Landau-Kleffner Syndrome

1. Definition

• A rare, age-related epileptic encephalopathy characterized by the subacute onset of Verbal Auditory Agnosia ("word deafness") and rapid language regression in a child with previously normal development.
• Classified under the spectrum of Epilepsy with Continuous Spike-and-Waves during Slow-Wave Sleep (CSWS).

2. Etiology and Pathophysiology

• Genetic: Mutations in the GRIN2A gene (NMDA receptor subunit) are found in ~20% of cases.
• Autoimmune: Presumed autoimmune mechanism in some cases due to response to steroids/IVIG.
• Functional Lesion: Epileptic discharges originating in the posterior temporal lobe (auditory cortex) disrupt the neural networks required for auditory processing and language retention during the critical period of development.

3. Clinical Features

• Age of Onset: Typically 3–6 years (Range 2–8 years).
• Verbal Auditory Agnosia (Hallmark):
  • The child behaves as if deaf, failing to respond to verbal commands despite normal hearing on audiometry.
  • Often misdiagnosed initially as acquired deafness or autism.
• Language Regression:
  • Loss of receptive language (comprehension) is followed by loss of expressive language.
  • Speech becomes "telegraphic," perseverative, or disappears mutism.
  • Non-verbal intelligence and skills usually remain preserved.
• Seizures (~70–75%):
  • Occur in the majority but are often infrequent and easily controlled.
  • Types: Focal motor seizures (most common), generalized tonic-clonic, atypical absence, or myoclonic seizures.
  • Note: ~25–30% of patients may never have clinical seizures, presenting only with aphasia and EEG abnormalities.
• Behavioral: Hyperactivity, attention deficits, and impulsivity are common (frustration due to inability to communicate).

4. Investigations

• Electroencephalogram (EEG) - Gold Standard:
  • Awake: High-amplitude focal spikes/sharp waves, typically bitemporal or posterior temporal.
  • Sleep (Critical): Marked activation of discharges during non-REM sleep. May progress to CSWS/ESES (Electrical Status Epilepticus during Sleep), where spike-wave index >85% of slow-wave sleep.
• Audiometry: Mandatory to rule out sensorineural hearing loss (results are normal in LKS).
• MRI Brain: Usually normal; performed to exclude structural lesions (tumors, inflammation).
• Genetic Testing: Panel for GRIN2A variants.

5. Management

The primary goal is to preserve language function, not just seizure control.

A. Pharmacotherapy

• Corticosteroids (Mainstay for Aphasia):
  • High-dose Prednisolone (2 mg/kg/day) or ACTH. Often required for months to treat the encephalopathy/aphasia.
  • "Pulse" IV Methylprednisolone is used in severe cases.
• Antiepileptic Drugs (AEDs):
  • First-line: Valproate (VPA), Levetiracetam (LEV), Ethosuximide (ESM), Clobazam (CLB).
  • Nocturnal Benzodiazepines: High-dose Diazepam allowed orally/rectally at night to suppress sleep activation.
  • Contraindicated (Warning): Carbamazepine, Oxcarbazepine, and Phenytoin. These sodium channel blockers can worsen the CSWS pattern and language deficits.

B. Surgical/Other

• Multiple Subpial Transections (MST): Considered if medical therapy fails (refractory cases). Involves severing horizontal intracortical fibers to stop seizure spread while preserving vertical functional columns.
• Ketogenic Diet: Adjunctive therapy for refractory cases.
• Speech Therapy: Essential. Introduction of sign language may be necessary if auditory agnosia is profound.

6. Prognosis

• Seizures: Generally good. Remission usually occurs by adolescence (age 12–15 years).
• Language: Guarded/Variable.
  • Many children are left with permanent language deficits.
  • Key Prognostic Factor: Age of onset. Earlier onset (<3 years) carries a worse prognosis for language recovery than later onset (>6 years).
  • Fluctuating course is common ("waxing and waning").