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Landau-Kleffner syndrome (LKS) is an age-related epileptic encephalopathy where developmental regression occurs mainly in the language domain and the electroencephalographic (EEG) abnormalities are mainly localized around the temporal-parietal regions. The term acquired epileptic aphasia describes the main features of this condition.
ORPHA:98818Classification level: Disorder
The prevalence is difficult to estimate because of heterogeneous definitions. The male-to-female ratio is 2:1.
LKS only affects children and adolescents. The age of onset is thought to range from the ages of 2-8 years. Acquired aphasia in previously normal children is the defining feature of this disorder and it usually presents as verbal auditory agnosia. Expressive aphasia follows the receptive aphasia and spontaneous speech becomes limited. Behavioral problems such as attention deficits, hyperactivity, impulsivity, and distractibility often accompany the language regression. Seizures occur in 2/3 of patients and are generally easy to control and remit spontaneously before adolescence. Approximately 1/3 of patients do not have seizures. Seizure types observed include partial motor (most common), generalized clonic and atypical absence. The disease course is progressive with spontaneous fluctuations in severity over time.
The exact etiology is unknown. Structural brain lesions are very infrequent in LKS patients. Genetic factors may be involved, with GRIN2A (16p13.2) mutations appearing to be causal.
Diagnosis is based on clinical (acquired aphasia) and EEG findings. EEG findings include bilateral centro-temporal, posterior temporal, and parieto-occipital spikes during wakefulness that become much more diffuse and intense during non-rapid eye movement (non-REM) sleep, leading in occasions to electrical status epilepticus in sleep (ESES). ESES is characterized by marked potentiation of epileptiform discharges during the transition from wakefulness to sleep leading to (near-) continuous, bilateral or occasionally lateralized slow spikes and waves that occur during a significant proportion of non-REM sleep. The pattern of ESES in LKS is unilateral or bilateral. A reduction of volume in language development areas of the brain may be observed with MRI volumetric analysis. As of now it is not routine clinical practice to perform genetic tests for GRIN2A in LKS, but testing is available in certain specialized centers.
The differential diagnosis includes any epileptic syndrome with sleep potentiation of epileptiform activity such as continuous spikes and waves during sleep, Panayiotopoulos and Gastaut types of benign childhood occipital epilepsy and rolandic epilepsy (see these terms). It is important to rule out a hearing defect and/or autism that may present initially in a similar way.
An autosomal dominant transmission has been proposed in families with a GRIN2A mutation.
Management and treatment
In those with seizures, several antiepileptic drugs (AEDs) are often effective and seizure control is generally not an issue. Corticosteroids have also been linked to improvements or at least stabilization of language abilities. Subpial transections, a surgical approach that seeks to disrupt the epileptic network while preserving eloquent cortex, have been successful in selected cases. Carbamazepine, oxcarbacepine, phenytoin and phenobarbital are generally avoided due to a risk of exacerbation of epileptiform discharges of ESES. Follow-up with an audiologist is recommended and special education may be necessary.
The prognosis is good in regards to seizures as they are easy to control and remit spontaneously around puberty. Language outcome is characterized by a variable improvement with treatment and/or at around puberty, but without ever returning to the pre-disease state.