Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain.

OBJECTIVE: Measures of cholinergic transmitter activity were investigated in patients with autism because of reported neuropathological abnormalities in cholinergic nuclei in the basal forebrain. METHOD: Levels of cholinergic enzyme and receptor activity were measured in the frontal and parietal cerebral cortex of deceased autistic adults, similarly aged normal adults without mental retardation, and nonautistic mentally retarded adults. The immunoreactivity levels of brain-derived neurotrophic factor and nerve growth factor were measured in the basal forebrain. RESULTS: There were no differences between the autistic and comparison groups in choline acetyltransferase or acetylcholinesterase activity in the cerebral cortex and basal forebrain or in muscarinic M(2) receptor or alpha-bungarotoxin binding within the cortex. Cortical M(1) receptor binding was up to 30% lower than normal in the autistic subjects, and the difference reached significance in the parietal cortex. In both the parietal and frontal cortices, differences in nicotinic receptors assessed by [(3)H]epibatidine binding were significant and extensive (65%-73% lower in the autistic group than in the normal subjects); there were no differences in nicotine binding in the basal forebrain. Immunochemical analysis indicated lower levels of both the alpha(4) and beta(2) nicotinic receptor subunits in the parietal cortex. The M(1) receptor abnormality was not evident in the nonautistic group with mental retardation, although the lower [(3)H]epibatidine binding was apparent. In the basal forebrain, the level of brain-derived neurotrophic factor in the autistic group was three times as high as the level of the normal group. CONCLUSIONS: These neurochemical abnormalities implicate the cholinergic system in developmental disorders such as autism and suggest the potential for intervention based on cholinergic receptor modulation.

The painful shoulder.

The shoulder, a very common site of pain syndromes in medical practice, lends itself well to precise clinical analysis and identification of the pain-sensitive structure or structures. Once identified, rational and effective management can be applied, associated with predictably good prognosis. Early identification of the emerging specific syndrome is important in decreasing the duration of the clinical disorder and in achieving optimum return of shoulder function. Laboratory and X-ray studies are not commonly required in diagnosis and management. There are a confusing variety of names attached to the many shoulder pain syndromes; however, there are two most common categories. One is associated with severe pain but little or no limitation of shoulder movement (at least passive movement), in which the pain-sensitive structure is tendon or tendon sheath; the other is associated with both pain and limitation of active and passive motion, in which the pain-sensitive structures are capsule, bursa, and synovium as well as muscle and multiple tendons.