Outcome of multiple subpial transections for autistic epileptiform regression

Abstract

Treatment options for atypical forms of Landau-Kleffner syndrome (LKS) are not well delineated. Many patients with typical LKS fail to respond to antiepileptic drug treatment, but some benefit from multiple subpial transections (MSTs). The authors report seven patients with autism or autistic epileptiform regression who responded in varying degrees to MSTs after failed medical management. These patients derived from an original cohort of 36 children (29 males, seven females, ranging from 2 years, 3 months to 11 years, 3 months, mean age = 5 years, 8 months) with a history of language delay or regression, as well as varying degrees of social and behavioral abnormalities, who were evaluated with video-electroencephalogram (EEG) monitoring over a 2-year period. Fifteen patients had clinical seizures (11 of the 19 children with autistic epileptiform regression and four of 12 autistic children). Epilepsy was refractory to medication in seven. Surgical treatment variously involved MSTs of the left neocortex in temporal, parietal, and frontal regions, often including regions within the classic perisylvian language areas. One patient also had a left temporal lobectomy. In all seven patients, seizure control or EEG improved after MSTs. Language, social, and overall behavior improved to a moderate degree, although improvements were temporary in most. Autistic epileptiform regression resembles LKS in that both may respond to MST. MST is used to treat epilepsy in eloquent regions. The responsiveness of autistic epileptiform regression to MST buttresses the argument that autistic epileptiform regression is a form of focal epilepsy.

Introduction

Acquired epileptiform aphasia, or Landau-Kleffner syndrome (LKS), typically occurs in an otherwise normal, usually male, child between 3 and 7 years of age [1]. Onset of receptive language regression, generally a verbal auditory agnosia, may be sudden or gradual and is usually followed by deterioration of expressive capacities, at times to the point of mutism. Children with LKS may exhibit distractibility, frustration, tantrums, and other behavioral disturbances, presumably in reaction to the language loss. They remain socially responsive and, unlike autistic children, attempt to communicate through other means (i.e., visual and manual). Clinical seizures occur in approximately 75% but are generally easily controlled with medication. The requisite feature of LKS is an epileptiform electroencephalogram (EEG), usually with spike or spike-and-slow wave discharges, most often in the temporal regions bilaterally, sometimes with electrical status epilepticus during sleep. Treatment with traditional antiepileptic drugs (AEDs) often stops seizures, but aphasia is generally unaffected. Corticotropin may produce somewhat better results. Although the prognosis in LKS is guarded, for a small minority of children, early and aggressive treatment with multiple subpial transections (MSTs) in the active epileptogenic site has resulted in complete or partial language recovery [2], [3].

Many of the patients reported with LKS since 1957 deviate from the classic description. This apparent heterogeneity derives from the lack of a specific pathophysiologic definition of LKS. Patients whose developmental language problems predate the onset of regression, whose autistic behaviors are particularly prominent, whose language, behavior, and cognition decline concurrently, or whose language development is delayed from the outset and thus whose regression is minimal (congenital form) have all been reported under the eponym of LKS or LKS variant [4], [5], [6]. Thus the relationship between the autistic spectrum disorders, pervasive developmental disorder, and LKS remains imprecise. Approximately one third of patients on the autistic spectrum experience a language regression, generally before 3 years of age. Approximately one fourth of patients on the autistic spectrum develop epilepsy by adulthood. Epilepsy and epileptiform EEGs are more common in autistic children who experience regression [7], [8]. Whether such children represent a larger, related subgroup of LKS (a pervasive development disorder or autistic spectrum disorder variant or even several) or a biologically distinct syndrome is controversial. Tuchman [6] has labeled the group with autistic regression and epileptiform EEGs or seizures as autistic epileptiform regression (AER).

Response to treatment is even less well defined in the atypical than in the classic LKS group [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. Therefore the authors report the results of surgical treatment, MSTs, in seven children with LKS variants.