Myoclonic-Atonic Epilepsy

Myoclonic atonic epilepsy (Doose syndrome) is a generalised childhood epilepsy syndrome with myoclonic atonic seizures (drop attacks) in a previously normal child, beginning at 2 to 6 years of age (peak 3 to 4), more often in boys. It accounts for 1 to 2% of childhood epilepsies. Family history of epilepsy is found in about a third. Variants in SLC6A1, SYNGAP1 and others may be found.

Pathophysiology. Genetic generalised epilepsy network hyperexcitability, in some cases from glucose transporter or GABA transporter defects.

Sudden myoclonic jerk followed by loss of muscle tone, leading to falls with head injury. Other seizures include generalised tonic clonic, absences, tonic seizures (poor prognostic sign) and non-convulsive status epilepticus. Development before onset is normal. Outcome ranges from remission with normal cognition to persistent seizures and intellectual disability.

Red flags.

• Non-convulsive status epilepticus.
• Tonic seizures or developmental regression.

EEG shows generalised 2 to 3 Hz spike wave and polyspike wave, with a background of parietal theta rhythm, with photosensitivity in some. MRI is normal. Metabolic tests, including CSF glucose (glucose transporter type 1 deficiency), genetic panel or exome sequencing. Exclude Lennox-Gastaut syndrome, Dravet syndrome and progressive myoclonic epilepsy.

Differential diagnosis.

• Lennox-Gastaut syndrome, Dravet syndrome and glucose transporter type 1 deficiency.
• Progressive myoclonic epilepsies, severe myoclonic epilepsy and epilepsy with myoclonic absences.
• Non-epileptic drop attacks and cardiac syncope.

First line drugs.

• Valproate 10 to 15 mg/kg daily, increased to 30 to 60 mg/kg daily in divided doses (avoid in girls of childbearing potential and in mitochondrial disease).
• Lamotrigine (start 0.15 mg/kg daily, increased slowly to 5 to 15 mg/kg daily, halve the dose with valproate).
• Levetiracetam 20 to 60 mg/kg daily.
• Ethosuximide 10 to 20 mg/kg daily for absences.
• Clobazam or topiramate as add on.

Ketogenic diet. Effective in many (and first line in glucose transporter type 1 deficiency), with supervision by a dietitian.

Avoid carbamazepine, oxcarbazepine, phenytoin, vigabatrin and tiagabine, which can worsen myoclonic seizures.

Other options. Corticosteroids and immunoglobulin in refractory cases.

Safety. Protective headgear for drop attacks, and rescue treatment for prolonged seizures (buccal midazolam 0.3 mg/kg, maximum 10 mg).

Monitoring. Seizure diary, EEG, development and drug levels.

Referral and escalation. Refer to paediatric epilepsy services.