Doose Syndrome
Doose Syndrome, also known as Myoclonic-Atonic Epilepsy (MAE), is a rare genetic epilepsy syndrome of childhood. The ILAE classifies it as a developmental and epileptic encephalopathy, recognising that the epileptic activity itself contributes to developmental and cognitive difficulties.
Presentation and Clinical Features
Age of Onset: Onset typically occurs in early childhood, between 2 and 5 years of age, and is more common in boys.
Seizure Characteristics: The hallmark seizures are myoclonic-atonic seizures, which are often described as “jerk-and-fall” attacks.
Myoclonic Component: A brief jerk of the head, trunk, or limbs.
Atonic Component: An abrupt loss of muscle tone, causing the child to suddenly fall to the ground. This can lead to serious head and facial injuries.
Other Seizure Types: Patients may also experience other seizure types, including generalised tonic-clonic seizures (GTCS), absences, and myoclonic seizures without a subsequent atonic fall. Atonic seizures can also occur in isolation, causing a sudden head drop or fall.
Developmental Impact: The condition is considered an epileptic encephalopathy because a significant proportion of children experience cognitive and behavioural difficulties, including learning disabilities and attention deficits.
Genetics: Approximately one-third of children with Doose Syndrome have a family history of epilepsy or febrile seizures, and a genetic link is strongly suspected, often overlapping with the spectrum of Genetic Epilepsy with Febrile Seizures Plus (GEFS+).
Investigations
Diagnosis: The diagnosis is primarily based on the distinctive clinical history of myoclonic-atonic seizures in a young child.
EEG: The EEG is crucial and shows generalised or bi-parietal slow spike-and-wave discharges (typically 2-3 Hz). These discharges are particularly prominent during drowsiness and sleep.
Neuroimaging and Genetic Testing: A brain MRI is usually normal. Genetic testing should be considered to rule out specific genetic causes that mimic the syndrome, such as SLC2A1 gene mutations associated with GLUT1 deficiency, as this has a specific treatment.
Management and Prognosis
Treatment: Seizure control can be challenging, but a combination of antiepileptic drugs (AEDs) is often effective.
First-Line Medications: Valproate and Levetiracetam are often considered first-line agents. Clobazam and Lamotrigine may also be used.
Medications to Avoid: Carbamazepine, phenytoin, and oxcarbazepine can worsen the myoclonic and atonic seizures and should be avoided.
Dietary Therapy: The Ketogenic Diet is highly effective in controlling seizures in Doose Syndrome and is often considered a first-line treatment, especially for drug-resistant cases.
Surgical Options: For highly refractory cases, surgical options like Corpus Callosotomy (dividing the nerve fibres connecting the two cerebral hemispheres) may be considered by a tertiary neurology centre to prevent debilitating drop attacks.
Prognosis: The prognosis is variable. While some children achieve seizure freedom, a significant number have ongoing difficulties with seizures and development. The long-term outcome is often related to the initial seizure control and the presence of developmental comorbidities.