Clinical Description
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by clusters of nocturnal motor seizures with a range of manifestations.
Nocturnal seizures. The history may be obtained from the affected individual and witnesses, and supplemented if necessary by video-EEG monitoring.
Seizures may occur in any stage of sleep, although typically in clusters in non-REM (NREM) sleep, most commonly in stage 2 sleep [Picard & Scheffer 2012]. The affected individual often goes back to sleep rapidly after a seizure, only to be awakened by another event.
The seizures are often stereotyped and brief (5 seconds to 5 minutes); they vary from simple arousals from sleep to dramatic hyperkinetic events with tonic or dystonic features. The hyperkinetic manifestations may appear bizarre, sometimes with ambulation, bicycling movements, ballism (flinging or throwing arm movements), and pelvic thrusting movements.
The three distinct sub-classifications of seizure types based on clinical features of the seizures (semiology) and their duration are "paroxysmal arousals," "paroxysmal dystonia," and "episodic wandering."
Paroxysmal arousal is characterized by abrupt recurrent arousals from NREM sleep associated with a stereotypic motor pattern.
Paroxysmal dystonia is characterized by recurrent motor attacks with dystonic-dyskinetic features arising from NREM sleep and usually lasting less than two minutes.
Episodic wandering is somnambulic agitated behavior arising from NREM sleep.
The reported frequency ranges from one to 20 attacks each night, a mean of 20 seizures per month; about 60% of the affected individuals reported more than 15 seizures per month.
Retained awareness during seizures is common and may cause affected individuals to fear falling asleep. A sense of difficulty breathing and hyperventilation may occur, as well as vocalization, clonic features, urinary incontinence, and secondary generalization.
Some individuals experience an aura preceding the seizure during sleep and are aware of the onset. Aura may be nonspecific or may consist of numbness in one limb, fear, a shiver, vertigo, or a feeling of falling or being pushed.
Note: A minority of individuals experience daytime seizures, typically during a period of poor seizure control. Some of the seizures reported are paroxysmal dystonia similar to those during sleep, and others are generalized tonic-clonic seizures, generalized atonic seizures, and focal seizures with impairment of consciousness or awareness.
EEG findings
Cognitive findings. Clinical neurologic examination is normal and intellect is usually preserved [Oldani et al 1996, Nakken et al 1999]; however, in some individuals neuropsychological assessment reveals reduced intellect, cognitive deficits, or psychiatric comorbidity [Khatami et al 1998, Provini et al 1999, Picard et al 2000, Cho et al 2003, Wood et al 2010].
Picard et al [2009] found below-normal general intellect in five (45%) of 11 subjects with special difficulty in executive tasks and concluded that cognitive dysfunction is an integral part of ADNFLE caused by a heterozygous pathogenic variant in the nicotinic receptor (see Phenotype Correlations by Gene).
Magnusson et al [2003] reported an increase in psychiatric symptoms in families with ADNFLE (see Phenotype Correlations by Gene).
Familial variation. Within a family, the manifestations of the disorder may vary considerably; individuals with subtle manifestations may not present for medical attention.
A high incidence of true parasomnias has been reported in relatives of those with ADNFLE [Provini et al 1999]. True parasomnias were distinguished from epileptic seizures because of their age-dependent course, the rarity of episodes, and their being not violent and often not disturbing for the affected individual. They often ended well before the onset of the clear-cut epileptic seizures.
Onset and prognosis. ADNFLE is lifelong but not progressive. Onset ranges from infancy to adulthood. About 80% of affected individuals develop ADNFLE in the first two decades of life; mean age of onset is ten years. As an individual reaches middle age, attacks may become milder and less frequent. Seizures may vary over time; for example, tonic attacks appearing in early childhood may evolve into seizures with dystonic or hyperkinetic components in later childhood.