Brain neurotransmitters in dystonia musculorum deformans

We examined histologically and biochemically the brains of two patients with generalized childhood-onset dystonia musculorum deformans. We found no important histologic changes in the basal ganglia, cerebral cortex, higher brain-stem nuclei, locus ceruleus, or raphe nuclei. Similarly, the activity of choline acetyltransferase and the levels of gamma-aminobutyric acid and glutamic acid in the cerebral cortex and basal ganglia were within the control range. In contrast, the norepinephrine concentrations were markedly and consistently decreased in the lateral and posterior hypothalamus, mamillary body, subthalamic nucleus, and locus ceruleus. The serotonin level was subnormal in the dorsal raphe nucleus, as was the dopamine level in the nucleus accumbens and, in one of the two cases, in the striatum. Elevated concentrations of norepinephrine were found in the septum, thalamus, colliculi, red nucleus, and dorsal raphe nucleus; of serotonin, in the globus pallidus, subthalamic nucleus, and locus ceruleus; and of 5-hydroxyindoleacetic acid, in the globus pallidus, subthalamic nucleus, and nuclei raphe centralis inferior and obscurus. The level of homovanillic acid showed little consistent change in the regions examined. We conclude that some of these monoamine changes, especially the pronounced apparent disturbance of noradrenergic brain mechanisms, may represent a basic neurochemical abnormality in dystonia musculorum deformans and may thus be relevant to the pathoneurophysiology and treatment of this disorder.