Chapter 27: Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

INTRODUCTION

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a familial focal epilepsy syndrome characterized by frontal lobe seizures occurring predominantly during light sleep. Although not a common condition, it is increasingly recognized, with over 100 families reported.¹ It was first described in 1994 in families from Australia, Canada, and the United Kingdom,² and subsequently became the first human epilepsy for which an underlying genetic defect was identified. The first mutation to be discovered was in the CHRNA4 gene encoding the α4 subunit of the nicotinic acetylcholine receptor (nAChR),³ a ligand-gated ion channel. The subsequent discovery of further nAChR subunit gene mutations in ADNFLE,^4,5,6 along with ion channel gene mutations in various other familial epilepsy syndromes, led to the concept of channelopathies as the fundamental basis to many epilepsy syndromes.⁷

CLINICAL, ELECTROGRAPHIC, AND IMAGING FINDINGS IN ADNFLE

Clinical Features

Seizure onset is usually in childhood, typically between 8 and 11 years of age, although onset ranges from 1 to 52 years.^8,9 Seizures tend to occur in clusters and arise almost exclusively from sleep, with children usually having 6–8 seizures per night occurring over a few hours.⁸ Seizures most commonly occur as the individual is falling off to sleep, or in the morning toward the end of the normal sleep period. Less commonly seizures occur sporadically throughout the night. Around 25% of patients also have occasional daytime seizures during periods of poor control.^8,9

Semiology is consistent with frontal lobe seizures, with rare secondarily generalized tonic–clonic seizures in some individuals. Although seizure semiology can vary markedly between patients with ADNFLE, it is usually highly stereotyped within a given individual. Subjects are often woken by a nonspecific aura but more frequent auras include a shiver, a feeling of "breath being stuck in the throat," or sensory phenomena in the limbs.⁸ Vocalization, which may be a grunt, moan, or a single word, is very common at onset, and may continue throughout the event.⁸ Motor features are usually prominent, and may take a variety of forms such as frenetic bipedal automatisms, rhythmic axial movements, and asymmetric tonic posturing. Tonic posturing may be severe such that some individuals have bent their bed-head when holding on to it during a seizure. Other individuals have seizures that appear like a generalized tonic–clonic seizure but awareness is preserved. The appearance of the seizure may be bizarre, and misdiagnosis is not uncommon.^8,9 Consciousness is often preserved through the seizures, or may vary in different attacks in an individual, and is usually associated with a sense of fear or panic during the seizure. Not surprisingly, frequent attacks may cause a child to become scared of falling asleep. Seizures are brief, typically less than 1 minute in duration, and are highly stereotyped. They tend to occur in ...