Myoclonic Atonic Epilepsy (Doose Syndrome)

Overview

  • Myoclonic atonic seizures are the defining feature.
  • Tonic seizures are not a predominant seizure type in this syndrome.
  • The syndrome is considered an epileptic encephalopathy.
  • The EEG usually has a normal background particularly at onset of syndrome, with frequent generalised discharges of 2 to 4 Hz spike/polyspike waves.
  • Non-convulsive status epilepticus is a frequent feature.
  • Outcome is variable but for a subset is favourable. 
  • Treatment: drugs used in generalised epilepsies, such as: sodium valproate, ethosuximide, clobazam are often efficacious. Early use of the ketogenic diet for drug resistant epilepsy is recommended. 
  • Consider early referral to Paediatric Neurology.

According to the NICE Guideline: The Epilepsies:

  • 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.

Demographics

Prevalence

  • 1 in 10,000 children.
  • ~1% to 2% of all childhood epilepsies.
  • Predominance of male sex, in most series: 2:1. Onset in first year equal.

Age at onset

  • 6 months to 6 years, peak 2-4 years.

Aetiology

  • There is often a strong family history of epilepsy including other epilepsy syndromes.
  • A proportion of these patients are SCN1A positive.
  • Other genes affecting the sodium channel may be seen, SCN1B and SCN2A.
  • SLC2A1 (Glucose Transporter gene) is noted in a small subset of patients (4/84 patients in one series).
  • 14% of 85 patients in one series had pathogenic genetic variants found on exome, including new genes (Epilepsia, 2020).

Signs | Symptoms

Seizure semiology

Myoclonic atonic seizure is the defining seizure type (100%), manifesting with symmetrical myoclonic jerks involving the neck, shoulders, arms and legs, immediately followed by loss of muscle tone (atonic component).  They cause lightning-like falls, head nodding, or bending of the knees.

  • More than half of patients have brief absence seizures, often together with myoclonic jerks, facial myoclonias, and atonic events.
  • Atonic and absence seizures are frequent and sometimes many occur each day.
  • Tonic seizures are not a major feature.
  • Non-convulsive status epilepticus for hours or days affects 1/3 of patients.
  • In 2/3's of patients, febrile and non-febrile generalised tonic-clonic seizures appear first, several months prior to myoclonic atonic seizures.
  • The seizure frequency can become very severe and sometimes refractory to treatment.  

Neurological and mental state

  • Often have normal development prior to the onset of seizures.

Differential diagnosis

  • Lennox Gastaut Syndrome.
  • Atypical childhood epilepsy with centrotemporal spikes.
  • Dravet syndrome.

Investigations

EEG

  • Usually normal background particularly at syndrome onset, with frequent generalised discharges of 2 to 4 Hz spike/polyspike wave. With time, background may show generalised slowing.
  • Epileptogenic activity increases in sleep.
  • Photic stimulation may trigger generalised spike/wave or myoclonic atonic seizures.
  • Non-convulsive status leads to continuous or discontinuous and repetitive 2 to 4 Hz spike/wave.

Neuro Imaging

  • Symptomatic causes need to be excluded.

Prognosis

In publication (Epilepsia 2020) 101 patients with myoclonic atonic epilepsy were studied. A high proportion had significant comorbidity:

  • Intellectual disability - 62%
  • Low adaptive behavioural scores - 69%
  • Autism  - 24%
  • ADHD - 37%

Prognosis dependent on: 

  • Age of onset (younger less favourable)
  • Nature of seizures (for example, presence of tonic seizures and interictal EEG findings)
  • A subset have a favourable outcome.
  • 2/3 achieve seizure remission:
    • Myoclonic atonic seizures remit with higher frequency up to 89%, but may be ongoing tonic-clonic seizures. 
    • Cognitive prognosis strongly linked to whether seizures remit.

Ataxia and motor linguistic disturbances may emerge.

Management

Early referral to paediatric neurology recommended.

Other drugs:

  • levetiracetam, acetazolamide, sulthiame.

Non-convulsive status:

  • steroids

Aggravating AEDs:

  • carbamazepine, vigabatrin.

 Discussion with family

Resources

Epilepsy Action (UK) have information for Parents on Epilepsy with Myoclonic Astatic Seizures (Doose Syndrome)

References

  • Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). J Clin Neurophysiol. 2003 Nov-Dec;20(6):449-61. 
  • Nickels K, Thibert R, Rau S, Demarest S, Wirrell E, Kossoff EH, Joshi C, Nangia S, Shellhaas R; Pediatric Epilepsy Research Consortium. How do we diagnose and treat epilepsy with myoclonic-atonic seizures (Doose syndrome)? Results of the Pediatric Epilepsy Research Consortium survey. Epilepsy Res. 2018 Aug;144:14-19. 
  • Panayiotopoulos CP. The epilepsies: Seizures, syndromes and management: Based on the ILAE classifications and practice parameter guidelines. Chipping Norton, Oxfordshire: Bladen Medical Publishing; 2005.
  • Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence (4th ed).  Montrouge, France: John Libbey Eurotext Ltd; 2005.
  • Scheffer IE, Wallace R, Mulley JC, Berkovic SF. Clinical and molecular genetics of myoclonic-astatic epilepsy and severe myoclonic epilepsy in infancy (Dravet syndrome). Brain Dev. 2001 Nov;23(7):732-5.     
  • Tang S, Pal DK. Dissecting the genetic basis of myoclonic-astatic epilepsy. Epilepsia. 2012 Aug;53(8):1303-13. 
  • Tang, S, Addis, L, Smith, A, et al; EuroEPINOMICS‐RES Consortium. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020; 61: 995– 1007.

 

Last reviewed in November 2020.