Sleep-related hypermotor epilepsy (SHE)

Overview

  • Sleep-related hypermotor epilepsy is a focal syndrome characterized by motor seizures occurring from sleep, often in clusters or multiple times a night.
  • The seizures are commonly asymmetric dystonic/tonic or hyperkinetic.
  • The syndrome encompasses the entities previously known as nocturnal frontal lobe epilepsy (NFLE) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
  • The EEG is typically normal.
  • Aetiology may be structural or genetic or unknown.
  • This epilepsy may be drug-resistant.  A subset has responded to carbamazepine.

Demographics

Prevalence: 

  • Estimated prevalence of non familial form: 1.8-1.9/100,000.

Age of onset and clinical picture: 

  • Usually first two decades, peak in adolescence (11-14y). Range 2m - 64y.
  • Normal neurological exam.

Aetiology:

  • Aetiology may be structural, genetic or acquired. In most cases aetiology is unknown.
  • Familial and sporadic SHE show similar features.
  • Minority of familial cases have genetic mutation. Familial SHE is usually inherited in autosomal dominant fashion with 70% penetrance. 
    • Associated genes include for example: CHRNA4 related to neuronal acetylcholine receptor; KCNT1 (severe phenotype), GATORI defects (often with structural defects, DEPDC5 (m Tor pathway)

Signs | Symptoms

Seizure semiology: 

  • Seizure frequency is typically high and clustering is common.
  • Seizures occur predominantly during NREM sleep, commonly soon after falling asleep but may occur at any time of night. Awake seizures 27-45% at some time in life.
  • May be preceded by arousal or distinct aura. Vocalization at onset is common.
  • Seizures are typically abrupt, <2mins
  • Seizures have a high degree of stereotypy and may include:
    • Hypermotor seizures with vocalization and emotional facial expression, fear; autonomic features
    • Asymmetric tonic/dystonic seizures with or without head deviation;
    • Paroxysmal arousals
    • Epileptic nocturnal wandering
    • Focal to bilateral clonic seizures can occur.
  • Awareness during seizures is not uncommon. 

Neurological and mental state:

  • Usually normal intelligence.
  • Intellectual disability and behavioural disorder have been reported, especially in the familial form associated with KCNT1.

Differential diagnosis:

- Parasomnias: 

  • Typically longer in duration, > 10 mins.
  • Usually occur in isolation and do not cluster. 
  • Occur from deep NREM sleep (Stage 3-4), typically in first half of night, usually 1-2 hours after falling asleep.
  • Symptoms of parasomnias vary from attack to attack and may include sleepwalking and performing complex tasks.
  • Clear recall not reported following parasomnia

- Non-epileptic seizures.
 

- Other focal epilepsies.
 

Investigations

EEG: 

  • Interictal and ictal EEG typically normal.
  • May show frontal spikes in sleep.

MRI:

  • Most commonly normal; structural abnormality may be found-focal cortical dysplasia or less commonly acquired lesion.

Prognosis

  • Many patients respond to first line treatment.
  • Poorer prognostic signs: Neurological or intellectual disability, imaging abnormality, seizures in wakefulness.
     

Management

  • A subset has responded to carbamazepine in low doses, however, it is ineffective in at least a third.
  • Surgery has been utilized, especially in relation to focal cortical dysplasia.

 

References

  1. Brain 1995; 118: 61-73
  2. Neurology  2016; 86: 1834-1842
  3. ILAE classification: website
  4. Epilepsy Curr. 2018, 18: 356-62 
     

 

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Page created: 08/24/2021