Corpus callosum morphology, as measured with MRI, in dyslexic men.

To test the hypothesis of anomalous anatomy in posterior brain regions associated with language and reading, the corpus callosum was imaged in the midsagittal plane with magnetic resonance. The areas of the anterior, middle, and posterior segments were measured in 21 dyslexic men (mean age 27 yrs, SD 6) and in 19 matched controls. As predicted, the area of the posterior third of the corpus callosum, roughly equivalent to the isthmus and splenium, was larger in dyslexic men than in controls. No differences were seen in the anterior or middle corpus callosum. The increased area of the posterior corpus callosum may reflect anatomical variation associated with deficient lateralization of function in posterior language regions of the cortex and their right-sided homologues, hypothesized to differ in patients with dyslexia.

Differential response of seven subjects with autistic disorder to clomipramine and desipramine.

OBJECTIVE: Clomipramine, a serotonin reuptake blocker that has unique antiobsessional properties, was hypothesized to have a different effect from that of desipramine, a tricyclic antidepressant with selective adrenergic effects, for the stereotyped, repetitive behaviors in autism. METHOD: Seven subjects, ages 6-18 years, with autistic disorder completed a 10-week double-blind, crossover trial of clomipramine and desipramine following a 2-week single-blind, placebo phase. RESULTS: Clomipramine was superior to desipramine and placebo, as indicated by standardized ratings of autism and anger as well as ratings of repetitive and compulsive behaviors. Clomipramine and desipramine were equally superior to placebo for ratings of hyperactivity. Parents of all seven subjects elected to have their children continue to take clomipramine after the study. CONCLUSIONS: Clomipramine and desipramine are differentially effective in treating the obsessive-compulsive and core symptoms in autistic disorder. Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Sydenham's chorea: physical and psychological symptoms of St Vitus dance.

Eleven children with Sydenham's chorea (8 girls and 3 boys, mean age = 8.4 +/- 2.2 [SD] years) underwent comprehensive physical, neuropsychologic, and psychiatric examination. The chorea was manifested as dysarthria, gait disturbances, and frequent adventitious movements of the face, neck, trunk, and extremities. Antineuronal antibodies were present in 10 of 11 children. All children exhibited concomitant psychologic dysfunction, specifically obsessive-compulsive symptomatology, increased emotional lability, motoric hyperactivity, irritability, distractibility, and age-regressed behavior. Obsessive-compulsive symptoms were observed in 9 (82%) children, 4 of whom met diagnostic criteria for obsessive-compulsive disorder. These behavioral symptoms began several days to weeks before the chorea was observed, and they waxed and waned in severity along with the motoric abnormalities. These results suggest that psychologic, particularly obsessive-compulsive, symptoms are accompanying manifestations of Sydenham's chorea which may require medical attention.

Exclusion of growth factor gene mutations as a common cause of Sotos syndrome.

Sotos syndrome is characterized by somatic overgrowth, i.e., macrocephaly and tall stature. Because the cause and pathogenesis of Sotos syndrome remain unknown, we selected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) as possible genes mutated in Sotos syndrome. In seven patients with the classic phenotype, we excluded mutations in these growth factor genes. It is possible that these three genes are not involved in the cause of Sotos syndrome, or alternatively, mutations could not be identified in the small number of patients studied.

Posterior fossa abnormalities in children with infantile spasms.

In order to explore possible pathophysiologic involvement of the brain stem in infantile spasms, we retrospectively compared clinical and electroencephalographic (EEG) features of 14 children with infantile spasms who had gross posterior fossa abnormalities on neuroimaging studies with 84 children with infantile spasms who had either normal neuroimaging (n = 19) or supratentorial abnormalities (n = 65). Children with posterior fossa abnormalities how lower mean initial and follow-up developmental quotients compared to those with normal imaging or supratentorial abnormalities alone. Age of onset of infantile spasms, latency to treatment, response to steroids, and follow-up EEG pattern were not significantly different among the three groups. Six children (6%) had Dandy-Walker cysts, an association rarely reported with infantile spasms. We conclude that the presence of posterior fossa abnormalities in patients with infantile spasms portends a relatively poor developmental outcome.

A search for X-chromosome uniparental disomy and DNA rearrangements in the Rett syndrome.

The cause of the Rett syndrome remains unknown but is thought to be related to X-chromosome abnormalities. Restriction fragment length polymorphism analysis was employed to search for X-chromosome DNA rearrangements and uniparental disomy in 16 probands and their families. Eighteen different probes, each specific for an area on either the long or the short arm of the X-chromosome, were used. DNA rearrangements were not detected at any of the tested loci. In addition, at each informative locus evidence of both maternal and paternal contributions was found in all probands. Thus, no evidence of either chromosomal abnormality or uniparental disomy was found in the population studied. If uniparental disomy is indeed a causative genetic mechanism for the Rett syndrome, its occurrence may only be infrequent.

Dysfunctional attention in autistic savants.

A dysfunctional attention hypothesis of the basis of savant skills was tested with a series of computerized tasks that assessed the ability to divide, shift, direct, and sustain attention. Ten healthy men with pervasive developmental disorders and unusual calendar-calculating skill, and 10 age- and sex-matched controls were tested. There were four general findings. First, the savants and controls did not differ on a measure of visual sustained attention. Second, the savants failed to detect rare auditory targets significantly more than did the controls. Third, the savants were unable to efficiently divide their attention when required to detect both visual and auditory targets simultaneously. Finally, deficient orienting or a deficit in shifting selective attention from one stimulus location to another was evidenced in overall slower reaction times for the savants across tasks requiring shifts and redirecting of attention. This deficit was attributed to an inability to disengage attention as a result of deficient orienting and overselectivity.