Prevalence

• 1 in 10,000 children.
• ~1-2% of all childhood epilepsies.
• Predominance in male children.
• Onset in first year of life is equal in terms of gender.

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 have genetic variants in SCN1A.
• 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).

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, but when they do occur, can be predictive of poorer outcomes.
• Non-convulsive status epilepticus for hours or days affects 30% of children.
• In around 66% of children, 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.

EEG

• Usually normal background particularly at syndrome onset, with frequent generalised discharges of 2 to 4 Hz spike/polyspike wave. With time, the 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.

Neuroimaging

• Symptomatic causes need to be excluded.

101 patients with myoclonic atonic epilepsy were studied. A high proportion had significant comorbidities including (Epilepsia 2020):

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

Prognosis is 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 there may be ongoing tonic-clonic seizures.
  • Cognitive prognosis strongly linked to whether seizures remit.
• Ataxia and motor linguistic disturbances may emerge.

Early referral to paediatric neurology recommended.

• Sodium valproate
• Ethosuximide
• Lamotrigine
• Clobazam
• Levetiracetam
• Combination therapy of sodium valproate and lamotrigine may be helpful.
• In drug-resistant cases, early introduction of the ketogenic diet can be very effective.

Other drugs:

• acetazolamide, sulthiame

Non-convulsive status:

• steroids

Aggravating AEDs:

• carbamazepine, vigabatrin

Discussion with family

• Safety
• Epilepsy Medical Record
• Drug Handout
• Potential of performing baseline educational assessment (through school counsellor).

Resources

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

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 6.5 of the NICE guideline provides information on treating Epilepsy with myoclonic-atonic seizures (Doose syndrome).

The current classification and description of Doose Syndrome can be found in the Position Statement by the ILAE Taskforce: Epilepsy syndromes with onset in childhood.

• Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). J Clin Neurophysiol. 2003;20(6):449-461. https://doi.org/10.1097/00004691-200311000-00007
• Nickels K, Thibert R, Rau S, et al. How do we diagnose and treat epilepsy with myoclonic-atonic seizures (Doose syndrome)? Results of the Pediatric Epilepsy Research Consortium survey. Epilepsy Res. 2018;144:14-19. https://doi.org/10.1016/j.eplepsyres.2018.04.010
• Panayiotopoulos CP. The epilepsies: Seizures, syndromes and management: Based on the ILAE classifications and practice parameter guidelines. Chipping Norton, Oxfordshire: Bladen Medical Publishing; 2005. https://pubmed.ncbi.nlm.nih.gov/20821848/
• 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;23(7):732-735. https://doi.org/10.1016/s0387-7604(01)00272-8   
• Tang S, Pal DK. Dissecting the genetic basis of myoclonic-astatic epilepsy. Epilepsia. 2012;53(8):1303-1313. https://doi.org/10.1111/j.1528-1167.2012.03581.x
• Tang S, Addis L, Smith A, et al. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020;61(5):995-1007. https://doi.org/10.1111/epi.16508