Rasmussen Encephalitis

Rasmussen encephalitis is a rare, progressive, unilateral inflammatory brain disease with intractable focal seizures, progressive hemiparesis and cognitive decline. It starts mainly in children aged 1 to 10 years (median 6 years), and occasionally in adolescents and adults, with an incidence of about 2 in 10,000,000 each year.

Pathophysiology. T-cell mediated cytotoxic attack on neurons and astrocytes in one hemisphere causes inflammation, neuronal loss and gliosis, with cortical atrophy. The trigger is unknown.

Three stages:

• Prodromal stage (months to years): infrequent seizures and mild hemiparesis.
• Acute stage (4 to 8 months): frequent focal motor seizures, often epilepsia partialis continua, progressive hemiparesis, hemianopia, aphasia (dominant hemisphere) and cognitive decline.
• Residual stage: fixed deficits and persistent but less frequent seizures.

Red flags.

• Epilepsia partialis continua or status epilepticus.
• Rapidly progressive hemiparesis or cognitive decline in a child.

EEG shows unilateral slowing and epileptiform discharges, with later bilateral changes. MRI shows progressive unilateral cortical atrophy, especially the insula and peri-insular region, with T2 or FLAIR hyperintensity and atrophy of the caudate head. CSF may show oligoclonal bands. Brain biopsy shows T-cell encephalitis with microglial nodules and neuronal loss, performed when diagnosis is uncertain. Exclude other causes (autoimmune encephalitis, mitochondrial disease, cortical dysplasia, vasculitis, tumour, infection).

Differential diagnosis.

• Autoimmune encephalitis, mitochondrial disease (POLG, MELAS) and cortical dysplasia.
• Vasculitis, tumour and chronic viral encephalitis.
• Stroke and Sturge-Weber syndrome.

Seizures. Antiseizure drugs (levetiracetam, carbamazepine, lacosamide) have limited effect. Epilepsia partialis continua is especially refractory.

Immunotherapy. Early immunomodulation may slow the course.

• Methylprednisolone 1 g IV daily for 3 to 5 days (or 20 to 30 mg/kg in children), repeated monthly, with oral prednisolone taper.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, repeated monthly, or 2 g/kg monthly.
• Tacrolimus (target trough 5 to 12 ng/mL), rituximab or plasma exchange in selected patients.

Surgery. Functional hemispherectomy or hemispherotomy is the only treatment that stops seizures (seizure freedom in about 70 to 80%). Timing is balanced between loss of function and cognitive decline. Aphasia and hemiparesis often worsen after surgery, but plasticity in children limits long term deficits.

Rehabilitation. Physiotherapy, speech and occupational therapy, and educational support.

Monitoring. Seizure frequency, neurological function, MRI and drug adverse effects.

Referral and escalation. Refer to a paediatric epilepsy surgery centre early.