic psychogenic seizures.342

Postictal Manifestations

Postictal manifestations are usually short,316 though Todd’s paralysis (22%) and dysphasia (7%) may be common.318

Epileptogenic Localisation

Seizures of the primary sensory cortex typically produce contralateral positive or negative symptoms. However, focal sensorimotor phenomena at the onset also occur with seizures emanating from posterior parietal regions.325 This means that the primary epileptogenic focus is clinically silent and that symptoms are produced by spreading of the ictal discharge to the eloquent ictal symptomatogenic zone of the postcentral gyrus.51,324 Bilateral sensory symptoms usually derive from the secondary sensory area.51,342

Ictal sensations in the genital areas usually emanate from the parietal paracentral lobule.1,315,318 Ictal pain is usually reproduced by stimulating area 5a, behind the postcentral gyrus.318,319,343,344

Precipitating Factors

Seizures may be provoked by movements of the affected part of the body, tapping or other somatosensory stimuli.345,346 These are exceptional in neurosurgical series.318

Patient note

In one patient, seizures frequently occurred when she was trying to open a container or package.313,322,327

Accidental finger amputation resulted in seizure control in a boy whose seizures included ictal sensory loss in one arm provoked by using cutlery while eating.347

Sensorimotor seizures may also be triggered by music348 or toothbrushing.349

Giant EEG spikes evoked by somatosensory stimuli in benign childhood seizure susceptibility syndrome are detailed on page 255.

Aetiology

The aetiology is diverse and includes symptomatic (Figure 12.16), probably symptomatic and idiopathic causes.

Figure 12.16. Top: Coronal and axial T1-weighted MRI demonstrating parietal subcortical heterotopia (arrows).

Figure 12.16

Top: Coronal and axial T1-weighted MRI demonstrating parietal subcortical heterotopia (arrows). Bottom left: Coronal T2-weighted MRI demonstrating bilateral perisylvian polymicrogyria.

Of 82 non-tumoural patients with parietal lobe epilepsy, 43% had a history of head trauma, 16% a history of birth trauma and the cause was unknown in 20%.318 The remaining 21% had a history of encephalitis, febrile convulsions, gunshot wounds to the head, forme fruste of tuberous sclerosis, hamartoma, vascular malformations, tuberculoma, arachnoid or porencephalic cysts, microgyria and post-traumatic thrombosis of the middle cerebral artery.318 Of the tumours, astrocytomas (62%) were more common than meningiomas (14%), hemangiomas (9%), oligodendrogliomas (9%) and ependymoblastomas (3%).319 However, patients with more aggressive tumours, such as glioblastomas, are unlikely to feature in these series.

In reports with MRI, lesions were small, indolent or non-progressive and could have been found only on pathological examination.313,314 Malformations of cortical development, mild or severe, are probably the most common cause.324,326

Diagnostic Procedures

Neurological examination is usually normal in patients with non-tumoural parietal lobe epilepsy or the abnormalities are mild. Sensory deficits, such as impaired two-point discrimination or stereoagnosia (of which patients may be unaware), mild limb atrophy and inferior quadrantic visual field defects, should be sought. Patients should also be examined for disturbances of written language, aphasia, spatial orientation and right-left disorientation.325,326 Patients with tumoural parietal lobe epilepsy have similar neurological deficits, but mild contralateral weakness is common (38%), while unilateral limb atrophy is exceptional.319

Brain imaging, preferably with high resolution MRI, is mandatory for any patient with parietal lobe epilepsy and may be abnormal in around 60% of patients (Figure 12.16).319 Other brain imaging modalities, such as FDG-PET and ictal SPECT, are useful in neurosurgical evaluations.324

Electroencephalography

Interictal EEG

Surface interictal EEG may be normal, non-specific, or even misleading.313,324 In symptomatic patients, localised slow waves may be the only interictal abnormality (Figure 12.17).318,319 Epileptiform abnormalities, if they occur, may appear in areas other than the parietal regions, involving frontal, temporal or occipital electrodes.313–315,318,319,324 Of patients with intractable parietal lobe epilepsy, 16% do not have epileptiform discharges.318 In these patients, secondary bilateral synchrony may be common (32%).318 Interictal spikes, if present, should be interpreted cautiously regarding localisation.346

Figure 12.17. Interictal EEG of a 5-year-old girl with extensive right-sided porencephaly due to brain anoxia at birth.

Figure 12.17

Interictal EEG of a 5-year-old girl with extensive right-sided porencephaly due to brain anoxia at birth. Severe right sided abnormalities of spikes, sharp and slow waves are mainly focused around the parietal regions. (more...)

In one report,313 scalp EEGs correctly localised the side and region of seizure onset in only 1 of 11 patients in whom lesions had been detected with MRI. Three additional patients with congruent parietal localisation on scalp EEG had additional misleading EEG findings.

Ictal EEG

The ictal EEG may be normal in 80% of simple focal sensory seizures.326 The prevalence of scalp EEG changes in simple focal seizures with predominant sensory symptoms is only 15%, as opposed to 33% when motor symptoms are present.350

Localised parietal seizure onset is rare (11%).313,318 Ictal onset may be distant from the area of the predominant interictal spiking,329 and ictal EEG patterns are occasionally difficult to interpret,346 particularly when seizures rapidly become generalised.

Postictal EEG

Postictal EEG may have some localising value when focal slow wave attenuation of background activity or spike activation occur.351

Differential Diagnosis

Simple somatosensory seizures, alone whether brief or prolonged, are a challenging proposition. Even if reported, they are likely to be misdiagnosed as non-epileptic psychogenic fits, transient ischaemic attacks or migraine with aura, in that order. Commonly, it is only when they progress to motor symptoms or impairment of consciousness that genuine seizures are suspected and appropriate investigations are initiated.

Differentiating pure somatosensory seizures from non-epileptic psychogenic seizures or psychiatric disturbances may be extremely difficult;342 even ictal EEG changes are not seen in 80% of patients.326 Ictal pain, sensory epilepsia partialis continua, and genital and orgasmic manifestations are unlikely to be diagnosed as epileptic seizures. Sensory Jacksonian seizures may imitate migraine with sensory aura.352 In older patients, transient ischaemic attacks are the most likely diagnostic error.

Management

Drug treatment is similar to that for any other type of focal seizures and is usually effective.

In intractable cases, neurosurgery after appropriate modern presurgical evaluation is associated with a high proportion of patients achieving a seizure-free state or remarkable improvement (> 65%).318,324 MRI abnormality, concordance of different diagnostic modalities and completeness of resection of the epileptogenic zone correlates with better outcome.313,314,323,324

However, because the parietal lobe contains highly eloquent areas, resection may lead to deficits in vision, language, praxis, attention and higher cortical function, which make surgical resection problematic.324

Occipital Lobe Epilepsies*

Clinical note

Occipital seizures originate from an epileptic occipital focus that is triggered spontaneously or by external visual stimuli.315,317,328,353–358 These epilepsies may be idiopathic, symptomatic or probably symptomatic.

Demographic Data

Symptomatic occipital seizures may start at any age and at any stage after or during the course of the underlying causative disorder. Idiopathic occipital epilepsy usually starts in late childhood (see page 249). Occipital epilepsies account for around 5–10% of all epilepsies.328 In neurosurgical series, the prevalence is about 5%,355 which is comparable to the 6% seen in demographic studies.362

ILAE Classification and Definitions

The 1989 ILAE Commission classifies occipital lobe epilepsies among the localisation-related (focal, local, partial) epilepsies and epileptic syndromes, but describes occipital seizures rather than occipital lobe syndromes:1 “Occipital lobe epilepsy syndromes are usually characterized by simple partial and secondarily generalised seizures. Complex partial seizures may occur with spread beyond the occipital lobe. The frequent association of occipital lobe seizures and migraine is complicated and controversial. The clinical seizure manifestations usually, but not always, include visual manifestations. Elementary visual seizures are characterized by fleeting visual manifestations which may be either negative (scotoma, hemianopsia, amaurosis) or, more commonly, positive (sparks or flashes, phosphenes). Such sensations appear in the visual field contralateral to the discharge in the specific visual cortex, but can spread to the entire visual field. Perceptive illusions, in which the objects appear to be distorted, may occur. The following varieties can be distinguished: a change in size (macropsia or micropsia), or a change in distance, an inclination of objects in a given plane of space and distortion of objects or a sudden change of shape (metamorphopsia). Visual hallucinatory seizures are occasionally characterized by complex visual perceptions (e.g. colourful scenes of varying complexity). In some cases, the scene is distorted or made smaller, and in rarer instances, the subject sees his own image (heautoscopy). Such illusional and hallucinatory visual seizures involve epileptic discharge in the temporo-parieto-occipital junction. The initial signs may also include tonic and/or clonic contraversion of eyes and head or eyes only (oculoclonic oroculogyric deviation), palpebral jerks, and forced closure of eyelids. Sensation of ocular oscillation or of the whole body may occur. The discharge may spread to the temporal lobe, producing seizure manifestations of either lateral posterior temporal or hippocampoamygdala seizures. When the primary focus is located in the supracalcarine area, the discharge can spread forward to the suprasylvian convexity or the mesial surface, mimicking those of parietal or frontal lobe seizures. Spread to contralateral occipital lobe may be rapid. Occasionally the seizure tends to become secondarily generalized.”1 Occipital lobe epilepsies have not yet been detailed in the new ILAE diagnostic scheme.

Clinical Manifestations

Ictal clinical symptoms of occipital lobe epilepsies are subjective, objective or both. The cardinal symptoms are mainly visual and oculomotor. Visual subjective symptoms include:

  • elementary and less often complex visual hallucinations
  • blindness
  • visual illusions
  • pallinopsia
  • sensory hallucinations of ocular movements.

Ocular subjective symptoms comprise:

  • ocular pain.

Ictal objective oculomotor symptoms are:

  • tonic deviation of the eyes (pursuit-like rather than oculotonic)
  • oculoclonic movements or nystagmus
  • repetitive eyelid closures or eyelid fluttering.

Some of these ictal manifestations, such as elementary visual hallucinations, are generated in the primary visual cortex; others, such as visual illusions, emanate from the neighbourhood of the occipital-parietal and occipito-temporal regions. Seizures may spread from the occipital to other more anterior regions of the brain generating symptoms from the temporal, parietal and frontal lobes and secondarily hemi- or generalised convulsions. Ictal or postictal headache is frequently associated with occipital seizures.

Elementary Visual Hallucinations

Elementary visual hallucinations are the most common, characteristic and well-defined ictal symptoms of occipital lobe seizures (Figure 12.18). They are usually the first, and often the only, ictal symptom during a seizure and may progress to other occipital and extra-occipital manifestations and convulsions.

Figure 12.18. Visual seizures as perceived and drawn by a patient with an interesting form of symptomatic occipital epilepsy (case detailed in ref ).

Figure 12.18

Visual seizures as perceived and drawn by a patient with an interesting form of symptomatic occipital epilepsy (case detailed in ref ). From Panayiotopoulos (1999) with the permission of the Editor of Epileptic Disorders. (more...)

Important note

Elementary visual hallucinations of visual seizures are mainly coloured and circular, develop rapidly within seconds and are brief in duration (Figure 12.18). They often appear in the periphery of a temporal visual hemifield, becoming larger and multiplying in the course of the seizure, and frequently moving horizontally towards the other side. They are fundamentally different to the visual aura of migraine for which they are often mistaken.357,363,364

Panayiotopoulos has studied the elementary visual hallucinations of idiopathic and symptomatic occipital seizures in a qualitative and quantitative chronological manner,357,364 differentiated them from the visual aura of migraine365,366 and reviewed them exhaustively from ancient times.359 The main conclusions of these studies are briefly described here.

Ictal elementary visual hallucinations (Figure 12.18) are defined by colour, shape, size, location, movement, speed of appearance and duration, frequency and associated symptoms of progression.

Colour, Shape and Size

The predominant patterns are coloured, usually multicoloured, and circular. Bright red, yellow, blue and green prevail. Shapes are mainly circular, spots, circles and balls. Individual elements are multiple and rarely single. Their size varies from ‘spots’ to rarely the size of a ‘small ball’. Coloured, square, triangular and rectangular or star-like shapes, alone or in combination with circular patterns are less frequent. Flashing or flickering achromatic lights, shades or non-circular patterns are rare. The components of visual hallucinations increase in number, size or both with progression of the seizure, particularly prior to other non-visual symptoms.

Patient note

Multicoloured blue, yellow and red, circular flickering patterns closely packed together and multiplying in the left lateral hemifield. Then it seems that the environment moves slowly and stepwise from left to right.

A ‘rainbow’ of all colours with dust blocks of shadow-like bricks in the periphery of the right eye.

Location

Their location at onset is usually unilateral, mainly in the temporal visual hemifield (Figure 12.18). They may appear in a normal, blind or damaged hemifield.367 Central or undefined localisation occurs in 10–30% of patients.

Movement

The components of elementary visual hallucinations usually multiply and become larger without any particular movement other than changing positions and luminance within their visual territory (Figure 12.18). Flickering or flashing is common. Movement towards the centre of vision or the other side is less common. Rarely, the movement is spinning, circling, rotatory, random, approaching or moving away from the patient.51,367,368

Patient note

“Visual movement was more frequently present than absent. The image might remain still, but more often it moved slowly in a certain direction or it danced, flickered, or whirled.”369

“There are 3–4 concentric spherical rings of red and yellow moving from the left to the right of my vision, and repeating the same course again and again after their disappearance on the right”. 328

Lateralisation

The side of unilateral elementary visual hallucinations is contralateral to the epileptogenic focus (Figure 12.18). Conversely, this is ipsilateral to the epileptogenic focus for unilateral visual hallucinations moving horizontally towards the other side.368,370

Vision

Ictally, vision may be obscured only in the area occupied by the visual hallucinations. However, some patients may be even able to read through them. Blurring of vision at onset, with or without visual hallucinations, may be a common mild form of visual seizure if investigated.

Patient note

The additional notable symptom that I suffer is clusters of momentary left visual field disturbances “like a momentary flickering or blurring of vision (always in the left temporal field only)”. Several of these moments can occur within, for example, a 10 min period and then several again over a similar period 1 or more hours later.

My sight deteriorates very slightly before the visual aura, but flashing does not start. It is a reduction of visual awareness of around 10%.

Duration

Visual seizures develop rapidly within seconds and they are usually brief, lasting from a few seconds to 1–3 min, rarely longer.357,364,365 Exceptionally, they last for 20–150 minutes, sometimes constituting focal visual status epilepticus without other ictal symptoms.16,359,371,372

As a rule, elementary visual hallucinations are longer prior to secondarily generalisation.

Frequency and Circadian Distribution

Visual seizures occur, often in multiple clusters, daily or weekly. Commonly, several may occur per day. They are usually diurnal, but some patients often wake up with elementary visual hallucinations.

Patient note

I would wake up from sleep either with elementary visual hallucinations or with white blindness (all white), before a generalised convulsion.

Stereotypic Appearance

Ictal symptoms of elementary visual hallucinations are stereotyped, particularly at onset, in all aspects other than duration. Exceptionally, the same patient may experience different types of seizures.

Progression to Other Occipital or Non-Occipital Seizure Manifestations

Elementary visual hallucinations may be the only seizure manifestation, but they often progress to other ictal symptoms, such as complex visual hallucinations, oculoclonic seizures, tonic deviation of the eyes, eyelid fluttering or repetitive eye closures, impairment of consciousness, experiential phenomena, hemi-anaesthesia, and unilateral or generalised convulsions. On other occasions, they progress to extra-occipital seizure manifestations by spread to the temporal, frontal or parietal regions.

Patient note

Bright, multicoloured, blue, red, yellow and green spots of light in the periphery of the right eye multiply rapidly and occupy the whole right visual field, though I can see through them. They cause me a pleasant feeling ‘because of the colours’. These are sometimes followed by distortion of the surrounding objects and persons as if ‘through the mirrors of a theme park’.

A spinning ball filled with mainly red and yellow colours on the right. This could be followed by visions of distorted bodies.

Complex Visual Hallucinations, Visual Illusions and Other Symptoms from More Anterior Ictal Spreading

Complex visual hallucinations, visual illusions and other symptoms from more anterior ictal spreading mainly occur in progression of the seizure that may terminate with hemiconvulsions or generalised convulsions. They may be the first ictal symptom, but more often follow elementary visual hallucinations.

Complex visual hallucinations may take the form of persons, animals, objects, figures or scenes. They may be familiar or unfamiliar, friendly or frightening, and simple or grotesque. They may appear in a small or large area of a hemifield, or in the centre and the whole of the visual field. They may be static, move horizontally, expand or shrink, approach or move away. In patients with visual field defects due to structural brain lesions, complex visual hallucinations appear in the defective visual field. Complex visual hallucinations of occipital seizures do not have the emotional and complicated character of temporal lobe seizures.357,364,381

Patient note

Sudden awareness of rapidly oscillating, vague, dark, disproportionate, face-like, frightening figures moving forwards and backwards in the temporal field of my left eye.

An interesting, but extremely rare ictal complex visual hallucination is autoscopia (or heautoscopy), which means viewing his own image/viewing himself.382,383 This mirror self image looks ‘real’ and is usually undistorted, silent, brief or recurrent, from the present time or from the past, framed or performing complex tasks.

Complex visual hallucinations including ictal autoscopia probably originate from occipito-parietal and occipito-temporal junction areas.

Visual illusions are misinterpretations, false percepts, of real external images. These distorted images (metamorphopsia) involve changes in size, dimension, shape, proportions, position, colour, illumination and movement, alone or in combination. Changes in perception of object size are common, the percepts being smaller (micropsia) or larger (macropsia) than the real image. Objects may be distorted in shape, pulled, compressed or rotated in lateral or vertical directions. They may appear in black and white (achromatopsia), in one colour (monochromopsia), hazy and dark or highly illuminated and bright. Motion and speed may be affected with or without distortion of direction (horizontal, vertical or rotated, approaching or moving away). Movement is faster or slower. Moving objects may appear stationary and vice versa.

Visual illusions also entail changes in spatial interpretation affecting stereoscopic vision.

Patient note

“Far objects appear near, near ones far, and convex ones concave, or vice versa.”384

Ictal visual illusions may occupy part or the whole visual field, and are probably more likely to be associated with symptomatic than with idiopathic occipital seizures.

Palinopsia

Palinopsia, that is persistence or recurrence of visual images after the exciting stimulus has been removed, is an interesting form of visual illusion associated with right posterior parieto-temporal lesions.

Patient note

He looked at a small video display unit and, after he looked away, the image of the screen persisted in the right upper corner of his vision and nearly simultaneously, started flashing at a rate of 3–5 Hz for 2 s. This was followed by visual illusions of the walls and the passengers closing in on him, ending within 5 s with GTCS.

Sensory Hallucinations of Ocular Movements

Sensory hallucinations of ocular movements, that is a sensation of ocular movement in the absence of detectable motion, is rare.

Patient note

“This involuntary movement of the eyes to the left and at a slight tilt upwards causes the pain described above. The motion to the left seems out of your control. It can be resisted but this adds to nausea and general pain.” Neither he nor the witnesses could confirm any such movement of the eyes.

Ictal Blindness (Ictal Amaurosis)

Ictal blindness (ictal amaurosis) may follow the visual hallucinations and progress to other epileptic symptoms, but often occurs as a starting or the only ictal seizure manifestation with abrupt onset.357,359,364,366,385

Patient note

I usually have millions of small, very bright, mainly blue and green coloured, circular spots of light, which appear on the left side and sometimes move to the right, but on one occasion suddenly everything went black, I could not see and I had to ask other swimmers to show me the direction to the beach.328,386

The duration of ictal blindness is usually longer (3–5 minutes) than ictal visual hallucinations; occasionally, blindness may last for hours or days (status epilepticus amauroticus).387–389 Ictal blindness and less frequently ictal hemianopia occur in one-third of patients with symptomatic and two-thirds of patients with idiopathic occipital epilepsy.

Terminology

Autoscopia (or heautoscopy) means viewing his/her own image, viewing himself.374,375

Fortification spectra in migraine are visual hallucinations with similarities to the bastioned, star-patterned, pentagonal fortifications and not of the castellated appearances of battlements.376,377 A bastion is a projecting part of a fortification, consisting of an earthwork in the form of an irregular pentagon, having its base in the main line or at an angle of the fortification. Spectrum is used by Gowers378 “to mean apparition and not a coloured band of light.”

Pallinopsia (visual persevereness) is the persistence or recurrence of visual images after the exciting stimulus has been removed. Percept is the mental image or product of perception of any object in space.

Phosphenes are subjective sensations of light due to non-luminous stimulation of the retina. Phosphenes are also used to denote visual percepts from stimulation of the visual cortex with an electrical stimulus, in which case they are usually coloured spots or circles.379

Photopsias (phos = light, opsis = appearance) are unformed flashes of light and sparks.

Scintillating (scintilla = spark) scotoma (skotos = darkness) is also used because of the sparking appearance of the visual hallucinations of migraine (brilliant flashes of light in the periphery of dark areas in the visual fields).

Teichopsia (teichos = town wall, opsis = appearance) was coined by Airy380 “to represent the bastioned form of transient hemiopsia which I have been describing, not without a reminiscence of some words of Tennyson’s:

as yonder walls

Rose slowly to a music slowly breathed,

A cloud that gathered shape.”

Visual hallucinations are subjectively experienced images in the absence of an actual external stimulus:

Elementary visual hallucinations consist of simple, usually geometric forms, spots or lines.

Complex visual hallucinations consist of objects, faces or scenes.

Visual illusions are misinterpreted false percepts of real images.

An interesting rare variation of ictal blindness is ‘white ictal blindness’.357,359 The patient can not see because everything is white.

Patient note

I can not see, like a white sheet in front of my eyes.

It is all white.

Blurring of vision as an initial seizure manifestation prior to visual hallucinations may be common if investigated.357,364,381

Patient note

It starts with a momentary flickering or blurring of vision (always in the left temporal field only) (case 7.2 in ref 328).

My sight deteriorates very slightly as it does before the aura, but flashing does not start. It is a reduction of visual awareness of around 10% (case 30 in ref 328).

Tonic Deviation of the Eyes, Oculoclonic Seizures and Epileptic Nystagmus

Tonic deviation of the eyes often, but not necessarily, followed by ipsilateral turning of the head is the most common (40–50% of cases) non-visual symptom of occipital seizures. This is similar to a voluntary, pursuit-like turning of the eyes to one side. This usually follows visual symptoms and mainly elementary visual hallucinations, but it may also occur from seizure onset. Consciousness is often, but not invariably, impaired when eye deviation occurs.

The epileptogenic focus is more likely to be contralateral to the movement of the head and the eyes if consciousness is not impaired.

Ictal nystagmus (epileptic nystagmus) is mainly horizontal and rarely vertical. The quick phase of the nystagmus is opposite to the epileptic focus, in the same direction of eye and head deviation, which may coexist, precede or follow.

Repetitive Eyelid Closures, Eyelid Fluttering and Eyelid Blinking

Repetitive eyelid closures, eyelid fluttering and eyelid blinking is an interesting ictal clinical symptom of symptomatic and idiopathic occipital epilepsy. It usually occurs after the phase of visual hallucinations, at a stage when consciousness is impaired and heralds the impending secondarily generalised convulsions. However, it may also occur alone, be inconspicuous in appearance and not be suspected as a seizure event, documented only by video EEG recordings in occipital photosensitive patients.

Eyelid opening, or ‘eyes widely opened’, is another well-described symptom in occipital epilepsy, but may also be a symptom associated with other cerebral locations. Widened palpebral fissures with fixed staring and dilated pupils are among the typical symptoms of mesial temporal lobe seizures.390

Consciousness

Consciousness is not impaired during the elementary and complex visual hallucinations, blindness and other subjective occipital seizure symptoms, but may be disturbed or lost in the course of the seizure, usually at the time of eye deviation or eye closure, and generally prior to convulsions.

Ictal or Postictal Headache

Ictal or postictal headache is frequently associated with occipital seizures. 357,359,364,366 Ictal pain is mainly orbital. It is described as a sharp, stabbing, retro-orbital pain, a sensation of bifrontal pressure, a vague ache in the head or a sensation of electricity.

Patient note

The visual hallucinations consist of vivid, flashing multicoloured lights and circular patterns that occupy and obscure my vision. Severe unilateral throbbing headache follows 1–2 min later, lasts for hours and it is often associated with vomiting (case 7.1 in ref 328).

Important note

Postictal headache, often indistinguishable from migraine, is far more common in occipital (occurring in more than 50% of cases) than in any other focal epilepsy,391,392 and may occur even after brief visual seizures.357,364 Also, postictal headache often occurs 3–15 min from the end of the visual seizure, a situation known in migraine as the ‘asymptomatic interval’ between the end of migraine aura and the onset of headache.393

Postictal hemianopia may occur.

Patient note

When the visual hallucinations ceased completely, I had almost no vision in the left eye, only blackness (case 7.2 in ref 328).

Seizure Spreading

Seizures may spread from the occipital to other more anterior regions of the brain, generating symptoms from the temporal, parietal and frontal lobes and secondarily hemi- or generalised convulsions. Infra-calcarine occipital foci will propagate to the temporal lobe causing complex focal seizures, while supra-calcarine foci tend to propagate to the parietal and frontal areas giving rise to predominantly motor seizures.

Important note

Progression to temporal lobe seizure symptomatology is rather exceptional in idiopathic cases.

Aetiology

Aetiology may be idiopathic, structural or metabolic.357,359,364,366

In symptomatic occipital epilepsy, lesions may be congenital, residual or progressive resulting from vascular, neoplastic, metabolic, hereditary, congenital, inflammatory, parasitic, systemic diseases and infections. Malformations of cortical development are a common cause, which is being increasingly recognised with MRI, as it is the case today in all focal symptomatic or probably symptomatic epilepsies (Figure 12.8).355

Metabolic or other derangements, such as eclampsia, may have a particular predilection for the occipital lobes and cause either occipital ‘seizures that do not require a diagnosis of epilepsy’ or permanent occipital lesions leading to symptomatic occipital epilepsy.394 There is an interesting association between coeliac disease (CD) and occipital lobe epilepsy.395 Occipital seizures may be the first manifestation of a devastating course, as in Lafora disease for example,396–398 or mitochondrial disorders.399

Coeliac Disease and Occipital Epilepsy

The association between occipital seizures and CD, with or without bilateral occipital calcifications, has been well documented, mainly by Italian authors. The book ‘Epilepsy and other neurological disorders in celiac disease’400 is highly recommended.

Diverse epileptic conditions with onset in childhood and early adolescence have been reported in patients with symptomatic or asymptomatic CD. These conditions include severe epilepsies, such as Lennox-Gastaut syndrome, and myoclonic epilepsies with ataxia, but more commonly symptomatic occipital epilepsy.

Age at onset of epilepsy is 1–28 years, and most commonly between 4 and 13 years. Occipital seizures are by far the commonest, though other focal fits, GTCS and absences may occur from the onset of epilepsy. In most patients, seizures start before the detection of CD and the institution of a gluten-free diet (GFD). GFD seems to control the seizures if started soon after the onset of epilepsy and early in childhood. However, seizures may also start after GFD, in which case they are more likely to be symptomatic, drug-resistant occipital epilepsy manifesting mainly with elementary visual hallucinations. A few cases may have a benign course, but the majority progress to other seizure types and an epileptic encephalopathy with delayed mental development, despite an initial relatively good response to treatment. The severity of the epileptic seizures is not proportional to the severity of the cerebral calcifications.

EEG abnormalities initially consist mainly of occipital paroxysms, occipital spikes or generalised discharges. Activation of occipital spikes by intermittent photic stimulation (IPS) is not uncommon. Multispike discharges in the sleep EEG often betray their symptomatic character.

Important note

A history of gastrointestinal symptoms, nutritional problems, a positive family history of CD and an atypical Sturge-Weber syndrome without a cutaneous naevus should raise the possibility of this syndrome. Occipital seizures in Sturge-Weber syndrome are rare.

Eclampsia and Occipital Seizures

There is a selective vulnerability of the occipital lobes to eclamptic hypertensive encephalopathy. Neurological symptoms of eclampsia include seizures, headache, blindness and impairment of consciousness. Seizures may be GTCS or focal visual seizures with secondarily GTCS. Seizures persisting after recovery from eclampsia are rare.394 Recent reports indicate that eclampsia may also be a risk factor for MTLE-HS.401

Lafora Disease and Occipital Seizures

Lafora disease is an autosomal recessive disorder among the progressive myoclonic epilepsies, characterised by the presence of Lafora bodies (periodic acid–Schiff-positive diastase-resistant polyglucosan inclusions) found in the brain, skin, liver and other body tissues.402 The disease is caused by mutations in the EPM2A gene on chromosome 6q24. Onset of the disease is around the age of 14 years (common range 8–18 years), mainly with occipital seizures, myoclonic jerks and GTCS. Occipital seizures occur in 30–50% of patients, may be spontaneous or photically induced, and consist of complex and elementary visual hallucinations. In the initial stages, Lafora disease may imitate idiopathic generalised epilepsies, with myoclonic jerks, GTCS and generalised discharges of polyspikes and slow waves that are spontaneous or photically induced, and a relatively normal EEG background. Occipital involvement is indicated by occipital polyspikes and visual seizures, but these rarely occur without coexisting myoclonic seizures, GTCS and EEG generalised discharges that are also often induced by IPS. Background EEG may be abnormal before onset of seizures, but may also be normal in the initial stages of the disease. Cognitive decline is relentless either before or soon, within months, after the onset of seizures, and death is unavoidable within 1–10 years.

Lafora disease should be suspected when the onset of occipital seizures is combined or followed by myoclonus and progressive mental decline.

Pathophysiology

Elementary visual hallucinations are generated from the primary visual cortex, complex visual hallucinations from the occipito-parietal-temporal junction areas, and visual illusions from the non-dominant parietal regions.328

Ictal blindness is probably due to contralateral seizure spread to involve both occipital lobes or to inhibition of the visual cortex by the seizure discharge.403

Because of the frequent occurrence of postictal headache in occipital epilepsy, it is reasonable to suggest that occipital seizures often generate migraine-like attacks and that the occipital lobes are preferentially associated with the trigeminovascular or brainstem mechanisms responsible for migraine headache.404 Postictal headache of occipital seizures may be related to serotonergic mechanisms and respond to oral sumatriptan.405 Another similarity with migraine is that postictal headache often occurs 3–15 minutes from the end of the visual seizure, a situation described in migraine as the ‘asymptomatic interval’ between the end of migraine aura and the onset of headache.393

Thus, the ‘occipital seizure-migraine’ sequence357,364,366,406 appears to be much more common than the previously prevailing view of ‘migraine visual aura triggering epileptic seizures’ or ‘migraine-epilepsy syndromes’.407–409

Diagnostic Procedures

The discovery of the underlying cause in symptomatic occipital epilepsies may require haematology and biochemistry screening for metabolic disorders, molecular DNA analysis, or even skin or other tissue biopsy.328 High resolution MRI is necessary in all patients with occipital lobe epilepsy (Figure 12.19).328 Unsuspected residual or progressive lesions, tumours, vascular malformations and malformations of cortical development are all detected by MRI. CT scanning is far inferior to MRI and insensitive to focal cortical dysplasia. Conversely, the calcifications of CD may be missed with MRI, but this is rare. Functional brain imaging for localisation is of practical value in neurosurgical cases.410

Figure 12.19. Patient with visual seizures and focal status epilepticus of occipital lobe epilepsy.

Figure 12.19

Patient with visual seizures and focal status epilepticus of occipital lobe epilepsy. Three dimensional reconstruction of the brain demonstrating abnormal gyral patterns on the right. A. Surface rendering of cortex viewed (more...)

Electroencephalography

EEG is essential, but certain limitations should be recognised.

Interictal EEG

In symptomatic cases, the background EEG is usually abnormal with posterior lateralised slow waves. Unilateral occipital spikes or fast multiple spikes and, occasionally, occipital paroxysms occur. There may be occipital photosensitivity.328 Worsening of the background EEG is significant in the diagnosis of progressive causes.

In idiopathic cases, such as Gastaut-type idiopathic childhood occipital epilepsy and photosensitive occipital epilepsy, the background interictal EEG is normal.328 Occipital spikes and occipital paroxysms, spontaneous, evoked or both, are often abundant. They disappear with age frequently long after cessation of the occipital seizures.

Ictal EEG

Surface ictal EEG in occipital seizures, irrespective of cause, usually manifests with paroxysmal fast activity, fast spiking or both, localised in the occipital regions with occasional gradual anterior spreading and generalisation with irregular spike wave discharges or monomorphic spike and wave activity. Brief occipital flattening may be seen before the fast rhythmic pattern. Often, in patients with symptomatic occipital lobe epilepsy, the ictal discharge is more widespread (regional) rather than of a precise occipital localisation. Usually, there is no postictal localised slow activity unless the seizure is prolonged or progresses to secondarily GTCS.

Important note

In one-third of patients (30%), the ictal surface EEG does not show any appreciable changes in occipital seizures.328

Differential Diagnosis

Occipital seizures should not be difficult to diagnose, but should be first differentiated from migraine, normal phenomena and psychogenic or other causes unrelated to seizures.328

Differentiating Visual Seizures from Migraine

Visual Aura of Migraine
Patient note

“I was startled by a single, shadowy appearance at the outside corner of the field of vision of the left eye. It gradually advanced into the field of view and then appeared to be a pattern of straight-lined angular forms, very much in general aspects like the drawing of a fortification, with salient and re-entering angles, bastions and ravelins with some suspicion of faint lines of colour between the dark lines.” Sir JFW Herschel (1866)376

Visual Seizure
Patient note

“They commenced with the appearance of several small spheres, white in the centre with an intermediate zone of blue and outside this a ring of red, immediately to the left of the point at which the patient gazed; from here they moved either at a uniform rate or in jerks to the left and downwards…In all attacks the eyes deviated towards the left and the head turned in the same direction as soon as the visual spectra appeared.” G Holmes (1927)16

Misdiagnosis of visual seizures as migraine appears to be high though their differentiation should not be difficult.328,357,364 Occipital seizures manifesting with elementary visual hallucinations, blindness and headache, alone or in combination, may imitate migraine, which is the reason that they are often mistaken as migraine with aura, acephalgic or basilar migraine (Table 12.3).328,357,364 Even lesional occipital epilepsy is often misdiagnosed as migraine and, on many occasions, visual seizures are considered as visual aura of migraine, thus limiting their prognostic significance regarding continuation of treatment.357 The following are quotes from medical referrals of patients with visual seizures:

Table 12.3. Differential diagnosis of occipital seizures from basilar migraine or migraine with aura.

Table 12.3

Differential diagnosis of occipital seizures from basilar migraine or migraine with aura.

Patient note

“This patient has visual migraine-like disturbances, such as teichopsias.”

“Scintillating scotoma or sparkling scotoma of migraine.”

“Migrainous aura before the fit.”

There are two main reasons that visual seizures are misdiagnosed as migraine.357,359,364,366 Firstly, visual seizures are not examined in a comprehensive manner; instead they are abbreviated to terms such as ‘scintillating scotoma’ or ‘teichopsia’, which often do not represent the actual description of the patients. Secondly, their differential diagnostic criteria have only recently been adequately studied and addressed by Panayiotopoulos.357,363,364 The diagnosis of visual seizures may comfortably rely on clinical criteria only; other investigative procedures are essential, but even ictal EEG may not identify one-third or more of cases.

Important note

Factors contributing to error in the diagnosis of visual seizures
The major contributory factor to error is that the description of visual hallucinations is often abbreviated in terms such as fortification spectrum, teichopsia, scintillating scotoma, phosphenes and their variations.363 Their meaning does not always represent the actual descriptions, which should be meticulously requested. Erroneously, they are frequently unquestionably equated with migraine.

The quality and the chronological sequence of ictal elementary visual hallucinations are markedly different from the visual aura of migraine. Visual seizures and the visual aura of migraine may imitate each other, but their true identity can not easily escape clinical scrutiny.

Though brief duration is significant, there are many more clinical manifestations to differentiate visual seizures from the visual aura of migraine (Table 12.3).

Clinical note

Diagnostic clues
As a rule, brief (< 1 min), elementary visual hallucinations that develop rapidly within seconds, with coloured and circular patterns and daily frequency are probably pathognomonic of visual seizures, despite severe headache and vomiting that may follow. EEG may be normal, show non-specific abnormalities or reveal slow focal or occipital spikes. A high resolution MRI is mandatory as it may detect a structural lesion requiring early attention and management.

The visual aura of migraine with aura and acephalgic migraine are adequately studied and illustrated in all relevant textbooks and publications. In one of the most detailed, a nosographic analysis411 describes migraine visual aura as:

Patient note

“started as a flickering, uncoloured, zigzag line in the centre of the visual field and affected the central vision. It gradually progressed over > 4 min, usually lasting < 30 min, towards the periphery of one hemifield and often left a scotoma. The total duration of visual auras was 60 min. Only four patients had exclusively acute onset visual aura.” 411

Furthermore, migraine visual aura:

  • rarely has daily frequency
  • non-visual ictal occipital symptoms, such as eye and head deviation, and repetitive eyelid repetitive do not occur
  • it is debatable and probably exceptional to progress to non-visual epileptic seizures.

Less typical features of migraine visual aura, such as spots, circles and beads, with or without colours, may be experienced during the migraine visual aura, but usually they are not dominant. More importantly, clustering of other symptoms, as above, betrays their migraine nature.

Clarifications on Migraine and Epilepsy

Migraine and epilepsy are the commonest neurological disorders. The prevalence of migraine is probably around 6% in men and three times more common in women. The prevalence of epilepsy is around 0.5%, and men and women are equally affected. If there was a relation between them, this would be obvious in our everyday neurological practice. It would not be revealed only through obscure and complicated cases with bizarre symptomatology. It would be simple and common. It is not. The problem is that occipital seizures are not appropriately differentiated from migraine and, therefore, they are often erroneously diagnosed as migraine.

Seizures may be triggered from a migrainous event or caused by a migraine-stroke, but this is rare. There should be no doubt that a cerebral infarct due to severe migraine can be responsible for symptomatic seizures. Also, there should be no reason that epileptic seizures, so vulnerable to extrinsic and intrinsic precipitating factors, could not also be susceptible to cortical changes introduced by migraine. Thus a migrainous attack may also be able to trigger epileptic seizures in susceptible individuals. However, both these cases are rare. In my opinion, the commonest reason for their association is the coincidence of two of the more common neurological disorders, and an erroneous interpretation of epileptic seizures as migraine, and less often vice versa. The emerging and more realistic concept of occipital seizures triggering migrainous headache needs consideration and exploration. More importantly, patients with daily visual seizures that may progress to convulsions merit a precise diagnosis and appropriate treatment, probably with carbamazepine. Most of these patients with visual seizures are misdiagnosed as migraine with aura, basilar migraine, acephalgic migraine or migralepsy, simply because physicians are not properly informed about the differential diagnostic criteria. As a result, diagnosis, appropriate investigations and treatment may be delayed for years. There are numerous published reports of such misdiagnosis.

Based on the results of my studies, my thesis is that the visual aura of migraine is entirely different from that of visual seizures when all their components are synthesised together (Table 12.3).

Basilar migraine of Bickerstaff 412,413 is characterised by transient and fully reversible symptoms of aura, indicating focal dysfunction of the brainstem, the occipital lobes or both, followed by headache.361 Common neurological symptoms of aura include visual manifestations, dizziness, vertigo and tinnitus, ataxia, bilateral weakness and dysaesthesia, diplopia, dysarthria and decreased hearing. Visual symptoms mainly consist of dimming of vision, blindness, tunnel vision, hemianopia and scotomata. Elementary visual hallucinations are usually bilateral, described as ‘teichopsia’, ‘flashes or blobs of light’, ‘coloured figures’ or ‘dysmorphopsia’. Aura symptoms develop gradually over 4 min and last for less than 30 min to 1 hour. Impairment or loss of consciousness without convulsions may occur in one-quarter of patients between the aura and the headache phase.

Patient note

“The loss of consciousness is described as curiously slow in onset – never abrupt, and never causing the patient to fall or to be injured. A dreamlike state sometimes precedes impairment of consciousness. The degree of impairment of consciousness was never profound but the patients were never unrousable; on vigorous stimulation they could be aroused to cooperate but they returned to unconsciousness when the stimulation ceased.”413

Attacks of basilar migraine are usually infrequent and, over the years, they may cease or be replaced by common migraine with or without aura.361

Migralepsy versus Epilepsy-Migraine

Migralepsy, migra(ine) and (epi)lepsy, is a term used to denote “a seizure that may be a composite of symptoms encountered in epilepsy and migraine”.18,414 The term intercalated seizures is used to denote epileptic seizures occurring between the migrainous aura and the headache phase of migraine.415 There should be no reason that epileptic seizures, which are so vulnerable to precipitating factors, could not be susceptible to cortical changes induced by migraine. However, this is exceptional considering that migraine and epilepsy are the most common brain diseases. According to a recent review, most of the reported cases are likely to be genuine occipital seizures imitating migraine aura.357,364 Of the most influential cases that I have detailed,357,364 two of three ‘migralepsy’ patients,18 one case of ‘basilar migraine and epilepsy’ 416 and one boy with ‘juvenile migraine with epilepsy’, 417 all had symptoms of visual seizures as defined in this book, which were interpreted as migraine aura. The patient of Barlow417 with symptomatic occipital epilepsy may be indicative.

Patient note

This boy at age 13 years, “While ski-ing he saw blue to the right associated with blurred vision that lasted for a few seconds”, after which he vomited, became confused for 30 minutes, followed by severe throbbing headache. Subsequently he had occasional “episodes of similar visual disturbance” diagnosed as juvenile migraine and successfully treated with phenytoin. An arteriovenous malformation was found in the left occipital lobe. “Visual scotomata accompanied by flashing lights that only occasionally were followed by headache” continued postoperatively.

None of 1550 patients I have studied had any evidence of seizures developing from migraine aura, though this was often the initial erroneous diagnosis on referral.357 Conversely, postictal headache and other migraine-like symptoms frequently occurred after occipital seizures. However, an incontrovertible diagnosis may be difficult in some equivocal cases.

Patient note

A 38-year-old man who, while working with the computer, saw flashing lights in between his eyes. They were moving for a few centimetres upwards and to the right repetitively. Gradually the intensity of the light and the area increased over the next 30 min obscuring his vision. This ended with a GTCS as he was entering the examination room of his general practitioner, which he had walked to for help. He had never had similar symptoms, seizures or migraine in the past. MRI was normal. EEG showed minor non-specific abnormalities.

Important note

The concept of migralepsy and its synonymous intercalated seizures or of a migraine-epilepsy sequence needs re-evaluation based on accurate diagnosis. In most instances, it is seizures imitating migraine or an epilepsy-migraine sequence.

Patient note

Misconceptions

There is a misconception that there is a syndrome of ‘basilar migraine with EEG occipital paroxysms’, which is perpetuated in every relevant publication and textbook to date. Retrospective analysis of cases described as “basilar migraine with occipital paroxysms” 386,418,419 showed that these patients genuinely suffer from idiopathic occipital epilepsy.328,420

Differentiating Ictal Deviation of the Eyes of Occipital versus Extra-Occipital Origin

I am not aware of any study that has compared ictal deviation of the eyes, head or both of occipital origin with that of extra-occipital origin. The following conclusions are derived from my personal experience, supplemented by relevant reports in the literature.

In occipital epilepsy, the deviation of the eyes is usually pursuit-like or tonic, rarely clonic and different to the oculoclonic ictal symptoms that are often seen in focal motor seizures of extra-occipital, mainly frontal origin. Occipital oculotonic seizures are similar to a voluntary, pursuit-like turning of the eyes to one side that, by itself, could not be considered as an abnormal movement by witnesses. They usually follow visual symptoms and mainly elementary visual hallucinations, but may also occur ab initio. At this stage, consciousness is often but not invariably impaired. This phase may progress to unilateral clonic seizures of the face and the extremities, with or without progressing to GTCS.

Conversely, ictal eye movements of extra-occipital origin are more violent and look unnatural. Ipsilateral eyelid tonic or clonic convulsions are commonly associated with upward deviation of the eyeballs. It is simultaneous, and precedes or follows tonic or clonic convulsions of other facial, neck and shoulder muscles of the same side (e.g. as in hemifacial Rolandic seizures).

Differentiating Idiopathic from Symptomatic Occipital Epilepsy

Differentiation between symptomatic and idiopathic occipital epilepsy is essential with regard to prognosis and management.

The visual seizures of symptomatic versus idiopathic occipital epilepsy are indistinguishable.357 The only difference is that symptomatic visual seizures more frequently progress to other extra-occipital seizure manifestations and mainly temporal lobe seizures. Though progression to ictal motor manifestations may be common in both, temporal lobe symptoms are nearly exclusively seen in symptomatic occipital epilepsy. A normal neurological state (including visual fields) and brain imaging may be misleading, and suggest an idiopathic cause without high resolution MRI using the new generation scanners.328,355

Prognosis

Frequency, severity and response to treatment vary considerably from good to intractable or progressive, mainly depending on the underlying cause and extent of the lesions.328

Management

AED treatment is similar to that for any other type for focal seizures, is usually effective and should be initiated as soon as possible.328 Carbamazepine is the drug of choice.

The postictal headache of occipital seizures may be related to serotonergic mechanisms and responds to oral sumatriptan. 405

Neurosurgery is performed for selective symptomatic cases and may be effective in around 70% of patients with 30% becoming seizure free.312,321,403,421

The Drug Treatment of Focal Epilepsies

The treatment of focal epilepsies of any cause begins first with AEDs. If this fails, neurosurgical options are now becoming more widely available and are often life saving for symptomatic and probably symptomatic epilepsies (see individual syndromes).

Existing evidence indicates that 15422–30%423 of those with newly diagnosed focal epilepsy (of any cause) fail to achieve reasonably sustained remission with optimal antiepileptic medication. The figure is significantly higher (35%) for those with symptomatic focal epilepsy.422 Of those failing to respond, 25–50% develop intractable disease, that is continuation of seizures beyond 2–3 years, despite optimal AED treatment. In one large study, complex focal seizures were controlled in only 16–43% of patients, compared with 48–53% in those with only secondarily GTCS at 1 year.424

AED treatment in focal epilepsies has been detailed in recent books425–430 and reviews,431–445 although the conclusions of experts sometimes differ significantly. My recommendations, based on the procedures explained in Chapter 4 (page 59), are fairly pragmatic, combining evidence-based medicine with clinical experience. Details for each AED can be found in Chapter 14 in the pharmacopoeia (page 497).

Antiepileptic Drugs Effective for Focal Seizures

Carbamazepine and phenytoin are the superior old AEDs in the treatment of focal seizures. According to evidence-based medicine, all new AEDs entered into randomised controlled trials (RCT) have approximately equal efficacy to carbamazepine, phenytoin and valproate in controlling focal seizures, but are better tolerated.431,432,446 The reality in clinical practice often contradicts these conclusions for many reasons.431,447,448 It is extremely difficult to find a balance. There is a significant and rapidly changing swing with the increasing experience obtained from the clinical application of licensed new drugs and the introduction of new antiepileptic agents. The following may be applicable at the present time.

Evidence-Based Medicine

Overall, RCTs in patients with focal seizures with or without secondarily GTCS have shown the following.

  • In head-to-head comparisons of old AEDs (phenobarbitone, primidone, phenytoin and carbamazepine), overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbitone and lowest with primidone.424 Carbamazepine provided complete control of focal seizures more often than primidone or phenobarbitone. The control of GTCS and the proportion of patients rendered seizure free (48–63%) did not differ significantly with the various AEDs. The differences in the failure rates were explained primarily by their adverse reactions.424
  • In head-to-head comparisons of carbamazepine with valproate, carbamazepine provided better control of complex focal seizures and had fewer long-term adverse effects than valproate.449 Both drugs were comparably effective for the control of secondarily GTCS.449 These conclusions have been confirmed in a recent meta-analysis report.450
  • “The new AEDs gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide are of nearly equal efficacy to carbamazepine, phenytoin and valproate (phenobarbitone and clobazam have not been used in recent RCT).”431,432,446 Comparatively, topiramate and levetiracetam have the highest efficacy, while lamotrigine and gabapentin are the least efficacious (Table 12.4 and Figure 12.20).
Table 12.4. Order of priority of new AEDs in intractable focal epilepsies.

Table 12.4

Order of priority of new AEDs in intractable focal epilepsies.

Figure 12.20. Comparison of odds ratios, with 95% confidence intervals, for the efficacy (responder rates) and tolerability (withdrawal rates) of new AEDs in a meta-analysis of published RCTs.

Figure 12.20

Comparison of odds ratios, with 95% confidence intervals, for the efficacy (responder rates) and tolerability (withdrawal rates) of new AEDs in a meta-analysis of published RCTs. The numbers of patients included in the (more...)

New AEDs are “better tolerated, with few adverse effects, minimal drug interactions, and a broad spectrum of activity”.431,432,446,458 However, this generalisation needs clarification (Table 12.4). Only a few of the new AEDs, such as levetiracetam, fulfil these conclusions. Conversely, certain other new AEDs, such as topiramate have adverse reactions that are worse than those of carbamazepine. Lamotrigine, oxcarbamazepine and topiramate have clinically significant drug–drug interactions. Gabapentin and tiagabine have a narrow spectrum of antiepileptic activity and they are contraindicated in generalised epilepsies (Table 12.4).

There are no direct head-to-head comparisons between new AEDs. Therefore, the comparative efficacy and tolerability of new AEDs is deduced from meta-analyses of RCTs (Figure 12.21).430,459–461 A reliable way of comparing new AEDs is to display the odds ratios for efficacy and tolerability in the same graph (Figure 12.20). Efficacy is assessed by the odds ratio for a 50% seizure reduction, which is defined as the probability of a patient being a □50% responder with the test AED divided by the probability of being a □50% responder with placebo. The more effective the AED tested, the bigger is the numerical value of the odds ratio and the higher the position of the AED in the histogram in Figure 12.20. A numerical value of unity indicates that there is an equal probability of a patient being a □50% responder, either with the tested AED or placebo. The tolerability and safety of AEDs is usually assessed by the odds ratio of premature withdrawal from the RCT. AEDs with small odds ratios are better tolerated and further on the right in the histogram. An odds ratio of unity indicates that the probability for withdrawal is equal for the tested AED and the placebo.

Figure 12.21. Synaptic vesicle protein 2A, the binding site of levetiracetam.

Figure 12.21

Synaptic vesicle protein 2A, the binding site of levetiracetam. Levetiracetam is the first and only AED found to bind to synaptic vesicle protein 2A (SV2A). SV2A binding inhibits abnormal bursting in epileptic circuits, which (more...)

Clinical Practice in Developed Countries

Old Antiepileptic Drugs in Developed Countries

Carbamazepine is the superior drug for controlling focal seizures in more than 70% of patients (10% of patients develop idiosyncratic reactions). Valproate, a superior drug in generalised epilepsies, is inferior in focal epilepsies, with significant concerns in the treatment of women. Use of phenytoin, which is as effective as carbamazepine, is falling dramatically, mainly because of chronic toxicity. Phenobarbitone and primidone, which are less efficacious, have been practically eliminated, mainly because of their adverse effects on cognition. Clobazam, though often highly beneficial in selective cases, is rarely used as continuous AED treatment and it is not licensed in the USA.

New Antiepileptic Drugs in Developed Countries

Oxcarbazepine, which is probably of equal efficacy to carbamazepine and possibly with less idiosyncratic reactions, is gaining some ground.474 Levetiracetam has become increasingly more popular, because of a combined high efficacy, comparative poverty of adverse reactions, lack of drug–drug interactions and rapid titration. Topiramate is very efficacious, but with serious and numerous adverse reactions that reduce its value. Lamotrigine is relatively widely used despite relatively low efficacy in RCTs, often severe idiosyncratic reactions and drug–drug interactions. Gabapentin has very weak antiepileptic efficacy and rarely achieves satisfactory control of seizures,430 but it is has become popular in the USA, where it has been promoted for many off-label uses, mainly neurogenic pain. Zonisamide has been used widely in Japan in intractable focal epilepsies. Tiagabine is used cautiously, because of fears of adverse reactions, such as non-convulsive status epilepticus. Vigabatrin has been practically discarded in the treatment of epilepsies, because of common and often irreversible visual field defects. Currently, the use of vigabatrin is limited to infantile spasms.

Clinical Practice in Developing Countries

Phenytoin, carbamazepine and phenobarbitone are by far the most common main antiepileptic agents for treating focal epilepsies, either as monotherapy or polytherapy).

Note on the Use of Valproate and Clobazam in Focal Epilepsies

Valproate is the superior AED for generalised epilepsies, but its use as monotherapy in focal epilepsies is debated. The assessment of RCTs450 that valproate is of nearly equal efficacy to carbamazepine in focal epilepsies contradicts the experience in clinical practice that valproate is not the appropriate AED for focal seizures. There are many reasons for this contradiction. Firstly, in RCTs, “Misclassification of patients may have confounded the results … The age distribution of adults classified as having generalised seizures indicated that significant numbers of patients may have had their seizures misclassified.”450 Secondly, “systematic reviews cannot up-grade poor primary research. Also, a major hurdle is that of publication bias, as trials with a positive result are more likely to be published than those with a negative result.462 It is not surprising that a review of trials with positive results will come up with a positive answer.”460

Personally, after consistent failures to introduce valproate as monotherapy in focal seizures, I rarely use it and only adjunctively in patients with focal and secondarily GTCS because of the following: effective required doses of valproate are much higher for focal than generalised epilepsies; side effects, particularly in some women, make its use extremely problematic;.currently, there are other more effective and safer drugs for focal seizures.

Clobazam in the treatment of focal epilepsies

Based on recent evidence, clobazam is a very useful AED both as monotherapy and polytherapy, though it is not licensed in the USA.463–473 It is neglected in current clinical practice mainly because it is erroneously considered of high dependence for all patients, of similar effectiveness regarding seizure type to that of clonazepam and because it is a benzodiazepine.

Clobazam is a very useful drug that should be tried in all intractable patients with focal seizures that fail to respond to other AEDs. Tolerance to clobazam has been overemphasised. The truth is in between and many patients may remain seizure free despite continuing use.464,473

A 23-year-old man with intractable temporal lobe epilepsy failed to respond to any appropriate medication. While waiting for neurosurgical evaluation, 20 mg of clobazam nocte was added with a miraculous effect. He has remained seizure free for 7 years.

Monotherapy of Focal Epilepsies

Monotherapy is the primary aim in all, and therefore also focal, epilepsies.

Carbamazepine remains the first choice AED in focal seizures, but over 10% of patients develop acute idiosyncratic reactions (mainly rash). In numerous comparative studies, no other drug showed better efficacy than carbamazepine in focal seizures, although some new AEDs were better tolerated.

If treatment with carbamazepine in maximal tolerated doses fails, other pragmatic options include, of the old AEDs, phenytoin and, of the new AEDs, oxcarbazepine, levetiracetam, lamotrigine, topiramate and zonisamide (in order of preference). Personally, I also use clobazam in selected cases and I do not recommend valproate.

Phenytoin, despite its high efficacy, may not be tolerated by 10–20% of patients, because of idiosyncratic reactions, which may be fatal in exceptional cases. Long-term use is associated with unacceptable adverse reactions, including dysmorphic features.

Phenobarbitone and primidone are still very useful AEDs, particularly when cost is of concern. Their use is often barred by cognitive adverse reactions.

All new AEDs have shown a variable degree of efficacy (Figure 12.20), tolerability (Figure 12.20), safety profile, pharmacokinetics and drug–drug interactions, which should be taken into account when choosing one drug over another and which may be in the following order of priority: oxcarbazepine, levetiracetam, lamotrigine, topiramate, gabapentin and zonisamide.

Oxcarbazepine should probably be the drug of first choice by virtue of similar efficacy to carbamazepine, evidence-based documentation and length of experience; it is the first of the new AEDs to achieve FDA approval as monotherapy in focal seizures.

Of all other new AEDs only levetiracetam, lamotrigine and topiramate have the potential to be monotherapy in focal seizures.

Rational Polytherapy

Rational polytherapy* is often needed for the treatment of intractable focal epilepsies. The decision for polytherapy should first examine the possible/probable reasons why the monotherapy failed. These should thoroughly examine the following possibilities, which often require re-evaluation of the diagnosis (genuine epileptic seizures? and what type of seizures?).

  • The patient does not suffer from epileptic seizures.
  • The patient has both genuine epileptic and non-epileptic seizures.
  • The patient has generalised seizures and not focal seizures.
  • The AED used as monotherapy was not suitable for the particular type of seizures or had weak efficacy.

Non-compliance, which varies from unwillingness to take medication to occasionally forgetting or missing the AED dose. The latter is often improved with the use of AED-monitored dosage systems, which are widely available through pharmacies. These are useful even for patients who comply well, but who often may be uncertain whether or not they have taken their medication.

Important note

* The word “rational” has been used in conjunction with “polytherapy” in order to emphasise that this can also be irrational and hazardous if a diagnosis is incorrect and anti-epileptic drug indications/contraindications are violated.475 Conversion from polytherapy to monotherapy should also be rational.476

In polytherapy, initially, a second drug is added to the first line agent, which had demonstrated acceptable but insufficient efficacy, tolerability or both in monotherapy. Adding a new AED with another one to three AEDs that have already partially or totally failed or have made the situation worse is a formidable physician’s task for a disappointed and frustrated patient. The choice of a second or sometimes a third AED depends on many factors such as efficacy, adverse effects, interactions with other drugs and mode of action (Table 12.4). Polytherapy with more than three drugs is discouraged because adverse reactions become more prominent with little if any seizure improvement.

Of the old AEDs, carbamazepine, phenytoin, valproate and phenobarbital (in that order of importance and priority) are the most valuable either as monotherapy or polytherapy and particularly when cost is of concern.

Carbamazepine is currently the gold standard for controlling focal seizures in more than 70% of patients (10% of the patients develop idiosyncratic reactions). Valproate, the gold standard in generalised epilepsies, is inferior in focal epilepsies, with significant concerns in the treatment of women. The usage of phenytoin, which is as effective as carbamazepine, is dramatically decreasing because of mainly chronic toxicity. Phenobarbitone and primidone, which are less efficacious, have been practically eliminated in developed countries, mainly because of their adverse effects on cognition.

Of the new AEDs, the consensus, including the recent American QS&TTA assessment,477 is that all of them are appropriate for adjunctive treatment in refractory focal epilepsies with or without secondarily GTCS.

Clinical note

It is appropriate to use gabapentin, lamotrigine, tiagabine, topiramate, oxcarbazepine, levetiracetam and zonisamide as add-on therapy in patients with refractory focal epilepsy.477

Guidance that gives the physician a list of options is unsatisfactory in practice. The clinician’s important question is:

‘In what order of priority the new AEDs should be used?’

The ideal profile of an antiepileptic drug for polytherapy purposes478 is that it:

  1. is effective
  2. has a low incidence of adverse effects
  3. causes no pharmacokinetic interactions
  4. favourably combines with drugs with different mechanisms of action
  5. needs minimal laboratory monitoring
  6. needs as little as possible titration.

Thus, the order of priority of the new add-on AED is determined by the following factors.

  • Strength of efficacy. The more efficacious a drug the more likely it is to control seizures and, if successful, withdrawal of other concomitant AEDs may be possible without losing seizure control and, in some cases, with improved seizure control (Figure 12.20).476 Seizure-free status is the ultimate, often achievable, goal of treatment and this should be precisely evaluated in any RCT and relevant formal practice parameter recommendations. 479
  • Safety and tolerability. This includes adverse reactions and particularly those that may be serious and may outweigh any beneficial effect achieved by a reduction in seizures (Table 12.4 and Figure 12.20). Topiramate is probably the worst of all new broad spectrum AEDs because of multiple and severe adverse reactions.
  • Interactions with other antiepileptic drugs, whether pharmacokinetic, pharmacodynamic or both, are particularly unwanted in polytherapy (Table 12.4).478 Raising the levels of concomitant AEDs and pharmacodynamic interactions may lead to toxic effects. Conversely, decreasing their levels may increase and worsen seizures causing a vicious circle in clinical management. With the exception of levetiracetam and454 gabapentin, all other new AEDs exhibit sometimes complex undesirable drug–drug interactions.453 Lamotrigine is amongst the worst of all new AEDs from that point. It requires different dosage and titration schemes when combined with hepatic enzyme-inducers and when combined with valproate. Concomitant administration of carbamazepine with lamotrigine enhances each drug’s side-effect profile as the result of pharmacodynamic interactions.
  • Different mechanisms of action in relation to other concurrent AEDs (Table 4.5, page 70).478,480 Antiepileptic drug–drug interactions may be purely additive, antagonistic or synergistic. AEDs with the same mechanism of action would be expected to be additive, while combining AEDs with different mechanisms of action may have synergistic efficacy.478,480 A review of clinical studies suggested that a combination of a sodium channel blocker with a drug that increases the GABAergic neurotransmission or that has multiple mechanisms is generally more effective than a combination of two sodium channel blockers.480 An AED is unlikely to have better success and more likely to have additive adverse reactions if added to another AED with the same mechanism of action.480 Levetiracetam appears to have a unique mode of action (Figure 12.21).
  • Need for less laboratory monitoring (Table 12.4). This refers firstly to monitoring of the serum AED levels of the added AED or the co-medications that may be affected, such as with lamotrigine or topiramate added to carbamazepine and, secondly, blood or other tests needed for detecting possible adverse drug reactions such as hypernatraemia with oxcarbazepine, metabolic acidosis for topiramate and zonisamide. More laboratory testing may mean less compliance, more expenses and more uncomfortable situations for patients.
  • The need for as little as possible titration (Table 12.4). Very slow titration may mean more seizures that may also be traumatic. Levetiracetam and gabapentin are nearly ideal from that point of view with their starting dose often equalling the effective maintenance dose. Conversely, lamotrigine and topiramate are inferior requiring 6–8 weeks of low dose and slow titration in order to reach reasonable therapeutic levels.

Taking all these parameters together levetiracetam is much superior to all other new AEDs (Tables 4.3, 4.4, 4.5, 4.6, 4.7 and 12.4 and Figure 12.20).

Levetiracetam

  • It is highly efficacious and has the most favourable ‘responder-withdrawal ratio’ of any other new AED (Figure 12.20 and Table 12.4).433,481 It reduces the frequency of simple and complex focal seizures and demonstrates a specific, independent reduction of secondarily GTCS. 482 Furthermore, in RCTs of intractable focal epilepsies the highest percentage of seizure free status was achieved with levetiracetam (9%) than any other of the new AEDs (0–5%). In the largest single-tertiary centre cohort of 811 patients with ‘chronic epilepsy’ taking levetiracetam, almost half of patients achieved a period of reduction in seizure frequency of □ 50%, with nearly one in five achieving a period of seizure freedom.483 Two-thirds of patients were continuing levetiracetam therapy at last follow-up. Impressively, seizure freedom was attained in 120/654 (18%) patients with cryptogenic or symptomatic focal epilepsy and 15/68 (22%) patients with IGE. Forty-six patients achieved levetiracetam monotherapy, and 26 of these had periods of seizure freedom ranging from 2–35 months (mean 13 months, median 11 months).483
  • It is considered as one of the most adverse reaction-free AED.484
  • The regulatory approved starting dose of 1000 mg/day is often therapeutic.
  • It does not have drug–drug interactions with concomitant medications. 453,485 It does not influence other AEDs in a clinically meaningful way and, conversely, other drugs do not interfere with the pharmacokinetics of levetiracetam.
  • It has a novel mechanism of action, which is different to all other old and new AEDs (Figure 12.21).
  • The need for laboratory tests is minimal if any.
Patient note

A 25-year-old woman had surgery for drug-resistant focal epilepsy due to left temporal lobe cavernoma at age 21 years. There was no improvement: she continued having four complex focal seizures per week and one GTCS per month despite appropriate combinations of all available AEDs being tried. A breakthrough in her life came when levetiracetam was added. She is now seizure free and obtained her driving licence on 1500 mg of levetiracetam daily and carbamazepine at reducing doses of 200 mg twice daily (case of Professor J. W. A. S. Sander).

Next to levetiracetam, the other new AEDs are in the following order of priority.

  1. Lamotrigine is one of the best AEDs regarding cognitive adverse effects, but is of low efficacy in RCTs of refractory patients with focal seizures. Frequent idiosyncratic reactions, which rarely may be fatal, are a realistic threat.486 Other significant disadvantages are drug-drug interactions including with hormonal contraception and the effect of pregnancy on lamotrigine plasma concentration 487 and slow titration.
  2. Topiramate, despite its significant efficacy, is characterised by frequent and sometimes serious adverse reactions such as nephrolithiasis, open angle glaucoma, hypohidrosis, metabolic acidosis, weight loss and language dysfunction.452 Metabolic acidosis in children may have a predictable detrimental growth and bone-related sequelae in long-term use. It is the worst tolerated AED in comparative RCTs (Figure 12.20). Drug-drug interactions including hormonal contraception are an additional disadvantage.
  3. Oxcarbazepine is amongst the first choice AEDs as monotherapy and it is the first of the new AEDs to achieve FDA approval for this indication in children. However, oxcarbazepine does not have high priority in co-medication with carbamazepine and phenytoin because of drug–drug interactions and added adverse reactions.
  4. Gabapentin is of very low efficacy in RCTs (Figure 12.20) and the clinical experience of most epileptologists with gabapentin,451 which I share, is disappointing.
Clinical note

The therapeutic efficacy of gabapentin is weak in relation to other AEDs, the number of responders is disappointingly low even when higher doses are used and it is unusual for patients with severe focal epilepsies to derive much benefit. 451

  1. Zonisamide: one of the most popular drugs in Japan but with significant drug-drug interactions and side effects some of which may be severe such hypohidrosis and hyperthermia or Stevens-Johnson syndrome. Nephrolitiasis occurred in 4% of patients in a USA study.488
  2. Tiagabine: treatment emergent non-convulsive status epilepticus has been reported in a significant number of patients. Its role is probably in the treatment of severe forms of focal epilepsies that failed to respond to other AEDs combinations. It is contraindicated in IGEs.
  3. Vigabatrin: Its use in epilepsies, other than West syndrome, is very restricted due to the high risk of irreversible visual field defects. It is contraindicated in IGEs. Tiagabine and vigabatrin are two GABAergic drugs that are contraindicated in IGEs. They induce (not treat) absences and absence status epilepticus.479,489

Pregabalin

It is probably too early to make any predictions for the role of pregabalin in the treatment of focal epilepsies. However, the high incidence of weight gain490 (consider the decline in the use of valproate because of this side effect and its causative relation with polycystic ovaries in women), treatment emergent myoclonic jerks 490,491 and similarities with gabapentin492 are not promising signs.

Weight gain appears to be significant even in RCTs of short duration involving active treatment with pregabalin. In one such RCT mean weight gain from baseline to termination (12 weeks) appeared to be dose related and ranged from 0.50 kg in the 50 mg/day treatment group to 2.28 kg in the 600 mg/day treatment group (12.4% of patients).493 Future RCTs are expected to determine whether weight gain with pregabalin is progressive with continuing use of this agent.

The pro-myoclonic action of pregabalin is even more disquieting. Four of 19 patients (21%) with intractable focal seizures developed myoclonic jerks in a RCT when pregabalin was added to other AEDs.491 Though the prevalence of pregabalin-induced myoclonus was found to be much lower (2% of patients) in another recent RCT (2% of patients with focal seizures)490 this is a warning sign against its use in generalised epilepsies (in which myoclonus is often a prominent symptom to treat) or at its best it indicates a narrow antiepileptic spectrum of pregabalin similar to that of gabapentin.

References

1.
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389–99. [PubMed: 2502382]
2.
Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42:796–803. [PubMed: 11422340]
3.
Hauser WA. Incidence and prevalence of epilepsy. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 47–57.
4.
Crawford PM. Epidemiology of intractable focal epilepsy. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 25–40.
5.
Wiebe S. Epidemiology of temporal lobe epilepsy. Can J Neurol Sci. 2000;27(Suppl 1):S6–10. [PubMed: 10830320]
6.
Sisodiya SM. Malformations of cortical development: burdens and insights from important causes of human epilepsy. Lancet Neurol. 2004;3:29–38. [PubMed: 14693109]
7.
Mathern GW, Babb TL, Pretorius JK, Melendez M, Levesque MF. The pathophysiologic relationships between lesion pathology, intracranial ictal EEG onsets, and hippocampal neuron losses in temporal lobe epilepsy. Epilepsy Res. 1995;21:133–47. [PubMed: 7588588]
8.
Babb TL. Synaptic reorganizations in human and rat hippocampal epilepsy. Adv Neurol. 1999;79:763–79. [PubMed: 10514862]
9.
Wolf HK, Campos MG, Zentner J, Hufnagel A, Schramm J, Elger CE, et al. Surgical pathology of temporal lobe epilepsy. Experience with 216 cases. J Neuropathol Exp Neurol. 1993;52:499–506. [PubMed: 8360703]
10.
Wolf HK, Zentner J, Hufnagel A, Campos MG, Schramm J, Elger CE, et al. Morphological findings in temporal lobe epilepsy: experience with 216 consecutive surgical specimens. Verh Dtsch Ges Pathol. 1994;78:438–42. [PubMed: 7534018]
11.
Wolf HK, Aliashkevich AF, Blumcke I, Wiestler OD, Zentner J. Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy. A quantitative analysis of 70 surgical specimens. Acta Neuropathol. (Berl) 1997;93:606–10. [PubMed: 9194900]
12.
Bouchet C, Cazauvieilh JB. De l’épilepsie considéré dans ses rapports avec l’aliénation mentale. Arch Gen Med. 1825;9:510–42.
13.
Gowers WR. Their causes, symptoms and treatment. London: Churchill JA; 1881. Epilepsies and other chronic convulsive diseases.
14.
Jackson JH. On a particular variety of epilepsy (“intellectual aura”), one case with symptoms of organic brain disease. Brain. 1888;11:179–207.
Taylor J, editor. Selected writings of John Hughlings Jackson. London: Hodder and Stoughton; 1958. pp. 385–405.
15.
Jackson JH, Colman WS. Case of epilepsy with tasting movements and “dreaming state”-very small patch of softening in the left uncinate gyrus. Brain. 1898;21:580–90.
Taylor J, editor. Selected writings of John Hughlings Jackson. London: Hodder and Stoughton; 1958. pp. 458–463.
16.
Holmes G. Sabill memorial oration on focal epilepsy. Lancet. 1927;i:957–62.
17.
Penfield W, Kristiansen K. Epileptic seizure patterns. Springfield, IL: Charles C Thomas; 1951.
18.
Lennox WG, Lennox MA. Epilepsy and related disorders. Boston: Little, Brown & Co; 1960.
19.
Ajmone-Marsan C, Ralston BL. A clinical-electrographic analysis of metrazol-induced attacks. Springfield, Illinois: Charles C. Thomas; 1957. The epileptic seizure:its functional morphology and diagnostic significance.
20.
Baldwin M, Bailey P. Temporal lobe epilepsy. Springfield, Ill: Charles C. Thomas; 1958.
21.
Ajmone-Marsan C, Abraham K. A seizure atlas. Electroencephalogr Clin Neurophysiol. 1960;(Suppl 15):1–215.
22.
Aird RB, Venturini AM, Spielman PM. Antecedents of temporal lobe epilepsy. Arch Neurol. 1967;16:67–73. [PubMed: 4960767]
23.
Aird RB, Crowther DL. Temporal lobe epilepsy in childhood. Clinical expressions observed in 125 affected children. Clin Pediatr. 1970;9:409–15. [PubMed: 5433635]
24.
Currie S, Heathfield KW, Henson RA, Scott DF. Clinical course and prognosis of temporal lobe epilepsy. A survey of 666 patients. Brain. 1971;94:173–90. [PubMed: 5552161]
25.
Daly DD. Ictal clinical manifestations of complex partial seizures. Adv Neurol. 1975;11:57–83. [PubMed: 1217573]
26.
Penry JK. Perspectives in complex partial seizures. Adv Neurol. 1975;11:1–14. [PubMed: 814796]
27.
Penfield W. The mystery of the mind. Princeton, New Jersey: Princeton University Press; 1975.
28.
Gloor P, Olivier A, Quesney LF, Andermann F, Horowitz S. The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Ann Neurol. 1982;12:129–44. [PubMed: 7125603]
29.
Ounsted C, Lindsay J, Richards P. A biographical study 1948–1986. London: MacKeith Press; 1988. Temporal lobe epilepsy.
30.
Bruton CJ. The neuropathology of temporal lobe epilepsy. Oxford: Oxford Press; 1988.
31.
Gloor P. Experiential phenomena of temporal lobe epilepsy. Facts and hypotheses. Brain. 1990;113:1673–94. [PubMed: 2276040]
32.
Wieser HG. Ictal manifestations of temporal lobe seizures. Adv Neurol. 1991;55:301–15. [PubMed: 2003413]
33.
Bancaud J, Brunet-Bourgin F, Chauvel P, Halgren E. Anatomical origin of deja vu and vivid ‘memories’ in human temporal lobe epilepsy. Brain. 1994;117:71–90. [PubMed: 8149215]
34.
Kotagal P, Luders HO, Williams G, Nichols TR, McPherson J. Psychomotor seizures of temporal lobe onset: analysis of symptom clusters and sequences. Epilepsy Research. 1995;20:49–67. [PubMed: 7713060]
35.
Wieser HG. Electroclinical features of the psychomotor seizure:A stereoelectroencephalographic study of ictal symptoms and chronotopographical seizure patterns including clinical effects of intracerebral stimulation. Stuttgard: Gustav Fischer; 1983.
36.
Luders H, Lesser RP. Electroclinical syndromes. Berlin Heidelberg: Springer-Verlag; 1987. Epilepsy.
37.
Engel J Jr, Williamson PD, Wieser HG. Mesial temporal lobe epilepsy. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 2417–26.
38.
Williamson PD, Thadani VM, French JA, Darcey TM, Mattson RH, Spencer SS, et al. Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics. Epilepsia. 1998;39:1182–8. [PubMed: 9821982]
39.
Williamson PD. Mesial temporal lobe epilepsy. In: Gilman S, editor. Medlink. San Diego CA: Arbor Publishing; 2004.
40.
French JA, Williamson PD, Thadani VM, Darcey TM, Mattson RH, Spencer SS, et al. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Ann Neurol. 1993;34:774–80. [PubMed: 8250525]
41.
Gonzalez-Pal S, Faure A, Quintana J, Fabelo R, Dominguez ME, Gomez-Plasencia R, et al. Frontal lobe dysfunction in patients with epilepsy and chronic psychosis. Rev Neurol. 1999;28:219–23. [PubMed: 10714280]
42.
Sperling MR, Lieb JP, Engel J Jr, Crandall PH. Prognostic significance of independent auras in temporal lobe seizures. Epilepsia. 1989;30:322–31. [PubMed: 2721465]
43.
Sperling MR, O’Connor MJ. Auras and subclinical seizures: characteristics and prognostic significance. Ann Neurol. 1990;28:320–8. [PubMed: 2241115]
44.
van Buren JM. The abdominal aura: a study of abdominal sensations occurring in epilepsy and produced by depth stimulation. Electroencephalogr Clin Neurophysiol. 1963;15:1–19. [PubMed: 13995971]
45.
Duncan JS, Sagar HJ. Seizure characteristics, pathology, and outcome after temporal lobectomy. Neurology. 1987;37:405–9. [PubMed: 3822133]
46.
Gastaut H. Part I:Definitions. Geneva: World Health Organisation; 1973. Dictionary of epilepsies.
47.
Jackson JH. On the anatomical, physiological and pathological investigation of the epilepsies. West Riding Lunatic Asylum Medical Reports. 1873;3:315–39.
Taylor J, editor. Selected writings of John Hughlings Jackson. London: Hodder and Stoughton; 1958. pp. 90–111.
48.
Jackson JH. On right or left-sided spasm at the onset of epileptic paroxysms, and on crude sensation warnings, and elaborate mental states. Brain. 1880;iii:192.
Taylor J, editor. Selected writings of John Hughlings Jackson. London: Hodder and Stoughton; 1958. pp. 308–317.
49.
Penfield W, Perot P. The brain’s record of auditory and visual experience. Brain. 1963;86:595–696. [PubMed: 14090522]
50.
Adachi N, Koutroumanidis M, Elwes RD, Polkey CE, Binnie CD, Reynolds EH, et al. Interictal 18FDG PET findings in temporal lobe epilepsy with deja vu. J Neuropsychiatry Clin Neurosci. 1999;11:380–6. [PubMed: 10440015]
51.
Penfield W, Jasper HH. Epilepsy and the functional anatomy of the human brain. Boston: Little, Brown & Co; 1954.
52.
Wieser HG, Mazzola G. Musical consonances and dissonances: are they distinguished independently by the right and left hippocampi? Neuropsychologia. 1986;24:805–12. [PubMed: 3808288]
53.
Wieser HG, Walter R. Untroubled musical judgement of a performing organist during early epileptic seizure of the right temporal lobe. Neuropsychologia. 1997;35:45–51. [PubMed: 8981376]
54.
Acharya V, Acharya J, Luders H. Olfactory epileptic auras. Neurology. 1998;51:56–61. [PubMed: 9674778]
55.
Ebner A, Kerdar MS. Olfactory and gustatory auras. In: Luders HO, Noachtar S, editors. Epileptic seizures. Pathophysiology and clinical semiology. New York: Churchill Livingstone; 2000. pp. 313–9.
56.
Chen C, Shih YH, Yen DJ, Lirng JF, Guo YC, Yu HY, et al. Olfactory auras in patients with temporal lobe epilepsy. Epilepsia. 2003;44:257–60. [PubMed: 12558584]
57.
Badalian LO, Temin PA, Mukhin KI, Askochenskaia TI, Shnaidman RV, Korshunov SV. Temporal-lobe epilepsy with psychosensory and gustatory attacks. Zh Nevropatol Psikhiatr Im S S Korsakova. 1993;93:17–9. [PubMed: 8042352]
58.
Hausser-Hauw C, Bancaud J. Gustatory hallucinations in epileptic seizures. Electrophysiological, clinical and anatomical correlates. Brain. 1987;110:339–59. [PubMed: 3105808]
59.
Nagy Z, Esiri MM. Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy. Exp Neurol. 1998;150:240–7. [PubMed: 9527893]
60.
Yanez A, Morales E, Galdames D, Aguilera L, Faure E, Ortiz V, et al. Temporal lobectomy in refractory partial epilepsy. Report of 4 cases. Rev Med Chil. 1994;122:186–92. [PubMed: 8085084]
61.
Lance JW. Simple formed hallucinations confined to the area of a specific visual field defect. Brain. 1976;99:719–34. [PubMed: 828866]
62.
Kolmel HW. Visual illusions and hallucinations. Baillieres Clinical Neurology. 1993;2:243–64. [PubMed: 8137001]
63.
Baumgartner C, Groppel G, Leutmezer F, Aull-Watschinger S, Pataraia E, Feucht M, et al. Ictal urinary urge indicates seizure onset in the nondominant temporal lobe. Neurology. 2000;55:432–4. [PubMed: 10932282]
64.
Manford M, Fish DR, Shorvon SD. An analysis of clinical seizure patterns and their localizing value in frontal and temporal lobe epilepsies. Brain. 1996;119:17–40. [PubMed: 8624679]
65.
Dantas FG, Yacubian EM, Jorge CL, Pedreira CC, Bueno JF, Valerio RM. Clinical and EEG analysis of mesial and lateral temporal lobe seizures. Arq Neuropsiquiatr. 1998;56:341–9. [PubMed: 9754413]
66.
Fakhoury T, Abou-Khalil B, Peguero E. Differentiating clinical features of right and left temporal lobe seizures. Epilepsia. 1994;35:1038–44. [PubMed: 7925149]
67.
Duchowny M, Jayakar P, Resnick T, Levin B, Alvarez L. Posterior temporal epilepsy: electroclinical features. Ann Neurol. 1994;35:427–31. [PubMed: 8154869]
68.
Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde BW, Engel J Jr. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia. 2001;42:1212–8. [PubMed: 11580774]
69.
Jackson HJ. On temporary mental disorders after epilepsy paroxysms. West Riding Lunatic Asylum Medical Reports. 1875;v
Taylor J, editor. Selected writings of John Hughlings Jackson. London: Hodder and Stoughton; 1958. pp. 119–134.
70.
Yen DJ, Su MS, Yiu CH, Shih, Kwan SY, Tsai CP, et al. Ictal speech manifestations in temporal lobe epilepsy: a video- EEG study. Epilepsia. 1996;37:45–9. [PubMed: 8603623]
71.
Panayiotopoulos CP. A clinical guide to epileptic syndromes and their treatment. Oxford: Bladon Medical Publishing; 2002.
72.
Hecker A, Andermann F, Rodin EA. Spitting automatism in temporal lobe seizures with a brief review of ethological and phylogenetic aspects of spitting. Epilepsia. 1972;13:767–72. [PubMed: 4509171]
73.
Sussman NM, Jackel RA, Kaplan LR, Harner RN. Bicycling movements as a manifestation of complex partial seizures of temporal lobe origin. Epilepsia. 1989;30:527–31. [PubMed: 2792028]
74.
Remillard GM, Andermann F, Testa GF, Gloor P, Aube M, Martin JB, et al. Sexual ictal manifestations predominate in women with temporal lobe epilepsy: a finding suggesting sexual dimorphism in the human brain. Neurology. 1983;33:323–30. [PubMed: 6681877]
75.
Wieser HG, Hajek M, Gooss A, Aguzzi A. Mesial temporal lobe epilepsy syndrome with hippocampal and amygdala sclerosis. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 131–58.
76.
Elger CE. Semeiology of temporal lobe seizures. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 63–8.
77.
Serles W, Pataraia E, Bacher J, Olbrich A, Aull S, Lehrner J, et al. Clinical seizure lateralization in mesial temporal lobe epilepsy: differences between patients with unitemporal and bitemporal interictal spikes. Neurology. 1998;50:742–7. [PubMed: 9521267]
78.
Abou-Khalil B, Welch L, Blumenkopf B, Newman K, Whetsell WO Jr. Global aphasia with seizure onset in the dominant basal temporal region. Epilepsia. 1994;35:1079–84. [PubMed: 7925155]
79.
Esclapez M, Houser CR. Up-regulation of GAD65 and GAD67 in remaining hippocampal GABA neurons in a model of temporal lobe epilepsy. J Comp Neurol. 1999;412:488–505. [PubMed: 10441235]
80.
Fernandez Torre JL, Alarcon G, Binnie CD, Polkey CE. Comparison of sphenoidal, foramen ovale and anterior temporal placements for detecting interictal epileptiform discharges in presurgical assessment for temporal lobe epilepsy. Clin Neurophysiol. 1999;110:895–904. [PubMed: 10400203]
81.
Kotagal P, Luders H, Morris HH, Dinner DS, Wyllie E, Godoy J, et al. Dystonic posturing in complex partial seizures of temporal lobe onset: a new lateralizing sign. Neurology. 1989;39:196–201. [PubMed: 2915789]
82.
Benbadis SR, Kotagal P, Klem GH. Unilateral blinking: a lateralizing sign in partial seizures. Neurology. 1996;46:45–8. [PubMed: 8559419]
83.
Oestreich LJ, Berg MJ, Bachmann DL, Burchfiel J, Erba G. Ictal contralateral paresis in complex partial seizures. Epilepsia. 1995;36:671–5. [PubMed: 7555983]
84.
Ansakorpi H, Korpelainen JT, Suominen K, Tolonen U, Myllyla VV, Isojarvi JI. Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy. Epilepsia. 2000;41:42–7. [PubMed: 10643922]
85.
O’Donovan CA, Burgess RC, Lueders H. Autonomic auras. In: Luders HO, Noachtar S, editors. Epileptic seizures. Pathophysiology and clinical semiology. New York: Churchill Livingstone; 2000. pp. 320–35.
86.
Toichi M, Murai T, Sengoku A, Miyoshi K. Interictal change in cardiac autonomic function associated with EEG abnormalities and clinical symptoms: a longitudinal study following acute deterioration in two patients with temporal lobe epilepsy. Psychiatry Clin Neurosci. 1998;52:499–505. [PubMed: 10215011]
87.
Gleizer MA, Karlov VA. Autonomic dysfunction in patients with temporal lobe epilepsy. Zh Nevropatol Psikhiatr Im S S Korsakova. 1988;88:11–5. [PubMed: 3055770]
88.
Saleh Y, Kirchner A, Pauli E, Hilz MJ, Neundorfer B, Stefan H. Temporal lobe epilepsy: effect of focus side on the autonomic regulation of heart rate? Nervenarzt. 2000;71:477–80. [PubMed: 10919143]
89.
Schernthaner C, Lindinger G, Potzelberger K, Zeiler K, Baumgartner C. Autonomic epilepsy—the influence of epileptic discharges on heart rate and rhythm. Wien Klin. Wochenschr. 1999;111:392–401. [PubMed: 10413832]
90.
Blumhardt LD, Smith PE, Owen L. Electrocardiographic accompaniments of temporal lobe epileptic seizures. Lancet. 1986;1:1051–6. [PubMed: 2871334]
91.
Delamont RS, Julu PO, Jamal GA. Changes in a measure of cardiac vagal activity before and after epileptic seizures. Epilepsy Res. 1999;35:87–94. [PubMed: 10372561]
92.
Massetani R, Strata G, Galli R, Gori S, Gneri C, Limbruno U, et al. Alteration of cardiac function in patients with temporal lobe epilepsy: different roles of EEG-ECG monitoring and spectral analysis of RR variability. Epilepsia. 1997;38:363–9. [PubMed: 9070600]
93.
Scott CA, Fish DR. Cardiac asystole in partial seizures. Epilep Disord. 2000;2:89–92. [PubMed: 10954239]
94.
Baumgartner C, Olbrich A, Lindinger G, Pataraia E, Groppel G, Bacher J, et al. Regional cerebral blood flow during temporal lobe seizures associated with ictal vomiting: an ictal SPECT study in two patients. Epilepsia. 1999;40:1085–91. [PubMed: 10448820]
95.
Chen C, Yen DJ, Yiu CH, Shih YH, Yu HY, Su MS. Ictal vomiting in partial seizures of temporal lobe origin. Eur. Neurol. 1999;42:235–9. [PubMed: 10567822]
96.
Schauble B, Britton JW, Mullan BP, Watson J, Sharbrough FW, Marsh WR. Ictal vomiting in association with left temporal lobe seizures in a left hemisphere language-dominant patient. Epilepsia. 2002;43:1432–5. [PubMed: 12423396]
97.
Koutroumanidis M. Ictal vomiting in association with left temporal lobe seizures in a left hemisphere language-dominant patient. Epilepsia. 2003;44:1259. [PubMed: 12919403]
98.
Panayiotopoulos CP. Vomiting as an ictal manifestation of epileptic seizures and syndromes. J Neurol Neurosurg Psychiatr. 1988;51:1448–51. [PMC free article: PMC1032819] [PubMed: 3148690]
99.
Panayiotopoulos CP. Panayiotopoulos syndrome. Lancet. 2001;358:68–9. [PubMed: 11458931]
100.
Panayiotopoulos CP. Autonomic seizures and autonomic status epilepticus peculiar to childhood: diagnosis and management. Epilepsy Behav. 2004;5:286–95. [PubMed: 15145296]
101.
Tassinari CA, Riguzzi P, Rizzi R, Passarelli D, Volpi L. Gelastic seizures. In: Tuxhorn I, Holthausen H, Boenigk H, editors. Paediatric epilepsy syndromes and their surgical treatment. London: John Libbey & Comapny Ltd; 1997. pp. 429–46.
102.
Mitchell A, Penman MF. Temporal lobectomy: an increasingly viable option for seizure patients. Axone. 1989;10:69–71. [PubMed: 2466477]
103.
Risinger MW, Engel J Jr, Van Ness PC, Henry TR, Crandall PH. Ictal localization of temporal lobe seizures with scalp/sphenoidal recordings. Neurology. 1989;39:1288–93. [PubMed: 2797451]
104.
Brorson JR, Brewer K. St Paul and temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 1988;51:886–7. [PMC free article: PMC1033172] [PubMed: 3042917]
105.
Arroyo S, Lesser RP, Gordon B, Uematsu S, Hart J, Schwerdt P, et al. Mirth, laughter and gelastic seizures. Brain. 1993;116:757–80. [PubMed: 8353707]
106.
Gascon GG, Lombroso CT. Epileptic (gelastic) laughter. Epilepsia. 1971;12:63–76. [PubMed: 5282883]
107.
Lehtinen LO, Kivalo A. Laughter epilepsy. Acta Neurol Scand. 1965;41:255–8. [PubMed: 14319759]
108.
Jacome DE, McLain LW Jr, FitzGerald R. Postural reflex gelastic seizures. Arch Neurol. 1980;37:249–51. [PubMed: 7362494]
109.
Palmini AL, Gloor P, Jones-Gotman M. Pure amnestic seizures in temporal lobe epilepsy. Definition, clinical symptomatology and functional anatomical considerations. Brain. 1992;115:749–69. [PubMed: 1628200]
110.
Bauer J, Ghane Y, Flugel D, Wildt L, Stefan H. Etiology, follow-up and therapy of seizure clusters in temporal lobe epilepsy and catamenial epileptic seizures. Schweiz Arch Neurol Psychiatr. 1992;143:117–34. [PubMed: 1375777]
111.
Foldvary-Schaefer N, Falcone T. Catamenial epilepsy: pathophysiology, diagnosis, and management. Neurology. 2003;61:S2–15. [PubMed: 14504304]
112.
Grunewald RA, Aliberti V, Panayiotopoulos CP. Exacerbation of typical absence seizures by progesterone. Seizure. 1992;1:137–8. [PubMed: 1344329]
113.
Foldvary N, Lee N, Thwaites G, Mascha E, Hammel J, Kim H, et al. Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy. Neurology. 1997;49:757–63. [PubMed: 9305337]
114.
Antel SB, Li LM, Cendes F, Collins DL, Kearney RE, Shinghal R, et al. Predicting surgical outcome in temporal lobe epilepsy patients using MRI and MRSI. Neurology. 2002;58:1505–12. [PubMed: 12034787]
115.
Briellmann RS, Berkovic SF, Syngeniotis A, King MA, Jackson GD. Seizure-associated hippocampal volume loss: a longitudinal magnetic resonance study of temporal lobe epilepsy. Ann Neurol. 2002;51:641–4. [PubMed: 12112114]
116.
Duncan JS. Neuroimaging. In: Duncan JS, Sisodiya S, Smalls JE, editors. Epilepsy 2001. From science to patient. Oxford: Meritus Communications; 2001. pp. 173–216.
117.
Cendes F. Radiological evaluation of hippocampal sclerosis. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 571–94.
118.
Li LM, Caramanos Z, Cendes F, Andermann F, Antel SB, Dubeau F, et al. Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from extra-TLE using pattern analysis of magnetic resonance spectroscopic and volumetric data. Epilepsia. 2000;41:832–42. [PubMed: 10897154]
119.
Meierkord H, Shorvon S, Lightman S, Trimble M. Comparison of the effects of frontal and temporal lobe partial seizures on prolactin levels. Arch Neurol. 1992;49:225–30. [PubMed: 1536623]
120.
Malow BA, Selwa LM, Ross D, Aldrich MS. Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy. Epilepsia. 1999;40:1587–92. [PubMed: 10565587]
121.
Pataraia E, Lurger S, Serles W, Lindinger G, Aull S, Leutmezer F, et al. Ictal scalp EEG in unilateral mesial temporal lobe epilepsy. Epilepsia. 1998;39:608–14. [PubMed: 9637603]
122.
Cascino GD, Trenerry MR, So EL, Sharbrough FW, Shin C, Lagerlund TD, et al. Routine EEG and temporal lobe epilepsy: relation to long-term EEG monitoring, quantitative MRI, and operative outcome. Epilepsia. 1996;37:651–6. [PubMed: 8681897]
123.
Koutroumanidis M, Binnie CD, Panayiotopoulos CP. Positron emission tomography in partial epilepsies: the clinical point of view. Nucl Med Commun. 1998;19:1123–6. [PubMed: 9885801]
124.
Koutroumanidis M, Binnie CD, Elwes RD, Polkey CE, Seed P, Alarcon G, et al. Interictal regional slow activity in temporal lobe epilepsy correlates with lateral temporal hypometabolism as imaged with 18FDG PET: neurophysiological and metabolic implications. J Neurol Neurosurg Psychiatry. 1998;65:170–6. [PMC free article: PMC2170184] [PubMed: 9703166]
125.
Koutroumanidis M, Martin-Miguel C, Hennessy MJ, Akanuma N, Valentin A, Alarcon G, et al. Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome. Epilepsia. 2004;45:1351–67. [PubMed: 15509236]
126.
Sakai Y, Nagano H, Sakata A, Kinoshita S, Hamasaki N, Shima F, et al. Localization of epileptogenic zone in temporal lobe epilepsy by ictal scalp EEG. Seizure. 2002;11:163–8. [PubMed: 12018959]
127.
Sadler M, Desbiens R. Scalp EEG in temporal lobe epilepsy surgery. Can J Neurol Sci. 2000;27(Suppl 1):S22–S28. [PubMed: 10830323]
128.
Schulz R, Luders HO, Hoppe M, Tuxhorn I, May T, Ebner A. Interictal EEG and ictal scalp EEG propagation are highly predictive of surgical outcome in mesial temporal lobe epilepsy. Epilepsia. 2000;41:564–70. [PubMed: 10802762]
129.
Panayiotopoulos CP, Chroni E, Daskalopoulos C, Baker A, Rowlinson S, Walsh P. Typical absence seizures in adults: clinical, EEG, video-EEG findings and diagnostic/syndromic considerations. J Neurol Neurosurg Psychiatr. 1992;55:1002–8. [PMC free article: PMC1015282] [PubMed: 1469393]
130.
Hauser WA. The natural history of temporal lobe epilepsy. In: Luders HO, editor. Epilepsy surgery. New York: Raven Press; 1992. pp. 133–41.
131.
Engel J Jr, Wiebe S, French J, Sperling M, Williamson P, Spencer D, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. 2003;60:538–47. [PubMed: 12601090]
132.
Engel J Jr, Wiebe S, French J, Sperling M, Williamson P, Spencer D, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia. 2003;44:741–51. [PubMed: 12790886]
133.
Engel J Jr. Recent advances in surgical treatment of temporal lobe epilepsy. Acta Neurol Scand Suppl. 1992;140:71–80. [PubMed: 1441912]
134.
Wieser HG. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2004;45:695–714. [PubMed: 15144438]
135.
Engel J Jr, editor. Surgical treatment of the epilepsies. New York: Raven; 1993.
136.
Gil-Nagel A, Risinger MW. Ictal semiology in hippocampal versus extrahippocampal temporal lobe epilepsy. Brain. 1997;120:183–92. [PubMed: 9055806]
137.
Mohamed A, Luders HO. Magnetic resonance imaging in temporal lobe epilepsy: usefulness for the etiological diagnosis of temporal lobe epilepsy. Neurol Med Chir (Tokyo) 2000;40:1–15. [PubMed: 10721251]
138.
Hogan RE, Wang L, Bertrand ME, Willmore LJ, Bucholz RD, Nassif AS, et al. MRI-based high-dimensional hippocampal mapping in mesial temporal lobe epilepsy. Brain. 2004 [PubMed: 15231583]
139.
Frost JJ, Mayberg HS, Fisher RS, Douglass KH, Dannals RF, Links JM, et al. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol. 1988;23:231–7. [PubMed: 2837132]
140.
Kanos CC, Davies KG, O’Brien T, DohanJr FC Jr. Hippocampal Sclerosis in a Two-Year-Old with Temporal Lobe Epilepsy: Case Report with Pathological Confirmation. Pediatr Neurosurg. 2000;32:316–20. [PubMed: 10971193]
141.
Babb TL, Brown WJ. Pathological findings in epilepsy. In: Engel J Jr, editor. Surgical treatment of the epilepsies. New York: Raven; 1987. pp. 511–40.
142.
Harvey AS, Grattan-Smith JD, Desmond PM, Chow CW, Berkovic SF. Febrile seizures and hippocampal sclerosis: frequent and related findings in intractable temporal lobe epilepsy of childhood. Pediatr Neurol. 1995;12:201–6. [PubMed: 7619185]
143.
Harvey AS, Berkovic SF, Wrennall JA, Hopkins IJ. Temporal lobe epilepsy in childhood: clinical, EEG, and neuroimaging findings and syndrome classification in a cohort with new-onset seizures. Neurology. 1997;49:960–8. [PubMed: 9339674]
144.
Cendes F, Cook MJ, Watson C, Andermann F, Fish DR, Shorvon SD, et al. Frequency and characteristics of dual pathology in patients with lesional epilepsy. Neurology. 1995;45:2058–64. [PubMed: 7501159]
145.
Falconer MA. Genetic and related aetiological factors in temporal lobe epilepsy. A review. Epilepsia. 1971;12:13–31. [PubMed: 5282880]
146.
Maher J, McLachlan RS. Febrile convulsions. Is seizure duration the most important predictor of temporal lobe epilepsy? Brain. 1995;118:1521–8. [PubMed: 8595481]
147.
Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. Brain. 1995;118:105–18. [PubMed: 7894997]
148.
O’Connor WM, Masukawa L, Freese A, Sperling MR, French JA, O’Connor MJ. Hippocampal cell distributions in temporal lobe epilepsy: a comparison between patients with and without an early risk factor. Epilepsia. 1996;37:440–9. [PubMed: 8617172]
149.
Ohtsu M, Oguni H, Awaya Y, Osawa M. Clinical and EEG analysis of initial status epilepticus during infancy in patients with mesial temporal lobe epilepsy. Brain Dev. 2002;24:231–8. [PubMed: 12015166]
150.
Delgado-Escueta AV, Walsh GO. Type I complex partial seizures of hippocampal origin: excellent results of anterior temporal lobectomy. Neurology. 1985;35:143–54. [PubMed: 3969201]
151.
Dill R, Gullotta F. Pathomorphologic findings in temporal lobe epilepsy. A contribution to the question of ganglioblastomas. Schweiz Arch Neurol Neurochir Psychiatr. 1970;106:241–55. [PubMed: 5458850]
152.
O’Brien TJ, Kilpatrick C, Murrie V, Vogrin S, Morris K, Cook MJ. Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases. Brain. 1996;119:2133–41. [PubMed: 9010016]
153.
Mayanagi Y, Watanabe E, Kaneko Y. Mesial temporal lobe epilepsy: clinical features and seizure mechanism. Epilepsia. 1996;37(Suppl 3):57–60. [PubMed: 8681916]
154.
Szkiladz E, Bacia T, Bidzinski J, Checinski S, Rakowicz M. Somatosensory potentials evoked by stimulation of the median nerves recorded during the operation from the surface of the cerebral cortex in patients with temporal lobe epilepsy. Neurol Neurochir Pol. 1989;23:355–62. [PubMed: 2637967]
155.
Dennis M, Farrell K, Hoffman HJ, Hendrick EB, Becker LE, Murphy EG. Recognition memory of item, associative and serial-order information after temporal lobectomy for seizure disorder. Neuropsychologia. 1988;26:53–65. [PubMed: 3362345]
156.
Jobst BC, Williamson PD, Neuschwander TB, Darcey TM, Thadani VM, Roberts DW. Secondarily generalized seizures in mesial temporal epilepsy: clinical characteristics, lateralizing signs, and association with sleep-wake cycle. Epilepsia. 2001;42:1279–87. [PubMed: 11737163]
157.
Lugaresi E, Pazzaglia P, Tassinari CA. Differentiation of “Absence Status” and “Temporal Lobe Status” Epilepsia. 1971;12:77–87. [PubMed: 4996855]
158.
Shorvon SD. Status epilepticus:its clinical features and treatment in children and adults. Cambridge: Cambridge University Press; 1994.
159.
Burneo JG, Knowlton RC, Gomez C, Martin R, Kuzniecky RI. Confirmation of nonconvulsive limbic status epilepticus with the sodium amytal test. Epilepsia. 2003;44:1122–6. [PubMed: 12887448]
160.
Duncan MB, Maccario M. Transient global amnesia, epilepsy, and migraine: diagnostic comparisons and distinctions. Military Medicine. 1989;154:424–7. [PubMed: 2505176]
161.
Kopelman MD, Panayiotopoulos CP, Lewis P. Transient epileptic amnesia differentiated from psychogenic “fugue”: neuropsychological, EEG, and PET findings. J Neurol Neurosurg Psychiatr. 1994;57:1002–4. [PMC free article: PMC1073093] [PubMed: 8057091]
162.
Licht EA, Fujikawa DG. Nonconvulsive status epilepticus with frontal features: quantitating severity of subclinical epileptiform discharges provides a marker for treatment efficacy, recurrence and outcome. Epilepsy Res. 2002;51:13–21. [PubMed: 12350380]
163.
Thomas P, Zifkin B, Migneco O, Lebrun C, Darcourt J, Andermann F. Nonconvulsive status epilepticus of frontal origin. Neurology. 1999;52:1174–83. [PubMed: 10214739]
164.
Koepp MJ, Richardson MP, Labbe C, Brooks DJ, Cunningham VJ, Ashburner J, et al. 11C-flumazenil PET, volumetric MRI, and quantitative pathology in mesial temporal lobe epilepsy. Neurology. 1997;49:764–73. [PubMed: 9305338]
165.
Kuzniecky R, Bilir E, Gilliam F, Faught E, Martin R, Hugg J. Quantitative MRI in temporal lobe epilepsy: evidence for fornix atrophy. Neurology. 1999;53:496–501. [PubMed: 10449110]
166.
Kuzniecky R, Ho SS, Martin R, Faught E, Morawetz R, Palmer C, et al. Temporal lobe developmental malformations and hippocampal sclerosis: epilepsy surgical outcome. Neurology. 1999;52:479–84. [PubMed: 10025775]
167.
Engel J Jr, Cascino GD, Shields WD. Surgically remediable syndromes. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 1687–96.
168.
Raymond AA, Fish DR, Boyd SG, Smith SJ, Pitt MC, Kendall B. Cortical dysgenesis: serial EEG findings in children and adults. Electroencephalogr Clin Neurophysiol. 1995;94:389–97. [PubMed: 7607092]
169.
Falconer MA. Discussion on the surgery of temporal lobe epilepsy:syrgical and pathologica aspects. Proc Royal Soc Medicine. 1953;44:971–5.
170.
Falconer MA. Mesial temporal (Ammon’s horn) sclerosis as a common cause of epilepsy. Aetiology, treatment, and prevention. Lancet. 1974;2:767–70. [PubMed: 4143026]
171.
Loiseau P, Beaussart M. Hereditary factors in partial epilepsy. Epilepsia. 1969;10:23–31. [PubMed: 4976748]
172.
Berkovic SF, Jackson GD. The hippocampal sclerosis whodunit: enter the genes [editorial] Ann Neurol. 2000;47:557–8. [PubMed: 10805324]
173.
Kobayashi E, Lopes-Cendes I, Guerreiro CA, Sousa SC, Guerreiro MM, Cendes F. Seizure outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy. Neurology. 2001;56:166–72. [PubMed: 11160950]
174.
Kobayashi E, Li LM, Lopes-Cendes I, Cendes F. Magnetic resonance imaging evidence of hippocampal sclerosis in asymptomatic, first-degree relatives of patients with familial mesial temporal lobe epilepsy. Arch Neurol. 2002;59:1891–4. [PubMed: 12470176]
175.
Proper EA, Oestreicher AB, Jansen GH, Veelen CW, van Rijen PC, Gispen WH, et al. Immunohistochemical characterization of mossy fibre sprouting in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Brain. 2000;123:19–30. [PubMed: 10611117]
176.
Sutula T, Cascino G, Cavazos J, Parada I, Ramirez L. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol. 1989;26:321–30. [PubMed: 2508534]
177.
de Lanerolle NC, Kim JH, Robbins RJ, Spencer DD. Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res. 1989;495:387–95. [PubMed: 2569920]
178.
Jefferys JG. Hippocampal sclerosis and temporal lobe epilepsy: cause or consequence? [editorial] Brain. 1999;122:1007–8. [PubMed: 10356054]
179.
Scott RC. Childhood status epilepticus:structural consequences and assessment of a novel treatment. Institute of child health. University College London Medical School; 1999. PhD Thesis.
180.
VanLandingham KE, Heinz ER, Cavazos JE, Lewis DV. Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions. Ann Neurol. 1998;43:413–26. [PubMed: 9546321]
181.
Fernandez G, Effenberger O, Vinz B, Steinlein O, Elger CE, Dohring W, et al. Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology. 1998;50:909–17. [PubMed: 9566371]
182.
Berg AT, Shinnar S, Levy SR, Testa FM. Childhood-onset epilepsy with and without preceding febrile seizures. Neurology. 1999;53:1742–8. [PubMed: 10563622]
183.
Brines ML, Sundaresan S, Spencer DD, de Lanerolle NC. Quantitative autoradiographic analysis of ionotropic glutamate receptor subtypes in human temporal lobe epilepsy: up-regulation in reorganized epileptogenic hippocampus. Eur J Neurosci. 1997;9:2035–44. [PubMed: 9421164]
184.
Engel J Jr, Wilson C, Bragin A. Advances in understanding the process of epileptogenesis based on patient material: what can the patient tell us? Epilepsia. 2003;44(Suppl 12):60–71. [PubMed: 14641562]
185.
Bragin A, Engel J Jr, Wilson CL, Fried I, Mathern GW. Hippocampal and entorhinal cortex high-frequency oscillations (100—500 Hz) in human epileptic brain and in kainic acid—treated rats with chronic seizures. Epilepsia. 1999;40:127–37. [PubMed: 9952257]
186.
Stoffel-Wagner B, Beyenburg S, Watzka M, Blumcke I, Bauer J, Schramm J, et al. Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy. Epilepsia. 2000;41:140–7. [PubMed: 10691110]
187.
Suckling J, Roberts H, Walker M, Highley JR, Fenwick P, Oxbury J, et al. Temporal lobe epilepsy with and without psychosis: exploration of hippocampal pathology including that in subpopulations of neurons defined by their content of immunoreactive calcium-binding proteins. Acta Neuropathol. (Berl) 2000;99:547–54. [PubMed: 10805100]
188.
Hinterkeuser S, Schroder W, Hager G, Seifert G, Blumcke I, Elger CE, et al. Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. Eur J Neurosci. 2000;12:2087–96. [PubMed: 10886348]
189.
Kashihara K, Akiyama K, Kodama M, Kohira I, Abe K. Temporal changes in expression of neuronal nitric oxide synthase mRNA in the rat hippocampus associated with kainate-induced seizures. Neurol Res. 2000;22:409–12. [PubMed: 10874692]
190.
Nagerl UV, Mody I, Jeub M, Lie AA, Elger CE, Beck H. Surviving granule cells of the sclerotic human hippocampus have reduced Ca(2+) influx because of a loss of calbindin-D(28k) in temporal lobe epilepsy. J Neurosci. 2000;20:1831–6. [PubMed: 10684884]
191.
Cavazos JE, Jones SM, Cross DJ. Sprouting and synaptic reorganization in the subiculum and CA1 region of the hippocampus in acute and chronic models of partial-onset epilepsy. Neuroscience. 2004;126:677–88. [PMC free article: PMC3179906] [PubMed: 15183517]
192.
Moser DJ, Bauer RM, Gilmore RL, Dede DE, Fennell EB, Algina JJ, et al. Electroencephalographic, volumetric, and neuropsychological indicators of seizure focus lateralization in temporal lobe epilepsy. Arch Neurol. 2000;57:707–12. [PubMed: 10815137]
193.
Cendes F, Li LM, Watson C, Andermann F, Dubeau F, Arnold DL. Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide. Arch Neurol. 2000;57:497–500. [PubMed: 10768623]
194.
Kuzniecky RI, Jackson GD. Magnetic resonance in epilepsy. New York: Raven Press; 1995.
195.
Ho SS, Kuzniecky RI, Gilliam F, Faught E, Bebin M, Morawetz R. Congenital porencephaly and hippocampal sclerosis. Clinical features and epileptic spectrum. Neurology. 1997;49:1382–8. [PubMed: 9371926]
196.
Henry TR, Mazziotta JC, Engel J Jr, Christenson PD, Zhang JX, Phelps ME, et al. Quantifying interictal metabolic activity in human temporal lobe epilepsy. J Cereb Blood Flow Metab. 1990;10:748–57. [PubMed: 2384546]
197.
Hajek M, Antonini A, Leenders KL, Wieser HG. Mesiobasal versus lateral temporal lobe epilepsy: metabolic differences in the temporal lobe shown by interictal 18F-FDG positron emission tomography. Neurology. 1993;43:79–86. [PubMed: 8423915]
198.
Koutroumanidis M, Hennessy MJ, Seed PT, Elwes RD, Jarosz J, Morris RG, et al. Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy. Neurology. 2000;54:1811–21. [PubMed: 10802790]
199.
Lamusuo S, Pitkanen A, Jutila L, Ylinen A, Partanen K, Kalviainen R, et al. [11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology. Neurology. 2000;54:2252–60. [PubMed: 10881249]
200.
Koepp MJ, Hammers A, Labbe C, Woermann FG, Brooks DJ, Duncan JS. 11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI. Neurology. 2000;54:332–9. [PubMed: 10668692]
201.
Ho SS, Berkovic SF, McKay WJ, Kalnins RM, Bladin PF. Temporal lobe epilepsy subtypes: differential patterns of cerebral perfusion on ictal SPECT. Epilepsia. 1996;37:788–95. [PubMed: 8764820]
202.
Meiners LC, van der GJ, van Rijen PC, Springorum R, de Kort GA, Jansen GH. Proton magnetic resonance spectroscopy of temporal lobe white matter in patients with histologically proven hippocampal sclerosis. J Magn Reson Imaging. 2000;11:25–31. [PubMed: 10676617]
203.
Chu WJ, Kuzniecky RI, Hugg JW, Abou-Khalil B, Gilliam F, Faught E, et al. Statistically driven identification of focal metabolic abnormalities in temporal lobe epilepsy with corrections for tissue heterogeneity using 1H spectroscopic imaging. Magn Reson Med. 2000;43:359–67. [PubMed: 10725878]
204.
Hetherington H, Kuzniecky R, Pan J, Mason G, Morawetz R, Harris C, et al. Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T. Ann Neurol. 1995;38:396–404. [PubMed: 7668825]
205.
Kuzniecky R, Hugg JW, Hetherington H, Butterworth E, Bilir E, Faught E, et al. Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy. Neurology. 1998;51:66–71. [PubMed: 9674780]
206.
Namer IJ, Bolo NR, Sellal F, Nguyen VH, Nedelec JF, Hirsch E, et al. Combined measurements of hippocampal N-acetyl-aspartate and T2 relaxation time in the evaluation of mesial temporal lobe epilepsy: correlation with clinical severity and memory performances. Epilepsia. 1999;40:1424–32. [PubMed: 10528939]
207.
Capizzano AA, Vermathen P, Laxer KD, Matson GB, Maudsley AA, Soher BJ, et al. Multisection proton MR spectroscopy for mesial temporal lobe epilepsy. Am J Neuroradiol. 2002;23:1359–68. [PMC free article: PMC2753243] [PubMed: 12223379]
208.
Li LM, Cendes F, Antel SB, Andermann F, Serles W, Dubeau F, et al. Prognostic value of proton magnetic resonance spectroscopic imaging for surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy. Ann Neurol. 2000;47:195–200. [PubMed: 10665490]
209.
Chu WJ, Hetherington HP, Kuzniecky RI, Simor T, Mason GF, Elgavish GA. Lateralization of human temporal lobe epilepsy by 31P NMR spectroscopic imaging at 4.1 T. Neurology. 1998;51:472–9. [PubMed: 9710021]
210.
Williamson PD, French JA, Thadani VM, Kim JH, Novelly RA, Spencer SS, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol. 1993;34:781–7. [PubMed: 8250526]
211.
Sadler RM, Blume WT. Significance of bisynchronous spike-waves in patients with temporal lobe spikes. Epilepsia. 1989;30:143–6. [PubMed: 2494040]
212.
Spencer SS, McCarthy G, Spencer DD. Diagnosis of medial temporal lobe seizure onset: relative specificity and sensitivity of quantitative MRI. Neurology. 1993;43:2117–24. [PubMed: 8413976]
213.
Le Van QM, Adam C, Martinerie J, Baulac M, Clemenceau S, Varela F. Spatio-temporal characterizations of non-linear changes in intracranial activities prior to human temporal lobe seizures. Eur J Neurosci. 2000;12:2124–34. [PubMed: 10886352]
214.
Baumgartner C, Pataraia E, Lindinger G, Deecke L. Neuromagnetic recordings in temporal lobe epilepsy. J Clin Neurophysiol. 2000;17:177–89. [PubMed: 10831109]
215.
Meyer MA, Zimmerman AW, Miller CA. Temporal lobe epilepsy presenting as panic attacks: detection of interictal hypometabolism with positron emission tomography. J Neuroimaging. 2000;10:120–2. [PubMed: 10800267]
216.
Lin YY, Su MS, Yiu CH, Shih YH, Yen DJ, Kwan SY, et al. Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy. Neurology. 1997;49:528–32. [PubMed: 9270590]
217.
Trenerry MR, Jack CR Jr, Sharbrough FW, Cascino GD, Hirschorn KA, Marsh WR, et al. Quantitative MRI hippocampal volumes: association with onset and duration of epilepsy, and febrile convulsions in temporal lobectomy patients. Epilepsy Res. 1993;15:247–52. [PubMed: 8223421]
218.
Miller SP, Li LM, Cendes F, Caramanos Z, Rosenblatt B, Shevell MI, et al. Neuronal dysfunction in children with newly diagnosed temporal lobe epilepsy. Pediatr Neurol. 2000;22:281–6. [PubMed: 10788744]
219.
Engel J Jr. Introduction to temporal lobe epilepsy. Epilepsy Res. 1996;26:141–50. [PubMed: 8985696]
220.
Engel J Jr. Clinical evidence for the progressive nature of epilepsy. Epilepsy Res Suppl. 1996;12:9–20. [PubMed: 9302499]
221.
Blume WT, Hwang PA. Pediatric candidates for temporal lobe epilepsy surgery. Can J Neurol Sci. 2000;27(Suppl 1):S14–S19. [PubMed: 10830322]
222.
Polkey CE. Temporal lobe resections. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 667–95.
223.
Engel J Jr. The timing of surgical intervention for mesial temporal lobe epilepsy: a plan for a randomized clinical trial. Arch Neurol. 1999;56:1338–41. [PubMed: 10555652]
224.
Polkey CE. Surgical treatment of epilepsy. Lancet. 1990;336:553–5. [PubMed: 1975049]
225.
Hennessy MJ, Elwes RD, Rabe-Hesketh S, Binnie CD, Polkey CE. Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis. Acta Neurol Scand. 2001;103:344–50. [PubMed: 11421846]
226.
Hennessy MJ, Langan Y, Elwes RD, Binnie CD, Polkey CE, Nashef L. A study of mortality after temporal lobe epilepsy surgery. Neurology. 1999;53:1276–83. [PubMed: 10522885]
227.
McKhann GM, Schoenfeld-McNeill J, Born DE, Haglund MM, Ojemann GA. Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. J Neurosurg. 2000;93:44–52. [PubMed: 10883904]
228.
Mizrahi EM, Kellaway P, Grossman RG, Rutecki PA, Armstrong D, Rettig G, et al. Anterior temporal lobectomy and medically refractory temporal lobe epilepsy of childhood. Epilepsia. 1990;31:302–12. [PubMed: 2344847]
229.
Falconer MA. Discussion on the surgery of temporal lobe epilepsy:surgical and pathological aspects. Proc Royal Soc Medicine. 1953;44:971–5.
230.
Salanova V, Morris HH, Van Ness P, Kotagal P, Wyllie E, Luders H. Frontal lobe seizures: electroclinical syndromes. Epilepsia. 1995;36:16–24. [PubMed: 8001503]
231.
Chauvel P, Delgado-Escueta AV, Halgren E, Bancaud J. Frontal lobe seizures and epilepsies. Adv Neurol. 1992:1–750.
232.
Bancaud J, Talairach J. Clinical semiology of frontal lobe seizures. Adv Neurol. 1992;57:3–58. [PubMed: 1543059]
233.
Jasper H, Riggio S, Goldman-Rakie P. Epilepsy and the functional anatomy of the frontal lobe. New York: Raven Press; 1995.
234.
Chauvel P, Kliemann F, Vignal JP, Chodkiewicz JP, Talairach J, Bancaud J. The clinical signs and symptoms of frontal lobe seizures. Phenomenology and classification. Adv Neurol. 1995;66:115–25. [PubMed: 7771296]
235.
Williamson PD. Frontal lobe epilepsy. Some clinical characteristics. Adv Neurol. 1995;66:127–50. [PubMed: 7771297]
236.
Kotagal P, Arunkumar GS. Lateral frontal lobe seizures. Epilepsia. 1998;39(Suppl 4):S62–S68. [PubMed: 9637594]
237.
Niedermeyer E. Frontal lobe epilepsy: the next frontier. Clin Electroencephalogr. 1998;29:163–9. [PubMed: 9783089]
238.
Bartolomei F, Chauvel P. Seizure symptoms and cerebral localization:frontal lobe and rolandic seizures. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000. pp. 55–62.
239.
Blume WT, Ociepa D, Kander V. Frontal lobe seizure propagation: scalp and subdural EEG studies. Epilepsia. 2001;42:491–503. [PubMed: 11440344]
240.
Sinclair DB, Wheatley M, Snyder T. Frontal lobe epilepsy in childhood. Pediatr Neurol. 2004;30:169–76. [PubMed: 15033198]
241.
Goldman-Rakie P. Anatomical and functional circuits in prefrontal cortex of non-human primates. Relevance to epilepsy. Adv Neurol. 1995;66:51–65. [PubMed: 7771311]
242.
Rasmussen T. Characteristics of a pure culture of frontal lobe epilepsy. Epilepsia. 1983;24:482–93. [PubMed: 6873005]
243.
Manford M, Hart YM, Sander JW, Shorvon SD. National General Practice Study of Epilepsy (NGPSE): partial seizure patterns in a general population. Neurology. 1992;42:1911–7. [PubMed: 1407572]
244.
Laich E, Kuzniecky R, Mountz J, Liu HG, Gilliam F, Bebin M, et al. Supplementary sensorimotor area epilepsy. Seizure localization, cortical propagation and subcortical activation pathways using ictal SPECT. Brain. 1997;120:855–64. [PubMed: 9183255]
245.
Baumgartner C, Flint R, Tuxhorn I, Van Ness PC, Kosalko J, Olbrich A, et al. Supplementary motor area seizures: propagation pathways as studied with invasive recordings. Neurology. 1996;46:508–14. [PubMed: 8614523]
246.
King DW, Smith JR. Supplementary sensorimotor area epilepsy in adults. Adv Neurol. 1996;70:285–91. [PubMed: 8615209]
247.
Spencer DD, Schumacher J. Surgical management of patients with intractable supplementary motor area seizures. The Yale experience. Adv Neurol. 1996;70:445–50. [PubMed: 8615223]
248.
Connolly MB, Langill L, Wong PK, Farrell K. Seizures involving the supplementary sensorimotor area in children: a video-EEG analysis. Epilepsia. 1995;36:1025–32. [PubMed: 7555953]
249.
So NK. Supplementary motor area epilepsy:the clinical syndrome. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey & Company Ltd; 1994. pp. 299–317.
250.
Holthausen H, Hoppe M. Hypermotor seizures. In: Luders HO, Noachtar S, editors. Epileptic seizures. Pathophysiology and clinical semiology. New York: Churchill Livingstone; 2000. pp. 439–48.
251.
Penfield W. The supplementary motor area in the cerebral cortex of man. Arch Psychiatr. 1950;185:670–4. [PubMed: 14800366]
252.
Luders HO, Noachtar S, Burgess RC. Semiologic classification of epileptic seizures. In: Luders HO, Noachtar S, editors. Epileptic seizures. Pathophysiology and clinical semiology. New York: Churchill Livingstone; 2000. pp. 263–85.
253.
Marchesi GF, Macchi G, Cianchetti C, Chinzari P. Supplementary motor areas in the cat: electrophysiological studies of the suprasylvian and ectosylvian regions. Boll Soc Ital Biol Sper. 1972;48:70–4. [PubMed: 5032469]
254.
Van Ness PC, Bleasel A, Tuxhorn I. Supplementary motor seizures: localization of the epileptogenic zone. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey & Company Ltd; 1994. pp. 319–30.
255.
Bancaud J. Kojewnikow’s syndrome (epilepsia partialis continua) in children. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 1992. pp. 363–74.
256.
Foerster O, Penfield W. The structural basis of traumatic epilepsy and results of radical operation. Assoc Res Nev Ment Dis. 1929;7:569–91.
257.
Gastaut H, Jasper H, Bancaud J, Waltregny A, editors. The physiopathogenesis of the epilepsies. Springfield, Illinois: Charles C Thomas; 1969.
258.
Bancaud J. Physiopathogenesis of generalised epilepsies of organic nature (stereo-electroencephalographic study) In: Gastaut H, Jasper H, Bancaud J, Waltregny A, editors. The physiopathogenesis of the epilepsies. Springfield: Charles C Thomas; 1969. pp. 158–85.
259.
Quesney LF, Constain M, Rasmussen T. Seizures from the dorsolateral frontal lobe. Adv Neurol. 1992;57:233–43. [PubMed: 1543054]
260.
Geier S, Bancaud J, Talairach J, Bonis A, Szikla G, Enjelvin M. The seizures of frontal lobe epilepsy. A study of clinical manifestations. Neurology. 1977;27:951–8. [PubMed: 561909]
261.
Chauvel P, Bancaud J. The spectrum of frontal lobe seizures:with a note of frontal lobe syndromatology. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey & Company Ltd; 1994. pp. 331–4.
262.
Sartori E, Biraben A, Taussig D, Bernard AM, Scarabin JM. Gelastic seizures: video-EEG and scintigraphic analysis of a case with a frontal focus; review of the literature and pathophysiological hypotheses. Epilep Disord. 1999;1:221–8. [PubMed: 10937157]
263.
Janszky J, Jokeit H, Schulz R, Hoppe M, Ebner A. EEG predicts surgical outcome in lesional frontal lobe epilepsy. Neurology. 2000;54:1470–6. [PubMed: 10751260]
264.
Genow A, Hummel C, Scheler G, Hopfengartner R, Kaltenhauser M, Buchfelder M, et al. Epilepsy surgery, resection volume and MSI localization in lesional frontal lobe epilepsy. Neuroimage. 2004;21:444–9. [PubMed: 14741681]
265.
Engel J Jr, Henry TR, Swartz BE. Positron emission tomography in frontal lobe epilepsy. Adv. Neurol. 1995;66:223–38. [PubMed: 7771304]
266.
Czapinski P, Terczynski A. Intravenous valproic acid administration in status epilepticus. Neurol Neurochir Pol. 1998;32:11–22. [PubMed: 9631374]
267.
Hopkins H. The time of appearance of epileptic seizures in relation to age, duration and type of the syndrome. J Nerv Ment Dis. 1933;77:153–62.
268.
Ferri R, Stam CJ, Lanuzza B, Cosentino FI, Elia M, Musumeci SA, et al. Different EEG frequency band synchronization during nocturnal frontal lobe seizures. Clin Neurophysiol. 2004;115:1202–11. [PubMed: 15066546]
269.
Allen PJ, Fish DR, Smith SJ. Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy. Electroencephalogr Clin Neurophysiol. 1992;82:155–9. [PubMed: 1370786]
270.
Bautista RE, Spencer DD, Spencer SS. EEG findings in frontal lobe epilepsies. Neurology. 1998;50:1765–71. [PubMed: 9633725]
271.
Williamson A, Spencer SS, Spencer DD. Depth electrode studies and intracellular dentate granule cell recordings in temporal lobe epilepsy. Ann Neurol. 1995;38:778–87. [PubMed: 7486870]
272.
Fahn S. The early history of paroxysmal dyskinesias. Adv Neurol. 2002;89:377–85. [PubMed: 11968462]
273.
Jankovic J, Demirkiran M. Classification of paroxysmal dyskinesias and ataxias. Adv Neurol. 2002;89:387–400. [PubMed: 11968463]
274.
Guerrini R. Idiopathic epilepsy and paroxysmal dyskinesia. Epilepsia. 2001;42(Suppl 3):36–41. [PubMed: 11520321]
275.
LeWitt PA. Psychogenic movement disorders. In: Gilman S, editor. Neurobase. San Diego SA: Arbor Publishing Corp; 2000.
276.
Matsuo H, Kamakura K, Matsushita S, Ohmori T, Okano M, Tadano Y, et al. Mutational analysis of the anion exchanger 3 gene in familial paroxysmal dystonic choreoathetosis linked to chromosome 2q. Am J Med Genet. 1999;88:733–7. [PubMed: 10581498]
277.
Houser MK, Soland VL, Bhatia KP, Quinn NP, Marsden CD. Paroxysmal kinesigenic choreoathetosis: a report of 26 patients. J Neurol. 1999;246:120–6. [PubMed: 10195407]
278.
Sadamatsu M, Masui A, Sakai T, Kunugi H, Nanko S, Kato N. Familial paroxysmal kinesigenic choreoathetosis: an electrophysiologic and genotypic analysis. Epilepsia. 1999;40:942–9. [PubMed: 10403218]
279.
Tomita H, Nagamitsu S, Wakui K, Fukushima Y, Yamada K, Sadamatsu M, et al. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2– q12.1. Am J Hum Genet. 1999;65:1688–97. [PMC free article: PMC1288380] [PubMed: 10577923]
280.
Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, et al. Coding and noncoding variation of the human calcium-channel beta4- subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am. J Hum Genet. 2000;66:1531–9. [PMC free article: PMC1378014] [PubMed: 10762541]
281.
Boland LM, Price DL, Jackson KA. Episodic ataxia/myokymia mutations functionally expressed in the Shaker potassium channel. Neuroscience. 1999;91:1557–64. [PubMed: 10391459]
282.
Denier C, Ducros A, Vahedi K, Joutel A, Thierry P, Ritz A, et al. High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2. Neurology. 1999;52:1816–21. [PubMed: 10371528]
283.
Zuberi SM, Eunson LH, Spauschus A, De Silva R, Tolmie J, Wood NW, et al. A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy. Brain. 1999;122:817–25. [PubMed: 10355668]
284.
Lance JW. Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Ann Neurol. 1977;2:285–93. [PubMed: 617268]
285.
Hayashi R, Hanyu N, Yahikozawa H, Yanagisawa N. Ictal muscle discharge pattern and SPECT in paroxysmal kinesigenic choreoathetosis. Electromyogr Clin Neurophysiol. 1997;37:89–94. [PubMed: 9098672]
286.
Wein T, Andermann F, Silver K, Dubeau F, Andermann E, Rourke-Frew F, et al. Exquisite sensitivity of paroxysmal kinesigenic choreoathetosis to carbamazepine. Neurology. 1996;47:1104–6. [PubMed: 8857757]
287.
Hamada Y, Hattori H, Okuno T. Eleven cases of paroxysmal kinesigenic choreoathetosis; correlation with benign infantile convulsions. No To Hattatsu. 1998;30:483–8. [PubMed: 9844411]
288.
Ferrie CD, Giannakodimos S, Robinson RO, Panayiotopoulos CP. Symptomatic typical absence seizures. In: Duncan JS, Panayiotopoulos CP, editors. Typical absences and related epileptic syndromes. London: Churchill Communications Europe; 1995. pp. 241–52.
289.
Kudo T, Sato K, Yagi K, Seino M. Can absence status epilepticus be of frontal lobe origin? Act Neurol Scand. 1995;92:472–7. [PubMed: 8750113]
290.
Pavone A, Niedermeyer E. Absence seizures and the frontal lobe. Clin Electroencephalogr. 2000;31:153–6. [PubMed: 10923203]
291.
Olivier A. Surgery of frontal lobe epilepsy. Adv Neurol. 1995;66:321–48. [PubMed: 7771309]
292.
Obeso JA, Rothwell JC, Marsden CD. The spectrum of cortical myoclonus. From focal reflex jerks to spontaneous motor epilepsy. Brain. 1985;108:193–24. [PubMed: 3919883]
293.
Bancauc J. Kojewnikow’s syndrome (epilepsia partialis continua) in children: Up-date. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 1992. pp. 374–9.
294.
Schomer DL. Focal status epilepticus and epilepsia partialis continua in adults and children. Epilepsia. 1993;34(Suppl 1):S29–36. [PubMed: 7681771]
295.
Cockerell OC, Rothwell J, Thompson PD, Marsden CD, Shorvon SD. Clinical and physiological features of epilepsia partialis continua. Cases ascertained in the UK. Brain. 1996;119:393–407. [PubMed: 8800935]
296.
Biraben A, Chauvel P. Epilepsia Partialis Continua. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 2447–53.
297.
Shigeto H, Tobimatsu S, Morioka T, Yamamoto T, Kobayashi T, Kato M. Jerk-locked back averaging and dipole source localization of magnetoencephalographic transients in a patient with epilepsia partialis continua. Electroencephalogr Clin Neurophysiol. 1997;103:440–4. [PubMed: 9368488]
298.
Molyneux PD, Barker RA, Thom M, van Paesschen W, Harkness WF, Duncan JS. Successful treatment of intractable epilepsia partialis continua with multiple subpial transections. J Neurol Neurosurg Psychiatry. 1998;65:137–8. [PMC free article: PMC2170173] [PubMed: 9667583]
299.
Wieser HG. Epilepsia partialis continua. In: Gilman S, editor. Medlink. San Diego SA: Arbor Publishing Corp; 2004.
300.
Caraballo R, Tenembaum S, Cersosimo R, Pomata H, Medina C, Soprano AM, et al. Rasmussen syndrome. Rev Neurol. 1998;26:978–83. [PubMed: 9658472]
301.
Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua. A review of 32 cases. Arch Neurol. 1977;34:266–75. [PubMed: 404996]
302.
Rosenbaum DH, Rowan AJ. Unilateral truncal seizures: frontal origin. Epilepsia. 1990;31:37–40. [PubMed: 2137408]
303.
Silver K, Andermann F, Meagher-Villemure K. Familial alternating epilepsia partialis continua with chronic encephalitis: another variant of Rasmussen syndrome? Arch Neurol. 1998;55:733–6. [PubMed: 9605733]
304.
Wieser HG, Graf HP, Bernoulli C, Siegfried J. Quantitative analysis of intracerebral recordings in epilepsia partialis continua. Electroencephalogr Clin Neurophysiol. 1978;44:14–22. [PubMed: 74322]
305.
Perniola T, Sforza E, Rodriguez M, Margari L. Neurophysiological follow-up in a case of chronic progressive epilepsia partialis continua of childhood. Ital J Neurol Sci. 1989;10:369–76. [PubMed: 2767945]
306.
Velasco M, Velasco F, Alcala H, Diaz de Leon AE. Wakefulness-sleep modulation of EEG-EMG epileptiform activities: a quantitative study on a child with intractable epilepsia partialis continua. Int J Neurosci. 1990;54:325–37. [PubMed: 2125031]
307.
Ambrosetto C, Lugaresi E, Tassinari CA. The evolution of physiological sleep in states of epilepsia partialis continuans. Electroencephalogr Clin Neurophysiol. 1967;23:186–7. [PubMed: 4166719]
308.
Dereux J. Le syndrome de Kojewnikow (epilepsie partialis continue) Paris: Thesis; 1955.
309.
Andermann F, Hart Y. Rasmussen’s syndrome. In: Gilman S, editor. Medlink Neurology. San Diego SA: 2004.
310.
Panayiotopoulos CP, Andermann F. Kozhevnikov-Rasmussen syndrome and the new proposal on classification. Epilepsia. 2002;43:948–50. [PubMed: 12181019]
311.
Adams RD, Victor M, Ropper AH. Principles of Neurology. New York: McGraw-Hill; 1997.
312.
Rasmussen T. Surgery for central, parietal and occipital epilepsy. Can J Neurol Sci. 1991;18:611–6. [PubMed: 1777881]
313.
Williamson PD, Boon PA, Thadani VM, Darcey TM, Spencer DD, Spencer SS, et al. Parietal lobe epilepsy: diagnostic considerations and results of surgery. Ann Neurol. 1992;31:193–201. [PubMed: 1575458]
314.
Cascino GD, Hulihan JF, Sharbrough FW, Kelly PJ. Parietal lobe lesional epilepsy: electroclinical correlation and operative outcome. Epilepsia. 1993;34:522–7. [PubMed: 8504784]
315.
Sveinbjornsdottir S, Duncan JS. Parietal and occipital lobe epilepsy: a review. Epilepsia. 1993;34:493–521. [PubMed: 8504783]
316.
Ho SS, Berkovic SF, Newton MR, Austin MC, McKay WJ, Bladin PF. Parietal lobe epilepsy: clinical features and seizure localization by ictal SPECT. Neurology. 1994;44:2277–84. [PubMed: 7991112]
317.
Williamson PD. Seizures with origin in the occipital or parietal lobes. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey & Company Ltd; 1994. pp. 383–90.
318.
Salanova V, Andermann F, Rasmussen T, Olivier A, Quesney LF. Parietal lobe epilepsy. Clinical manifestations and outcome in 82 patients treated surgically between 1929 and 1988. Brain. 1995;118:607–27. [PubMed: 7600082]
319.
Salanova V, Andermann F, Rasmussen T, Olivier A, Quesney LF. Tumoural parietal lobe epilepsy. Clinical manifestations and outcome in 34 patients treated between 1934 and 1988. Brain. 1995;118:1289–304. [PubMed: 7496787]
320.
Abou-Khalil B, Fakhoury T, Jennings M, Moots P, Warner J, Kessler RM. Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities. Act Neurol Scand. 1995;91:103–8. [PubMed: 7785419]
321.
Olivier A, Boling W Jr. Surgery of parietal and occipital lobe epilepsy. Adv. Neurol. 2000;84:533–75. [PubMed: 11091895]
322.
Siegel AM, Williamson PD. Parietal lobe epilepsy. Adv Neurol. 2000;84:189–99. [PubMed: 11091867]
323.
Kasowski HJ, Stoffman MR, Spencer SS, Spencer DD. Surgical management of parietal lobe epilepsy. Adv Neurol. 2003;93:347–56. [PubMed: 12894419]
324.
Kim DW, Lee SK, Yun CH, Kim KK, Lee DS, Chung CK, et al. Parietal lobe epilepsy: the semiology, yield of diagnostic workup, and surgical outcome. Epilepsia. 2004;45:641–9. [PubMed: 15144429]
325.
Rasmussen T. Surgery for epilepsy arising in regions other than the temporal and frontal lobes. Adv Neurol. 1975;8:207–26. [PubMed: 1119355]
326.
Tuxhorn I, Kerdar MS. Somatosensory auras. In: Luders HO, Noachtar S, editors. Epileptic seizures. Pathophysiology and clinical semiology. New York: Churchill Livingstone; 2000. pp. 286–97.
327.
Siegel AM, Williamson PD, Roberts DW, Thadani VM, Darcey TM. Localized pain associated with seizures originating in the parietal lobe. Epilepsia. 1999;40:845–55. [PubMed: 10403207]
328.
Panayiotopoulos CP. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999.
329.
Blume WT, Jones DC, Young GB, Girvin JP, McLachlan RS. Seizures involving secondary sensory and related areas. Brain. 1992;115:1509–20. [PubMed: 1422801]
330.
Stoffels C, Munari C, Bonis A, Bancaud J, Talairach J. Genital and sexual manifestations occurring in the course of partial seizures in man. Rev Electroencephalogr Neurophysiol Clin. 1980;10:386–92. [PubMed: 6795697]
331.
Calleja J, Carpizo R, Berciano J. Orgasmic epilepsy. Epilepsia. 1988;29:635–9. [PubMed: 3409850]
332.
Grand’Maison F, Reiher J, Lebel ML, Rivest J. Transient anosognosia for episodic hemiparesis: a singular manifestation of TIAs and epileptic seizures. Can J Neurol Sci. 1989;16:203–5. [PubMed: 2731090]
333.
Heilman KM, Howell GJ. Seizure-induced neglect. J Neurol Neurosurg Psychiatry. 1980;43:1035–40. [PMC free article: PMC490757] [PubMed: 6777464]
334.
Schwartz TH, Resor SR Jr, De La PR, Goodman RR. Functional magnetic resonance imaging localization of ictal onset to a dysplastic cleft with simultaneous sensorimotor mapping: intraoperative electrophysiological confirmation and postoperative follow-up: technical note. Neurosurgery. 1998;43:639–44. [PubMed: 9733324]
335.
Russell WR, Whitty CWM. Studies in traumatic epilepsy. 2. Focal motor and somatic sensory fits: A study of 85 cases. J Neurol Neurosurg Psychiatr. 1953;16:73–97. [PMC free article: PMC503119] [PubMed: 13053229]
336.
Mauguiere F, Courjon J. Somatosensory epilepsy. A review of 127 cases. Brain. 1978;101:307–32. [PubMed: 96911]
337.
Fish DR, Gloor P, Quesney FL, Olivier A. Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Pathophysiological implications. Brain. 1993;116:397–414. [PubMed: 8461973]
338.
Palmini A, Gloor P. The localizing value of auras in partial seizures: a prospective and retrospective study. Neurology. 1992;42:801–8. [PubMed: 1565234]
339.
Penfield W, Boldrey E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain. 1937;60:389–443.
340.
Fujino O, Hashimoto K, Enokido H, Komatsuzaki H, Fujita T, Takaishi Y, et al. Epileptic vertiginous seizure in a Japanese boy: a case report. No To Hattatsu. 1996;28:515–9. [PubMed: 8940879]
341.
Kogeorgos J, Scott DF, Swash M. Epileptic dizziness. B Med J. 1981;282:687–9. [PMC free article: PMC1504534] [PubMed: 6781616]
342.
Lesser RP, Lueders H, Conomy JP, Furlan AJ, Dinner DS. Sensory seizure mimicking a psychogenic seizure. Neurology. 1983;33:800–2. [PubMed: 6682528]
343.
Foerster O. The cerebral cortex in man. Lancet. 1931;2:309–12.
344.
Penfield W, Gage L. Cerebral localization of epileptic manifestations. Arch Neurol Psychiatry. 1933;30:709–27.
345.
Vignal JP, Biraben A, Chauvel PY, Reutens DC. Reflex partial seizures of sensorimotor cortex (including cortical reflex myoclonus and startle epilepsy) Adv Neurol. 1998;75:207–26. [PubMed: 9385423]
346.
Van Ness PC, Lesser RP, Duchowny MS. Simple sensory seizures. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive textbook. 1997. pp. 533–42.
347.
Reder AT, Wright FS. Epilepsy evoked by eating: the role of peripheral input. Neurology. 1982;32:1065–9. [PubMed: 7202162]
348.
Sutherling WW, Hershman LM, Miller JQ, Lee SI. Seizures induced by playing music. Neurology. 1980;30:1001–4. [PubMed: 6775246]
349.
Koutroumanidis M, Pearce R, Sadoh DR, Panayiotopoulos CP. Tooth brushing-induced seizures: a case report. Epilepsia. 2001;42:686–8. [PubMed: 11380579]
350.
Devinsky O, Kelley K, Porter RJ, Theodore WH. Clinical and electroencephalographic features of simple partial seizures. Neurology. 1988;38:1347–52. [PubMed: 3137487]
351.
Kaibara M, Blume WT. The postictal electroencephalogram. Electroencephalogr Clin Neurophysiol. 1988;70:99–104. [PubMed: 2456198]
352.
Poeck K. Differential diagnosis of “migraine accompagnee” and sensory Jacksonian seizures. Dtsch Med Wochenschr. 1972;97:637–41. [PubMed: 4623371]
353.
Andermann F, Beaumanoir A, Mira E, Roger J, Tassinari CA, editors. Occipital seizures and epilepsies in children. London: John Libbey & Company Ltd; 1993.
354.
Salanova V, Andermann F, Rasmussen TB. Occipital lobe epilesy. In: Wyllie E, editor. The treatment of epilepsy. Philadelphia: Lee & Febiger; 1993. pp. 533–40.
355.
Kuzniecky R, Gilliam F, Morawetz R, Faught E, Palmer C, Black L. Occipital lobe developmental malformations and epilepsy: clinical spectrum, treatment, and outcome. Epilepsia. 1997;38:175–81. [PubMed: 9048669]
356.
Kuzniecky R. Symptomatic occipital lobe epilepsy. Epilepsia. 1998;39(Suppl 4):S24–31. [PubMed: 9637590]
357.
Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differentiation from migraine. Epilep Disord. 1999;1:205–16. [PubMed: 10937155]
358.
Taylor I, Scheffer IE, Berkovic SF. Occipital epilepsies: identification of specific and newly recognized syndromes. Brain. 2003;126:753–69. [PubMed: 12615636]
359.
Panayiotopoulos CP. Occipital seizures and related epileptic syndromes. In: Panayiotopoulos CP, editor. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999. pp. 101–228.
360.
Panayiotopoulos CP. Idiopathic photosensitive occipital spikes seizures. In: Panayiotopoulos CP, editor. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999. pp. 241–55.
361.
Panayiotopoulos CP. Basilar migraine: a review. In: Panayiotopoulos CP, editor. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999. pp. 303–8.
362.
Manford M, Hart YM, Sander JW, Shorvon SD. The National General Practice Study of Epilepsy. The syndromic classification of the International League Against Epilepsy applied to epilepsy in a general population. Arch Neurol. 1992;49:801–8. [PubMed: 1524512]
363.
Panayiotopoulos CP. Elementary visual hallucinations in migraine and epilepsy. J Neurol Neurosurg. Psychiatry. 1994;57:1371–4. [PMC free article: PMC1073189] [PubMed: 7964814]
364.
Panayiotopoulos CP. Elementary visual hallucinations, blindness, and headache in idiopathic occipital epilepsy: differentiation from migraine. J Neurol Neurosurg Psychiatry. 1999;66:536–40. [PMC free article: PMC1736305] [PubMed: 10201433]
365.
Panayiotopoulos CP. Idiopathic childhood occipital epilepsies. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 3rd. London: John Libbey & Co Ltd; 2002. pp. 203–27.
366.
Panayiotopoulos CP. Differentiating occipital epilepsies from migraine with aura, acephalgic migraine and basilar migraine. In: Panayiotopoulos CP, editor. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999. pp. 281–302.
367.
Russell WR, Whitty CWM. Studies in traumatic epilepsy 3. Visual fits. J Neurol Neurosurg Psychiatr. 1955;18:79–96. [PMC free article: PMC503221] [PubMed: 14381917]
368.
Ludwig BI, Marsan CA. Clinical ictal patterns in epileptic patients with occipital electroencephalographic foci. Neurology. 1975;25:463–71. [PubMed: 1169704]
369.
Penfield W, Rasmussen T. The cerebral cortex of man:A clinical study of localisation of function. New York: The Macmillan Company; 1957.
370.
Babb TL, Halgren E, Wilson C, Engel J, Crandall P. Neuronal firing patterns during the spread of an occipital lobe seizure to the temporal lobes in man. Electroencephalogr Clin Neurophysiol. 1981;51:104–7. [PubMed: 6161774]
371.
Guerrini R, Dravet C, Genton P, Bureau M, Bonanni P, Ferrari AR, et al. Idiopathic photosensitive occipital lobe epilepsy. Epilepsia. 1995;36:883–91. [PubMed: 7649127]
372.
Walker MC, Smith SJ, Sisodiya SM, Shorvon SD. Case of simple partial status epilepticus in occipital lobe epilepsy misdiagnosed as migraine: clinical, electrophysiological, and magnetic resonance imaging characteristics. Epilepsia. 1995;36:1233–6. [PubMed: 7489701]
373.
Thom M, Moran NF, Plant GT, Stevens JM, Scaravilli F. Cortical dysplasia with angiodysgenesis and chronic inflammation in multifocal partial epilepsy. Neurology. 1999;52:654–7. [PubMed: 10025810]
374.
Maillard L, Vignal JP, Anxionnat R, TaillandierVespignani L. Semiologic value of ictal autoscopy. Epilepsia. 2004;45:391–4. [PubMed: 15030502]
375.
Blanke O, Landis T, Spinelli L, Seeck M. Out-of-body experience and autoscopy of neurological origin. Brain. 2004;127:243–58. [PubMed: 14662516]
376.
Herschel JFW. Familiar lectures on scientific aspects. London: Alexander Straham; 1866. p. 406.
377.
Plant GT. The fortification spectra of migraine. B MJ. 1986;293:1613–7. [PMC free article: PMC1351873] [PubMed: 3545388]
378.
Gowers WR. Abiotrophy and other lectures. Philadelphia: P. Blackinston’s Son & Co; 1904. Subjective sensations of sight and sound.
379.
Schmidt EM, Bak MJ, Hambrecht FT, Kufta CV, O’Rourke DK, Vallabhanath, et al. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex. Brain. 1996;119:507–22. [PubMed: 8800945]
380.
Airy H. On a distinct form of transient hemiopsia. Philos Trans R Soc Lond. 1870;160:247–70.
381.
Bien CG, Benninger FO, Urbach H, Schramm J, Kurthen M, Elger CE. Localizing value of epileptic visual auras. Brain. 2000;123:244–53. [PubMed: 10648433]
382.
Maillard L, Vignal JP, Anxionnat R, TaillandierVespignani L. Semiologic value of ictal autoscopy. Epilepsia. 2004;45:391–4. [PubMed: 15030502]
383.
Blanke O, Landis T, Spinelli L, Seeck M. Out-of-body experience and autoscopy of neurological origin. Brain. 2004;127:243–58. [PubMed: 14662516]
384.
Critchley M. Butterworths Medical Dictionary. London: Butterworth & Co (Publishers) Ltd; 1986.
385.
Shahar E, Barak S. Favorable outcome of epileptic blindness in children. J Child Neurol. 2003;18:12–6. [PubMed: 12661932]
386.
Panayiotopoulos CP. Basilar migraine? Seizures, and severe epileptic EEG abnormalities. Neurology. 1980;30:1122–5. [PubMed: 7191504]
387.
Ayala G. Status epilepticus amauroticus. Boll Accad Med Roma. 1929;55:288–90.
388.
Barry E, Sussman NM, Bosley TM, Harner RN. Ictal blindness and status epilepticus amauroticus. Epilepsia. 1985;26:577–84. [PubMed: 4076063]
389.
Sawchuk KS, Churchill S, Feldman E, Drury I. Status epilepticus amauroticus. Neurology. 1997;49:1467–9. [PubMed: 9371947]
390.
Williamson PD, Engel J Jr. Complex partial seizures. In: Engel J Jr, Pedley TA, editors. Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 557–66.
391.
Ito M, Adachi N, Nakamura F, Koyama T, Okamura T, Kato M, et al. Multi-center study on post-ictal headache in patients with localization-related epilepsy. Psychiatry Clin Neurosci. 2003;57:385–9. [PubMed: 12839519]
392.
Ito M, Adachi N, Nakamura F, Koyama T, Okamura T, Kato M, et al. Characteristics of postictal headache in patients with partial epilepsy. Cephalalgia. 2004;24:23–8. [PubMed: 14687009]
393.
Blau JN. Classical migraine: symptoms between visual aura and headache onset. Lancet. 1992;340:355–6. [PubMed: 1353815]
394.
Plazzi G, Tinuper P, Cerullo A, Provini F, Lugaresi E. Occipital lobe epilepsy: a chronic condition related to transient occipital lobe involvement in eclampsia. Epilepsia. 1994;35:644–7. [PubMed: 8026411]
395.
Gobbi G, Bertani G. Italian Working Group on Coeliac Disease and Epilepsy. Coeliac disease and epilepsy. In: Gobbi G, Andermann F, Naccarato S, Banchini G, editors. Epilepsy and other neurological disorders in coeliac disease. London: John Libbey & Company Ltd; 1997. pp. 65–79.
396.
Berkovic SF. Progressive myoclonuc epilepsies. In: Engel J Jr, Pedley TA, editors. Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. pp. 2455–68.
397.
Roger J, Genton P, Bureau M, Dravet C. Progressive myoclonus epilepsies in childhood and adolescence. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, editors. Epileptic syndromes in childhood and adolescence. London: John Libbey & Company Ltd; 1992. pp. 381–400.
398.
Minassian BA. Lafora’s disease: towards a clinical, pathologic, and molecular synthesis. Pediatr Neurol. 2001;25:21–9. [PubMed: 11483392]
399.
Hirano M, DiMauro S. Primary Mitochondrial Diseases. Epilepsy. In: Engel J Jr, Pedley TA, editors. A comprehensive textbook. Philadelphia: Lippincott-Raven; 1997. pp. 2563–70.
400.
Gobbi G, Andermann F, Naccarato S, Banchini G, editors. Epilepsy and other neurological disorders in coeliac disease. London: John Libbey & Company Ltd; 1997.
401.
Lawn N, Laich E, Ho S, Martin R, Faught E, Knowlton R, et al. Eclampsia, hippocampal sclerosis, and temporal lobe epilepsy: accident or association? Neurology. 2004;62:1352–6. [PubMed: 15111673]
402.
Minassian BA. Progressive myoclonus epilepsy with polyglucosan bodies: Lafora disease. Adv Neurol. 2002;89:199–210. [PubMed: 11968446]
403.
Salanova V, Andermann F, Olivier A, Rasmussen T, Quesney LF. Occipital lobe epilepsy: electroclinical manifestations, electrocorticography, cortical stimulation and outcome in 42 patients treated between 1930 and 1991. Surgery of occipital lobe epilepsy. Brain. 1992;115:1655–80. [PubMed: 1486456]
404.
Welch KM. Pathogenesis of migraine. Semin Neurol. 1997;17:335–41. [PubMed: 9474713]
405.
Ogunyemi A, Adams D. Migraine-like symptoms triggered by occipital lobe seizures: response to sumatriptan. Can J Neurol Sci. 1998;25:151–3. [PubMed: 9604138]
406.
Panayiotopoulos CP. Difficulties in differentiating migraine and epilepsy based on clinical and EEG findings. In: Andermann F, Lugaresi E, editors. Migraine and epilepsy. Boston: Butterworths; 1987. pp. 31–46.
407.
Andermann F, Zifkin B. The benign occipital epilepsies of childhood: an overview of the idiopathic syndromes and of the relationship to migraine. Epilepsia. 1998;39(Suppl 4):S9–23. [PubMed: 9637589]
408.
Hart YM, Andermann F. Migraine aura, seizures, and temporal lobe epilepsy. Adv Neurol. 1999;81:145–52. [PubMed: 10609011]
409.
Andermann F. Migraine and the benign partial epilepsies of childhood:evidence for an association. Epilep Disord. 2000;2(Suppl 1):S37–S39. [PubMed: 11231222]
410.
Kim SK, Lee DS, Lee SK, Kim YK, Kang KW, Chung CK, et al. Diagnostic performance of [18F]FDG-PET and ictal [99mTc]-HMPAO SPECT in occipital lobe epilepsy. Epilepsia. 2001;42:1531–40. [PubMed: 11879363]
411.
Russell MB, Olesen J. A nosographic analysis of the migraine aura in a general population. Brain. 1996;119:355–61. [PubMed: 8800932]
412.
Bickerstaff ER. Basilar artery migraine. Lancet. 1961;i:15–7.
413.
Bickerstaff ER. Impairment of consciousness in migraine. Lancet. 1961;ii:1057–9. [PubMed: 13868977]
414.
Marks DA, Ehrenberg BL. Migraine-related seizures in adults with epilepsy, with EEG correlation. Neurology. 1993;43:2476–83. [PubMed: 8255443]
415.
Terzano MG, Parrino L, Pietrini V, Galli L. Migraine-epilepsy syndrome:intercalated seizures in benign occipital epilepsy. In: Andermann F, Beaumanoir A, Mira L, Roger J, Tassinari CA, editors. Occipital seizures and epilepsies in children. London: John Libbey & Company Ltd; 1993. pp. 93–9.
416.
Slatter KH. Some clinical and EEG findings in patients with migraine. Brain. 1968;91:85–98. [PubMed: 4966863]
417.
Barlow CF. Headaches and migraine in childhood. Oxford: Blackwell Scientific Publications Ltd; 1984.
418.
Camfield PR, Metrakos K, Andermann F. Basilar migraine, seizures, and severe epileptiform EEG abnormalities. Neurology. 1978;28:584–8. [PubMed: 565890]
419.
De Romanis F, Buzzi MG, Assenza S, Brusa L, Cerbo R. Basilar migraine with electroencephalographic findings of occipital spike-wave complexes: a long-term study in seven children. Cephalalgia. 1993;13:192–6. [PubMed: 8358777]
420.
Panayiotopoulos CP. Basilar migraine. Neurology. 1991;41:1707. [PubMed: 1922834]
421.
Williamson PD, Thadani VM, Darcey TM, Spencer DD, Spencer SS, Mattson, et al. Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery. Ann Neurol. 1992;31:3–13. [PubMed: 1543348]
422.
Kramer G. The limitations of antiepileptic drug monotherapy. Epilepsia. 1997;38(Suppl 5):S9–S13.
423.
Cockerell OC, Johnson AL, Sander JW, Shorvon SD. Prognosis of epilepsy: a review and further analysis of the first nine years of the British National General Practice Study of Epilepsy, a prospective population-based study. Epilepsia. 1997;38:31–46. [PubMed: 9024182]
424.
Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne TR, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 1985;313:145–51. [PubMed: 3925335]
425.
Wyllie E, editor. Principles and Practice. 1993. The treatment of epilepsy.
426.
Shorvon S, Dreifuss FE, Fish D, Thomas D, editors. The treatment of epilepsy. Oxford: Blackwell Science Ltd; 1996.
427.
Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W.B. Saunders; 2000.
428.
Shorvon S. Handbook of epilepsy treatment. Oxford: Blackwell Science; 2000.
429.
Pellock JM, Dodson WE, DeBourgeois BF. Pediatric epilepsy. New York: Demos; 2001.
430.
Shorvon S, Perucca E, Fish D, Dodson E. The treatment of epilepsy. In: Shorvon S, Perucca E, Fish D, Dodson E, editors. The treatment of epilepsy (2nd edition) 2nd. Oxford: Blackwell Publishing; 2004. pp. 1–913.
431.
Leach JP, Marson T, Chadwick D. New antiepileptic drugs: revolution or marketing spin? Practical Neurology. 2001;1:70–81.
432.
Marson AG, Chadwick DW. New drug treatments for epilepsy. J Neurol Neurosurg Psychiatry. 2001;70:143–7. [PMC free article: PMC1737219] [PubMed: 11160458]
433.
Marson AG, Hutton JL, Leach JP, Castillo S, Schmidt D, White S, et al. Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review. Epilepsy Res. 2001;46:259–70. [PubMed: 11518627]
434.
Baulac M. New antiepileptic drugs: new therapeutic options. Rev Neurol (Paris) 2002;158:46–54. [PubMed: 11997751]
435.
Bialer M, Walker MC, Sander JW. Pros and cons for the development of new antiepileptic drugs. CNS. Drugs. 2002;16:285–9. [PubMed: 11994018]
436.
Bialer M. New antiepileptic drugs currently in clinical trials: is there a strategy in their development? Ther Drug Monit. 2002;24:85–90. [PubMed: 11805728]
437.
Brunbech L, Sabers A. Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents. Drugs. 2002;62:593–604. [PubMed: 11893228]
438.
Duncan JS. The promise of new antiepileptic drugs. Br J Clin Pharmacol. 2002;53:123–31. [PMC free article: PMC1874286] [PubMed: 11851635]
439.
Hachad H, Ragueneau-Majlessi I, Levy RH. New antiepileptic drugs: review on drug interactions. Ther Drug Monit. 2002;24:91–103. [PubMed: 11805729]
440.
Leppik IE. Three new drugs for epilepsy: levetiracetam, oxcarbazepine, and zonisamide. J Child Neurol. 2002;17(Suppl 1):S53–S57. [PubMed: 11918464]
441.
Perucca E. Marketed new antiepileptic drugs: are they better than old-generation agents? Ther Drug Monit. 2002;24:74–80. [PubMed: 11805726]
442.
Schwabe SK. Challenges in the clinical development of new antiepileptic drugs. Ther Drug Monit. 2002;24:81–4. [PubMed: 11805727]
443.
Temple RJ, Himmel MH. Safety of newly approved drugs: implications for prescribing. JAMA. 2002;287:2273–5. [PubMed: 11980528]
444.
Weinstein SL, Conry J. New antiepileptic drugs: comparative studies of efficacy and cognition. Curr Neurol Neurosci Rep. 2002;2:134–41. [PubMed: 11898480]
445.
Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Loiseau P, Perucca E. Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V) Epilepsy Res. 2001;43:11–58. [PubMed: 11137386]
446.
Smith D, Chadwick D. The management of epilepsy. J Neurol Neurosurg Psychiatry. 2001;70(Suppl 2):II15–II21. [PMC free article: PMC1765559] [PubMed: 11385045]
447.
Walker MC, Sander JW. The impact of new antiepileptic drugs on the prognosis of epilepsy: seizure freedom should be the ultimate goal. Neurology. 1996;46:912–4. [PubMed: 8780062]
448.
Walker MC, Sander JW. Difficulties in extrapolating from clinical trial data to clinical practice: the case of antiepileptic drugs. Neurology. 1997;49:333–7. [PubMed: 9270558]
449.
Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic- clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. NEJM. 1992;327:765–71. [PubMed: 1298221]
450.
Marson AG, Williamson PR, Clough H, Hutton JL, Chadwick DW. Carbamazepine versus Valproate Monotherapy for Epilepsy: A Meta-analysis. Epilepsia. 2002;43:505–13. [PubMed: 12027911]
451.
Shorvon SD. The choice of drugs and approach to drug treatments in partial epilepsy. In: Shorvon S, Perucca E, Fish D, Dodson E, editors. The treatment of epilepsy (2nd edition) Oxford: Blackwell Publishing; 2004. pp. 317–33.
452.
French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, et al. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62:1252–60. [PubMed: 15111659]
453.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol. 2003;2:473–81. [PubMed: 12878435]
454.
Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet. 2004;43:707–24. [PubMed: 15301575]
455.
Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci. U.S.A. 2004;101:9861–6. [PMC free article: PMC470764] [PubMed: 15210974]
456.
Tran TA, Leppik IE, Blesi K, Sathanandan ST, Remmel R. Lamotrigine clearance during pregnancy. Neurology. 2002;59:251–5. [PubMed: 12136066]
457.
de Haan GJ, Edelbroek P, Segers J, Engelsman M, Lindhout D, Devile-Notschaele M, et al. Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology. 2004;63:571–3. [PubMed: 15304599]
458.
LaRoche SM, Helmers SL. The new antiepileptic drugs: scientific review. JAMA. 2004;291:605–14. [PubMed: 14762040]
459.
Marson AG, Kadir ZA, Chadwick DW. New antiepileptic drugs: a systematic review of their efficacy and tolerability. BMJ. 1996;313:1169–74. [PMC free article: PMC2352473] [PubMed: 8916746]
460.
Marson AG. Meta-analysis of antiepileptic drug trials. In: Duncan JS, Sisodiya S, Smalls JE, editors. Epilepsy 2001. From science to patient. Oxford: Meritus Communications; 2001. pp. 317–28.
461.
Hovinga CA. Levetiracetam: a novel antiepileptic drug. Pharmacotherapy. 2001;21:1375–88. [PubMed: 11714211]
462.
Cochrane AL. Effectiveness and efficiency:Random reflections on health services. Cambridge: Cambridge University Press; 1989. [PubMed: 2691208]
463.
Montenegro MA, Cendes F, Noronha AL, Mory SB, Carvalho MI, Marques LH, et al. Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy. Epilepsia. 2001;42:539–42. [PubMed: 11440350]
464.
Barcs G, Halasz P. Effectiveness and tolerance of clobazam in temporal lobe epilepsy. Acta Neurol Scand. 1996;93:88–93. [PubMed: 8741124]
465.
Sheth RD, Ronen GM, Goulden KJ, Penney S, Bodensteiner JB. Clobazam for intractable pediatric epilepsy. J Child Neurol. 1995;10:205–8. [PubMed: 7642889]
466.
Singh A, Guberman AH, Boisvert D. Clobazam in long-term epilepsy treatment: sustained responders versus those developing tolerance. Epilepsia. 1995;36:798–803. [PubMed: 7635098]
467.
Remy C. Clobazam in the treatment of epilepsy: a review of the literature. Epilepsia. 1994;35(Suppl 5):S88–S91. [PubMed: 8039479]
468.
Schmidt D. Clobazam for treatment of intractable epilepsy: a critical assessment. Epilepsia. 1994;35(Suppl 5):S92–S95. [PubMed: 8039480]
469.
Buchanan N. Clobazam in the treatment of epilepsy: prospective follow-up to 8 years. J R Soc Med. 1993;86:378–80. [PMC free article: PMC1293003] [PubMed: 8371242]
470.
Munn R, Farrell K. Open study of clobazam in refractory epilepsy. Pediatr Neurol. 1993;9:465–9. [PubMed: 7605555]
471.
Canadian Clobazam Cooperative Group. Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Epilepsia. 1991;32:407–16. [PubMed: 2044502]
472.
Canadian Study Group for Childhood Epilepsy. Clobazam has equivalent efficacy to carbamazepine and phenytoin as monotherapy for childhood epilepsy. Epilepsia. 1998;39:952–9. [PubMed: 9738674]
473.
Bawden HN, Camfield CS, Camfield PR, Cunningham C, Darwish H, Dooley JM, et al. The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy. Epilepsy Res. 1999;33:133–43. [PubMed: 10094425]
474.
Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21:904–19. [PubMed: 11718497]
475.
Schmidt D. Modern management of epilepsy: Rational polytherapy. Baillieres Clin Neurol. 1996;5:757–63. [PubMed: 9068879]
476.
Baulac M. Rational conversion from antiepileptic polytherapy to monotherapy. Epileptic Disord. 2003;5:125–32. [PubMed: 14684346]
477.
French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62:1261–73. [PubMed: 15111660]
478.
Schmidt D, Elger C, Holmes GL. Pharmacological overtreatment in epilepsy: mechanisms and management. Epilepsy Res. 2002;52:3–14. [PubMed: 12445955]
479.
Panayiotopoulos CP, Benbadis SR, Covanis A, Dulac O, Duncan JS, Eeg-Olofsson O, et al. Efficacy and tolerability of the new antiepileptic drugs; commentary on the recently published practice parameters. Epilepsia. 2004;45:1646–9. [PubMed: 15571526]
480.
Deckers CL, Knoester PD, de Haan GJ, Keyser A, Renier WO, Hekster YA. Selection criteria for the clinical use of the newer antiepileptic drugs. CNS. Drugs. 2003;17:405–21. [PubMed: 12697000]
481.
Briggs DE, French JA. Levetiracetam safety profiles and tolerability in epilepsy patients. Expert Opin Drug Saf. 2004;3:415–24. [PubMed: 15335297]
482.
Leppik IE, Biton V, Sander JW, Wieser HG. Levetiracetam and Partial Seizure Subtypes: Pooled Data from Three Randomized, Placebo-controlled Trials. Epilepsia. 2003;44:1585–7. [PubMed: 14636332]
483.
Depondt C, Yuen ACW, Mula M, Liu RSN, Mitchell TN, Bell GS, et al. Long-term retention and efficacy of levetiracetam in a large cohort of patients with chronic epilepsy. Epilepsia. 2004;45(Suppl 7):1.315.
484.
Cramer JA, Arrigo C, Van Hammee G, Gauer LJ, Cereghino JJ. Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group. Epilepsia. 2000;41:868–74. [PubMed: 10897159]
485.
Patsalos PN. Levetiracetam. Reviews in Contemporay Pharmacology. 2004;13:1–168.
486.
Guberman AH, Besag FM, Brodie MJ, Dooley JM, Duchowny MS, Pellock JM, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia. 1999;40:985–91. [PubMed: 10403224]
487.
Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61:570–1. [PubMed: 12939444]
488.
Leppik IE. Zonisamide. Epilepsia. 1999;40(Suppl 5):S23–S29. [PubMed: 10530691]
489.
Panayiotopoulos CP. Idiopathic generalised epilepsies. In: Panayiotopoulos CP, editor. A guide to epileptic syndromes and their treatment. Oxford: Bladon Medical Publishing; 2002. pp. 114–60.
490.
Arroyo S, Anhut H, Kugler AR, Lee CM, Knapp LE, Garofalo EA, et al. Pregabalin Add-on Treatment: A Randomized, Double-blind, Placebo-controlled, Dose-Response Study in Adults with Partial Seizures. Epilepsia. 2004;45:20–7. [PubMed: 14692903]
491.
Huppertz HJ, Feuerstein TJ, Schulze-Bonhage A. Myoclonus in epilepsy patients with anticonvulsive add-on therapy with pregabalin. Epilepsia. 2001;42:790–2. [PubMed: 11422338]
492.
Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology. 2002;42:229–36. [PubMed: 11804619]
493.
French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003;60:1631–7. [PubMed: 12771254]

Footnotes

*

The terms focal and partial seizures are synonymous and are interchangeable. Focal seizures or focal epilepsies are the preferred term.

*

This section is primarily based on an extensive review from ancient to current times, studies and numerous illustrative cases in a previous monograph of mine, which I have updated appropriately.328,359–361

Copyright © 2005, Bladon Medical Publishing, an imprint of Springer Science+Business Media.
Bookshelf ID: NBK2605