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.

According to the NICE Guideline: Epilepsies in children, young people and adults (April 2022):

  • The seizure type(s) and epilepsy syndrome, aetiology, and co-morbidity should be determined.
  • If there is diagnostic uncertainty, individuals should be referred to tertiary services soon (within 4 weeks) for further assessment. 
  • Chapter 5 of the NICE guideline (here) provides information on treating epileptic seizures in children, young people and adults.

The current classification and description of SHE can be found in the Position Statement by the ILAE Taskforce: Epilepsy syndromes with onset at a variable age.

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

  • ILAE Definition and Classification:  https://www.ilae.org/guidelines/definition-and-classification 
  • Perucca P. Genetics of Focal Epilepsies: What do we know and where are we Heading? Epilepsy Currents. 2018;18(6):356-362. doi:10.5698/1535-7597.18.6.356
  • Scheffer IE, Bhatia KP, Lopes-Cendes I, et al. Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain. 1995;118 ( Pt 1):61-73. https://doi.org/10.1093/brain/118.1.61
  • Tinuper P, Bisulli F, Cross JH, Hesdorffer D, Kahane P, Nobili L, Provini F, Scheffer IE, Tassi L, Vignatelli L, Bassetti C, Cirignotta F, Derry C, Gambardella A, Guerrini R, Halasz P, Licchetta L, Mahowald M, Manni R, Marini C, Mostacci B, Naldi I, Parrino L, Picard F, Pugliatti M, Ryvlin P, Vigevano F, Zucconi M, Berkovic S, Ottman R. Definition and diagnostic criteria of sleep-related hypermotor epilepsy. Neurology. 2016 May 10;86(19):1834-42. https://doi.org/10.1212/WNL.0000000000002666 

 

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Page created: 08/24/2021