Sleep-related hypermotor epilepsy

Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is a form of focal epilepsy characterized by seizures which arise during sleep. The seizures are most typically characterized by complex motor behaviors. It is a relatively uncommon form of epilepsy that constitutes approximately 9-13% of cases.^[1][2][3] This disorder is associated with cognitive impairment in at least half of patients as well as excessive daytime sleepiness due to poor sleep quality.^[4] This disorder is sometimes misdiagnosed as a non-epileptic sleep disorder. There are many potential causes of SHE including genetic, acquired injuries and structural abnormalities.^[5]

In 1981, Lugaresi and Cirignotta described a group of 5 patients with paroxysmal attacks of violent movements of the extremities and dystonic-tonic posturing.^[6] It was initially uncertain whether these events constituted seizures or something else. However, the patients had a good clinical response to the anti-seizure medication carbamazepine. Ultimately, the epileptic nature of this condition was confirmed with EEG and suggested that they were coming from the frontal lobe.^[7][8] The term “nocturnal frontal lobe epilepsy” was suggested as a name for this condition. Later in 2014, a consensus conference recommended that the name be changed to sleep-related hypermotor epilepsy.^[9] There were three main justifications for this change: (1) not all seizures arise from the frontal lobe; (2) seizures do not necessarily occur during the night but rather from sleep; (3) hypermotor describes the most common visible clinical manifestation of the seizures.^[9]

Seizures in SHE are brief and usually have an abrupt onset and offset.^[10] The observable clinical manifestations may consist of rapid, hyperkinetic movements as well as dystonic-tonic posturing of the limbs.^[10] Other potential manifestations include brief arousals from sleep or wandering ambulatory behavior.^[11] Non-motor manifestations (such as sensory or emotional phenomenon) are common and retained awareness during seizures may occur.^[5] Seizures usually occur during non-REM sleep.^[11] The frequency of seizures can be very high and as many as dozens may occur every night which results in poor sleep quality.^[12] In addition, many patients with SHE suffer from cognitive impairment and have behavioral/psychological problems.^[10][13] There are many risks associated with nocturnal seizures including concussion, suffocation and sudden unexpected death (SUDEP).

Approximately 86% of SHE cases are sporadic, 14% of patients have a family history of epilepsy and 5% are inherited in an autosomal dominant manner (i.e. autosomal dominant sleep-related hypermotor epilepsy).^[14] Both genetic, structural and multifactorial etiologies can occur.^[5] In structural cases, the most common pathology is focal cortical dysplasia.^[10]

The first described mutation in SHE was found in genes coding for the neuronal nicotinic acetylcholine receptor.^[15] Since then multiple other genes have been identified including KCNT1, DEPDC5, NPRL2, NPRL3, PRIMA1, CABP4, CRH and others.^[10] In some cases, structural and genetic etiologies can coexist such as with mutations in DEPDC5.^[16]

The condition may be difficult to diagnose and misdiagnosis is common.^[9] The subject may be unaware they have a seizure disorder.^[17] To others, the involuntary movements made during sleep may appear no different from those typical of normal sleep.^[18] People who have nocturnal seizures may notice unusual conditions upon awakening in the morning, such as a headache, having wet the bed, having bitten the tongue, a bone or joint injury, muscle strains or weakness, fatigue, or lightheadedness. Others may notice unusual mental behaviors consistent with the aftermath of a seizure.^[19] Objects near the bed may have been knocked to the floor, or the subject may find themselves on the floor.

Diagnosis is based on clinical history but often EEG and/or polysomnography is required. In many patients the EEG can also be unhelpful as seizures may originate from deep in the brain.^[9] Polysomnography can be helpful distinguishing SHE from parasomnias as they often arise from different stages of sleep.^[9]

Like other forms of epilepsy, SHE can be treated with anti-seizure medications.^[10] Adequate control of seizures occur in approximately two-thirds of patients with anti-seizure medications while approximately one-third of patients do not appropriately respond.^[9] The relative efficacy of different medications has not been systematically investigated.^[9] Historically, low-dose carbamazepine has been the preferred medication for SHE and is often considered to be first-line.^[4] Other anti-seizure medications which have been studied for the treatment of SHE and found to have efficacy include: oxcarbazepine, topiramate, lacosamide and perampanel.^[4][20] Epilepsy surgery can be efficacious in refractory patients.^[4] In addition, there have been reports of successfully treating SHE due to mutations in CHRNA4 with nicotine patches.^[4]

• Manford, Mark (2003), Practical Guide to Epilepsy, Butterworth-Heinemann, ISBN 978-0-7506-4621-5