Although classic Landau-Kleffner syndrome (LKS) is rare, the disorders considered its clinical variants are relatively common.1,3,20,21 Tuchman21 has proposed a schema that takes into account cognitive, language, social, and behavioral deficits, age of onset, and the EEG and epilepsy status. LKS is contrasted with autistic epileptiform regression and disintegrative epileptiform disorder. Table: Comparison of Landau-Kleffner Syndrome with autistic and disintegrative disorders

Autistic epileptiform regression

Autistic regression is the most common disorder considered a variant of LKS. The clinical picture differs from LKS in several important respects. Unlike children with LKS, children with autistic regression show impairments in social relatedness, both verbal and nonverbal communication skills, and symbolic play. They also demonstrate a restricted, ritualized pattern of interests and activities. Motor, vocal, or visual stereotypies may be observed. Other behavioral disturbances may include distractibility, hyperactivity, tantrums, and difficulty in making the transition from one activity to another. Cognitive impairment is relatively common in children with autistic spectrum disorders who regress.22

Autistic regression tends to occur between 12 and 36 months, generally earlier than LKS. At this age, the normality of prior development is difficult to ascertain.

About one-fourth of autistic children ultimately experience seizures. Epileptiform EEGs are even more common. In Tuchman and Rapin’s22 cohort of almost 600 children with autistic spectrum disorders, nearly one-third experienced a regression. Of those who regressed, one-third had epilepsy and one-half had epileptiform EEGs. Of those who regressed but did not have epilepsy, one-fifth had epileptiform EEGs. Epileptiform EEGs were thus more common in those who regressed and had epilepsy (60% with epilepsy, 15% without). An epileptiform EEG with or without concurrent epilepsy was more likely to be associated with regression (15% vs. 5%). Thus, almost one-third of this cohort had autistic epileptiform regression (AER).

A number of investigators have reported on individual patients with AER who have responded variably to treatment with antiepileptic drugs.23–28 Some patients have been reported to respond to surgical management (multiple subpial transection). (See Treatment)

Disintegrative epileptiform disorder

Disintegrative disorders involve an even broader range of deficits than are seen in the autistic spectrum disorders. By definition, disintegrative disorders begin after age 2 years and before age 10 years in a previously normal child. Some of these children have seizures or epileptiform EEGs—hence the designation disintegrative epileptiform disorder (DED). Cognitive deterioration tends to be more severe than in the autistic spectrum disorders.

Behavioral disturbances may include:27

• attention deficit
• hyperactivity
• impulsiveness
• aggression
• mood changes
• disinhibition
• psychosis

Comparing 18 DED children with autistic children (51 with speech loss and 145 without speech loss), Kurita and Michiko29 found that by age 7 years (approximately 4 years after regression), mental retardation was significantly more severe in children with DED than in those with autism. Autistic symptoms among the groups were similar.

Treatment responses in DED are reported on a case-study basis.27,30,31 Although not designated as such, patients with DED often are included in series of patients with continuous spikes and waves during slow sleep (CSWS).32–34

Other clinical variants

A single case study documents significant improvement during valproate treatment in a child with severe learning disabilities and an extremely epileptiform EEG without clinical seizures.35 Another single case study documents a child with a prolonged isolated deficit of prosody in association with an epileptiform EEG.36

Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.