Landau-Kleffner Syndrome

Landau-Kleffner syndrome is a rare childhood epileptic encephalopathy with acquired aphasia (auditory verbal agnosia) and epileptiform EEG activity, especially in sleep. It begins at 3 to 8 years of age with previously normal language development. It is in the spectrum of epilepsy with continuous spike and wave during sleep. Seizures occur in 70 to 80%.

Mutations in GRIN2A are found in about 20%.

Pathophysiology. Frequent epileptiform discharges in temporal parietal language areas disrupt language networks during sleep related plasticity.

Loss of comprehension of spoken language (the child seems deaf), then loss of expressive speech, with behavioural changes (hyperactivity, inattention, aggression). Seizures (focal motor, nocturnal generalised tonic clonic, atypical absences) are often infrequent and may remit by adolescence. Hearing is normal.

Overnight EEG (video EEG) shows continuous or nearly continuous spike and wave in non-REM sleep (centrotemporal and temporal), with a spike wave index above 85% in some. Audiometry and brainstem auditory responses are normal. MRI is normal (exclude structural causes). Neuropsychological and language assessment. Genetic testing for GRIN2A and other variants. Exclude autism, hearing loss, tumour and autoimmune encephalitis.

Differential diagnosis.

• Autism with regression, hearing impairment and developmental language disorder.
• Epilepsy with continuous spike and wave during sleep without aphasia, and self-limited epilepsy with centrotemporal spikes.
• Autoimmune encephalitis and brain tumour.

Early treatment improves language outcomes.

Drugs. Valproate 10 to 15 mg/kg daily, increased to 20 to 40 mg/kg daily in divided doses (avoid in girls of childbearing potential), clobazam 0.25 mg/kg daily, increased to 1 mg/kg daily (maximum 40 mg), levetiracetam 20 to 60 mg/kg daily, ethosuximide 10 to 20 mg/kg daily, or sulthiame. Avoid carbamazepine, oxcarbazepine and phenytoin, which can worsen sleep spike and wave.

Corticosteroids. Prednisolone 1 to 2 mg/kg daily for 1 to 3 months, then tapered over months, or high dose methylprednisolone pulses, with monitoring of blood pressure, glucose and growth. Intravenous immunoglobulin 1 to 2 g/kg monthly is an alternative.

Surgery. Multiple subpial transection in refractory cases.

Language support. Speech and language therapy, sign language and augmentative communication, and educational support.

Monitoring. Language, behaviour, school performance and sleep EEG every 3 to 6 months.

Referral and escalation. Refer to paediatric neurology and speech services.