What is Landau‑Kleffner syndrome?

What is Landau-Kleffner Syndrome?

Landau-Kleffner syndrome (LKS) is an acquired epileptic aphasia disorder affecting children aged 3-8 years who have developed age-appropriate speech but then experience language regression with verbal auditory agnosia, abnormal epileptiform EEG activity, behavioral disturbances, and sometimes overt seizures. 1

Core Clinical Features

Language Regression

• Children lose previously acquired language skills, developing verbal auditory agnosia (inability to understand spoken language despite normal hearing) 1
• The language loss is the defining feature that distinguishes LKS from other childhood epileptic encephalopathies 2
• Regression typically occurs after a period of normal language development, usually between ages 3-8 years 1

Epileptiform EEG Abnormalities

• A highly distinctive EEG abnormality is present and associated with development of marked aphasia 3
• The epileptiform activity is activated during sleep 2
• EEG shows abnormal findings with generalized seizure discharge during sleep, with spikes often noted in bilateral frontal and temporal regions 4

Seizures

• Overt seizures occur in some but not all patients 1
• When present, seizures are part of the clinical presentation but the language regression is the primary concern 1

Behavioral Disturbances

• Behavioral changes accompany the language regression 1
• Aggressive behavior and difficulty maintaining posture have been reported 4

Diagnostic Evaluation

When to Suspect LKS

• Any child with developmental regression, particularly language regression, should have LKS ruled out 3
• Unusual features in a child's history, particularly regression, should prompt additional evaluations including EEG 3

Diagnostic Workup

• EEG is essential and will show the characteristic epileptiform abnormalities 3, 4
• Neuroimaging (MRI) is typically normal 4
• Cerebrospinal fluid analysis is typically normal 4
• Systemic and neurological examination is usually normal 4

Relationship to Other Conditions

Distinction from ESES

• LKS is distinct from electrical status epilepticus in slow wave sleep (ESES), though the two syndromes have some overlap 2
• In LKS, the loss of function is limited to language, whereas in ESES there is a wider spectrum of cognitive impairment 2

Distinction from Autistic Regression

• Language regression also occurs in younger children with autistic regression, and many have epileptiform EEGs 2
• Whether these children are part of an extended LKS spectrum is controversial due to differences in age of onset, clinical phenotype, and EEG findings 2
• Children with autism spectrum disorder can develop LKS as a separate condition 5

Prognosis and Natural History

Generally Poor Prognosis Without Treatment

• LKS is associated with a generally poor prognosis for recovery of speech without intervention 6
• Early diagnosis and prompt medical treatment are important for achieving better long-term prognosis 1
• Treatment should probably not be delayed more than 1-2 months after initial diagnosis 1

Treatment Approach

Medical Management

• Valproic acid or diazepam is often empirically chosen as initial therapy 1
• Other antiepileptic drugs reported to be beneficial include ethosuximide, clobazam, and clonazepam 1
• Carbamazepine and possibly phenobarbital and phenytoin may occasionally exacerbate the syndrome and should be avoided 1

Corticosteroid Therapy

• Corticosteroid therapy should probably not be delayed more than 1-2 months after initial diagnosis 1
• Various regimens including oral prednisone and high-dose intravenous pulse corticosteroids have been reported effective 1
• Oral corticosteroids usually need to be maintained for a long period to prevent relapses 1

Surgical Treatment

• Multiple subpial transection is reserved for patients who have not responded to multiple medical therapies 1
• In one surgical series, 79% of patients (11 of 14) who had not used language to communicate for at least 2 years were speaking after surgery—a rate of sustained improvement considered unusual in this disorder 6
• Success depends on demonstrating that severe epileptogenic abnormality is unilateral in origin despite bilateral electrographic manifestation 6

Supportive Interventions

• Speech therapy, including sign language, should be used in all patients 1
• Classroom and behavioral interventions are helpful in managing LKS 1