Microscopic Neuroanatomic Abnormalities in Autism

Since its initial description in 1943,1 autism has been primarily conceptualized as a behavioral disorder, and for many years it was believed to be the result of parental and environmental influences. With heightened clinical interest in the disorder, coincident with advances in medical technology, however, evidence for an underlying neurologic basis for autism has become increasingly apparent. HISTORICAL NEUROPATHOLOGIC PERSPECTIVE Based largely on the constellation of symptoms that characterize the disorder, various anatomical sites within the brain have been suggested as a possible primary source of pathology in autism. Suspected regions have included the medial temporal lobe,2-5 the thalamic nuclei,6 the basal ganglia,7 and the vestibular system.8 Computed tomographic imaging studies have shown inconsistent findings.9-14 More recently, however, magnetic resonance imaging studies have described abnormalities in portions of the cerebellum and posterior fossa.15-17 Direct microscopic examination of the autistic brain has, until recently, yielded little information. Aarkrog18 reported "slight thickening of the arterioles, slight connective tissue increase in the leptomeninges, and some cell increase" in a frontal lobe biopsy performed on an autistic patient. Later, in 1976, 33 cases of childhood psychosis were reviewed by Darby.19 Although he suggested a possible correlation between limbic system lesions and the affective symptomatology of autism, no consistent neuropathologic findings were found. In 1980, Williams et al20 studied sections of brain from four patients with autistic-like behavior; looking primarily for cell loss and gliosis, they failed to find any consistent abnormalities. MICROSCOPIC NEUROANATOMIC OBSERVATIONS In 1984, anatomic abnormalities were reported in the brain of a 29-year-old man with well-documented autism; the technique of whole brain serial section was used, and the patient was studied in comparison with an identically processed age- and sex-matched control subject.21,22