Chapter  12:  Symptomatic and Probably Symptomatic Focal Epilepsies: Topographical Symptomatology and Classification

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.

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.

“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.

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:

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.

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

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.

Autonomic Disturbances and Ictus Emeticus

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

Figure 12.3

Cardiac asystole soon after the onset of a right-sided (more...)

Figure 12.3

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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. Brain MRI was normal.

Figure courtesy of Dr Michael Koutroumanidis, Department of Clinical Neurophysiology and Epilepsies, St. Thomas’ Hospital, London, UK.

Figure 12.3

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.

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-sided^102–104 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 laughter^105–108 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

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.

Electroencephalography

Figure 12.4

EEG samples from two patients with hippocampal epilepsy. (more...)

Figure 12.4

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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 no spikes or other ‘conventional’ epileptogenic abnormalities. Right: The conventional epileptogenic focus of sharp and slow wave complexes is localised in the right anterior temporal electrode. The patient had right hippocampal sclerosis.

Figure 12.4

Figure 12.5

EEG of a woman aged 24 with LTLE. Note the marked (more...)

Figure 12.5

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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.

Figure 12.5

“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.

Figure 12.4

Figures 12.2

12.3

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

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.

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.

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 fear^87,155 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.

Definitions

Figure 12.11

Video EEG of a 43-year-old man during complex focal (more...)

Figure 12.11

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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: (a) the frequent, but irregular, appearance of sharp–slow wave complexes, which are mainly localised in the bifrontal electrodes with left-sided preponderance; (b) the relative preservation of alpha activity; and (c) brief discontinuation of the ictal discharge. The numbers show the actual time of the recording.

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

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

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 life^{40,142,144–148}

• 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 year^180,182

   • 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.

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:

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

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

Figure 12.4

Figure 12.4

Figure 12.4

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.

Figure 12.2

Figures 12.2

12.3

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

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

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.

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.

Seizures from the Supplementary Sensorimotor Area

Figure 12.9

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.

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.

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:

Epigastric auras do not occur.

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. 

   

   Figure 12.10

   Typical absence seizures of late onset due to frontal (more...)

   

   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 GSWD were entirely symmetrical; there was nothing to suggest that these were symptomatic absences. Clinically, during the GSWD, the woman made minor and occasional errors on breath counting, with consistent eyelid flickering. In her daily life, these were manifested as “losing control of thoughts, repeating simple phrases and occasional mild jerking of the head to the right”. This could last for a few seconds to a minute and once she had non-convulsive status epilepticus with mild confusion and expressive dysphasia. Right: Video EEG 6 years later showed that she continued to have similar GSWD with right-sided asymmetry

   ‘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}

“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

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

MRI

Figure 12.8

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

Electroencephalography

Figure 12.11

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.

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 choreoathetosis^277–279

• 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

Figure 12.10

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.

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

Somatosensory Seizures

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

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:

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

Electroencephalography

Interictal EEG

Figure 12.17

Interictal EEG of a 5-year-old girl with extensive (more...)

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. Clinically she had frequent and intractable focal sensory-motor seizures.

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

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

Elementary Visual Hallucinations

Figure 12.18

Visual seizures as perceived and drawn by a patient (more...)

Figure 12.18

.

Visual seizures as perceived and drawn by a patient with an interesting form of symptomatic occipital epilepsy (case detailed in ref ³⁷³).

From Panayiotopoulos (1999)³⁵⁷ with the permission of the Editor of Epileptic Disorders.

Figure 12.18

Figure 12.18

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 migraine^365,366 and reviewed them exhaustively from ancient times.³⁵⁹ The main conclusions of these studies are briefly described here.

Figure 12.18

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

“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

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

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.

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.

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.

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}

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.

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

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

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.

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.

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.

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

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.

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.

Electroencephalography

EEG is essential, but certain limitations should be recognised.

Differentiating Visual Seizures from Migraine

Visual Seizure

“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

Table 12.3

Differential diagnosis of occipital seizures from (more...)

Table 12.3

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

	Occipital epilepsy	Migraine with aura	Basilar migraine
Visual hallucinations
Duration for seconds to a minute	Exclusive	None	None
Duration for 1–3 minutes	Frequent	Rare	Rare
Duration for 4–30 minutes	Rare	As a rule	As a rule
Daily in frequency	As a rule	Rare	None
Mainly coloured circular patterns	As a rule	Rare	Exceptional
Mainly achromatic or black and white linear patterns	Exceptional	As a rule	Rare
Moving to the opposite side of the visual field	Exclusive	None	None
Expanding from the centre to the periphery of a visual hemifield	Rare	As a rule	Frequent
Evolving to blindness	Rare	Rare	As a rule
Evolving to tonic deviation of eyes	Exclusive	None	None
Evolving to impairment of consciousness without convulsions	Frequent	Rare	Frequent
Evolving to impairment of consciousness with convulsions	Frequent	Exceptional	Rare
Associated with post-ictal/post-critical headache	Frequent	As a rule	Frequent
Blindness and hemianopia
Without other preceding or following symptoms	Frequent	None	Frequent
Other neurological symptoms
Brain stem symptoms	None	None	Exclusive
Post-ictal/post-critical vomiting	Rare	Frequent	Frequent
Post-ictal/post-critical headache
Post-ictal or post-critical severe headache	Frequent	As a rule	Frequent

Modified from Panayiotopoulos (1999)³⁵⁷ with the permission of the editor of Epileptic Disorders.

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:

“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.

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).

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:

“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.

“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

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

Clinical Practice in Developed Countries

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).

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.