Landau-Kleffner syndrome

Synonyms: acquired epileptic aphasia

What is Landau-Kleffner syndrome?

Landau-Kleffner syndrome, formerly known as acquired epileptic aphasia, is a rare syndrome that typically presents in early childhood with language regression and seizures.¹

Affected children who have developed age-appropriate speech then experience language regression with verbal auditory agnosia, abnormal epileptiform activity, behavioural disturbances, and sometimes overt seizures.²

Landau and Kleffner initially described acquired epileptic aphasia in 1957. Landau-Kleffner syndrome has three features:³

• An acquired receptive aphasia.

• Temporoparietal spike-wave discharges in the awake state.

• Frequent generalised spike-wave discharges in sleep (electrical status epilepticus in sleep (ESES)).

How common is Landau-Kleffner syndrome? (Epidemiology)

• The syndrome has been thought to be very rare but, with improved diagnostic techniques, the known prevalence may increase significantly.

• Currently, over 200 cases have been described in world literature.

• There is a slight increase in incidence in boys.

• Most cases do not have a well-defined cause. A few cases appear to have been secondary to low-grade brain tumours, closed head injury, neurocysticercosis and demyelinating disease.

Symptoms of Landau-Kleffner syndrome (presentation)¹

• There is gradual language regression after a period of normal development along with seizures, but there is usually no causal relationship.

• Most cases present between 3-7 years of age, with male to female ratio being 2:1.

• The condition initially presents with language problems presenting as word deafness or auditory verbal agnosia, in which the affected individual is unable to comprehend speech.

• Seizures occur in 70%-85% of patients. The onset of seizures is between age 4-10 years and typically stops after age 15. Seizures may be partial, generalised tonic-clonic, absence or myoclonic.

• Abnormal electroencephalogram (EEG) pattern of spike and wave during sleep often precedes language improvement.

• Many affected children have behavioural disturbances, including hyperactivity and decreased attention span, aggression and attacks of rage. Behavioural changes are believed to be due to language impairment.

Differential diagnosis

• This is very broad and includes other causes of epilepsy, autism, hyperactivity and reduced attention span, aggressive (eg, rage attacks), oppositional, or psychotic behaviour and mental retardation. Some patients may appear deaf, autistic or psychotic, or have some features suggesting attention deficit hyperactivity disorder (ADHD).

• Head injury, brain neoplasms (eg, low-grade astrocytoma), and cerebrovascular thromboembolism and neurocysticercosis may all be associated with acquired aphasia, an epileptiform electroencephalogram (EEG) and seizures.

• Neurodegenerative disorders, especially adrenoleukodystrophy, and acute disseminated encephalomyelitis may also produce a similar presentation.

Diagnosing Landau-Kleffner syndrome (investigations)¹

• MRI is essential to rule out cerebrovascular thromboembolism, brain tumours, demyelination, neurodegenerative disease and central nervous system infections.

• Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging reveals decreased metabolism in one or both temporal lobes. Single-photon emission computed tomography (SPECT) of the brain demonstrates decreased perfusion of the left temporal lobe.

• EEG is a basic component in diagnosis, and typically shows abnormal epileptic discharges in children, while clinical seizures are observed in about 70% of cases. EEG shows spike and wave discharges that are widespread, multifocal or shifting, mostly in the temporal region, sometimes unilateral and are particularly exacerbated during sleep.¹

• Brainstem auditory evoked potentials and hearing tests.

Management of Landau-Kleffner syndrome¹

There is no standard treatment regimen and various treatment modalities are used. The treatment options include anticonvulsant drugs, steroids, adrenocorticotropic hormone (ACTH), ketogenic diet, immunoglobulins, and surgery if required. Early use of steroids or ACTH can relieve symptoms and normalise EEG.

• Patients have special educational needs and require speech therapy. Speech therapy, including sign language, and a number of classroom and behavioural interventions, is beneficial.²

• Psychotherapy may be indicated.

Drugs

• Anticonvulsant medications have variable success.

• As initial therapy, valproic acid or diazepam is often used. Subsequently, other anti-epileptic drugs, corticosteroids, or intravenous immunoglobulin (IVIG) therapy are often used.

• Various corticosteroid regimens including oral prednisone, high doses of intravenous pulse corticosteroids, and adrenocorticotrophic hormone (ACTH) have been reported to be effective.²

Surgical

Multiple subpial transection (MST) has led to some clinical improvement in selected patients.⁴

• The cortex is sliced in parallel lines in the midtemporal gyrus and perisylvian area in order to prevent the spread of the epileptiform activity without causing cortical dysfunction.

• This treatment is reserved for patients who have not responded to multiple medical therapies, but has been followed in selected cases by a marked improvement in language skills and behaviour.

• There is no accepted consensus about suitable candidates for this procedure or evidence for its effectiveness.²

Prognosis

The long-term follow-up shows that epilepsy and EEG abnormalities do not always disappear. Language disturbances tend to persist in most patients. Patients tend to have an overall poor quality of life, mostly due to language difficulties.⁵

One study of 29 patients found:⁴

• The prognosis in terms of seizure outcome was good, but outcome of language and cognitive functions was variable.

• Adequate and early treatment management may avoid language and cognitive deterioration.