Myoclonic astatic epilepsy

Overview

Myoclonic Astatic Epilepsy (MAE), also known as Doose syndrome, is a rare childhood epilepsy syndrome characterized by sudden onset of multiple seizure types, especially myoclonic (brief muscle jerks) and astatic (sudden loss of muscle tone) seizures. It typically begins in children between the ages of 1 and 5 years, often in previously healthy and developmentally normal individuals. The condition is classified as a generalized epilepsy and is considered part of the spectrum of idiopathic (genetic) generalized epilepsies.

MAE was first described by Dr. Hermann Doose in 1970 and is considered a distinct epileptic syndrome due to its unique seizure types and electroencephalogram (EEG) patterns. Although some children achieve remission, others may develop treatment-resistant epilepsy and experience developmental regression. Early recognition and appropriate management are crucial for optimizing outcomes.

Causes

The exact cause of myoclonic astatic epilepsy is not fully understood, but it is believed to be primarily genetic in origin. Unlike structural or metabolic epilepsies, MAE typically shows no identifiable abnormalities on brain imaging or metabolic tests.

Genetic and Biological Factors

• Idiopathic epilepsy: MAE is considered idiopathic, meaning it arises without a clear underlying structural cause.

• Family history: Many children with MAE have a family history of epilepsy or febrile seizures, suggesting a genetic predisposition.

• Gene mutations: Mutations in genes such as SCN1A, SLC6A1, and GABRG2 have been reported in some cases, though no single gene has been definitively linked to all cases of MAE.

Environmental or acquired causes are not typically associated with MAE, and most children are otherwise healthy before the onset of seizures.

Symptoms

The clinical hallmark of MAE is the presence of multiple seizure types, primarily myoclonic and astatic seizures. The combination of these seizure types can significantly impact the child's safety and daily functioning.

Seizure Types in MAE

• Myoclonic seizures: Sudden, brief jerks of the arms or legs, often occurring multiple times per day

• Astatic seizures (drop attacks): Sudden loss of muscle tone resulting in head drops or falls

• Generalized tonic-clonic seizures: Convulsive seizures that may occur during sleep or illness

• Absence seizures: Brief lapses in awareness, less common but can occur in some children

Other Symptoms and Features

• Normal development prior to seizure onset

• Potential regression in speech, behavior, or cognition after seizure onset

• Frequent injuries from drop attacks due to sudden falls

• Seizures often triggered or worsened by fever, illness, or sleep deprivation

Seizures often begin abruptly and may increase in frequency over days to weeks. In some cases, children may enter a state of frequent, hard-to-control seizures called status epilepticus or epileptic encephalopathy.

Diagnosis

Diagnosis of myoclonic astatic epilepsy is based on clinical history, seizure types, EEG findings, and the exclusion of other epilepsy syndromes or structural brain abnormalities. A prompt and accurate diagnosis is important for guiding treatment decisions.

Diagnostic Criteria

• Onset between 1 and 5 years of age

• Previously normal development before seizure onset

• Presence of myoclonic, astatic, or myoclonic-astatic seizures

• No structural brain abnormalities on MRI

Investigations

• Electroencephalogram (EEG):

  • Generalized 2–3 Hz spike-and-wave or polyspike-and-wave discharges

  • EEG abnormalities often increase with sleep

• Brain MRI: Typically normal, used to rule out structural causes

• Genetic testing: May be recommended to identify possible mutations

The diagnosis may take time to confirm, especially if seizures are subtle or overlap with other syndromes such as Lennox-Gastaut syndrome or epilepsy with myoclonic-atonic seizures.

Treatment

Treatment for myoclonic astatic epilepsy involves antiseizure medications and, in some cases, dietary therapy. MAE can be difficult to manage, and a tailored approach is essential. Early intervention is associated with better outcomes.

1. Antiseizure Medications

• Valproic acid: Often the first-line treatment due to broad-spectrum efficacy

• Ethosuximide: May be used for associated absence seizures

• Clobazam or clonazepam: Benzodiazepines that may reduce seizure frequency

• Levetiracetam: Sometimes used as an adjunctive agent

• Avoid carbamazepine and phenytoin: These may worsen seizures in MAE

2. Ketogenic Diet

• High-fat, low-carbohydrate diet that can significantly reduce seizures in refractory cases

• Often considered in children who do not respond well to medication

• Requires supervision by a dietitian and medical team

3. Other Therapies

• Vagus nerve stimulation (VNS): May be considered in drug-resistant cases

• Developmental support: Physical, occupational, and speech therapy if developmental delays occur

Regular follow-up with a pediatric neurologist is necessary to monitor treatment efficacy, adjust medications, and assess developmental progress.

Prognosis

The prognosis of myoclonic astatic epilepsy varies widely. Some children achieve seizure remission and maintain normal development, while others may have persistent seizures and cognitive impairment. Early diagnosis and aggressive management can improve outcomes.

Favorable Prognostic Factors

• Early response to valproic acid or ketogenic diet

• Normal cognitive development at the time of seizure onset

• Fewer types of seizures and absence of status epilepticus

Poor Prognostic Indicators

• Frequent or uncontrolled seizures

• Development of tonic seizures or generalized epileptic encephalopathy

• Regression in speech or cognitive function

Many children with MAE experience remission of seizures by adolescence, although some may continue to have learning or behavioral difficulties. With comprehensive care and early intervention, many children with MAE can lead fulfilling lives.