1/6. Striatal dopamine in early-onset primary torsion dystonia with the DYT1 mutation.Although nigrostriatal dopaminergic dysfunction has been suggested in early onset primary torsion dystonia (PTD) with the DYT1 mutation, the actual status of brain dopamine (DA) is unknown. In a DYT1 mutation-positive autopsy patient with PTD, we found that nigral cellularity was normal and that subregional striatal DA levels were within the control range, except for those in the rostral portions of the putamen and caudate nucleus (50% to 54% of control means). Our data suggest that the DYT1 mutation is not associated with significant damage to the nigrostriatal DA system, in keeping with the absence of parkinsonism and levodopa response in this disorder.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
2/6. Two phenotypes and anticipation observed in Japanese cases with early onset torsion dystonia (DYT1) - pathophysiological consideration.Early onset torsion dystonia (DYT1) is a dominantly inherited dystonia caused by a deletion of three bases, GAG, coding glutamic acid, in chromosome 9q34. The protein coded by this gene was named as torsin A. DYT1 is common among the Ashkenazi Jewish population, but has been thought to be rare among Japanese. Among the idiopathic torsion dystonias being followed in this clinic, we found five families with DYT1 by gene analysis. This is the first report of genetically proven Japanese DYT1.The clinical features of five proband cases were divided into two types. One type is postural dystonia with marked trunkal torsion, and the other is action dystonia associated with violent dyskinetic movements. The affected family members in the upper generations presented with focal or segmental dystonia; it was postural dystonia of the legs in the former, and writer's cramp or tremor of the arms in the latter families. There was an asymptomatic carrier in the upper generation. Anticipation in the age of onset and severity of the disease was observed in all families. Medical treatment, including anticholinergics and levodopa, did not show apparent effects, while stereotactic thalamotomy to the nucleus ventralis lateralis (VL) or ventralis intermedius (Vim), with or without posterior ventral pallidotomy, were effective with action dystonia, but not postural dystonia. This study suggests the existence of at least two phenotypes in DYT1, in which different pathways of the basal ganglia are involved.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
3/6. Gamma knife radiosurgery for torsion spasm. Report of two cases.The authors report on two patients who underwent radiosurgery for torsion spasm and evaluate the efficiency of gamma knife radiosurgery (GKS) as an alternative treatment. The first patient was a 33-year-old woman with severe right-sided lower-limb torsion dystonia. The second patient was a 20-year-old man with right-sided upper-limb torsion dystonia. The target was located at the anterior portion of the ventrolateral nucleus. The maximum doses were 150 Gy and 145 Gy, respectively. Double isocenters with a 4-mm collimator were used. Follow up lasted for 18 months and 8 months, respectively. Both patients had excellent clinical improvement 2 to 3 months after GKS, respectively. The authors believe that GKS may be a safe and efficient treatment for torsion spasm.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
4/6. Severe generalised dystonia associated with a mosaic pattern of striatal gliosis.A mosaic pattern of striatal pathology is described in a male who developed severe generalised dystonia from the age of 10 years, and died at the age of 18 years. There was no family history of dystonia, and extensive investigations during his life failed to identify a cause for the dystonia. The caudate nucleus and putamen showed a network of cell loss and gliosis surrounding islands of preserved striatum. Dorsal parts showed confluent gliosis, and ventral parts were spared. The pattern suggested a correlation with patch-matrix organisation, but there was no correlation with the distribution of calbindin immunoreactive cells, which are present in the matrix of the classical striosome-matrix organisation. The pathological findings were unlike those in status marmoratus, perinatal hypoxia-ischaemia, Huntington's disease, and neuroacanthocytosis, but similar to those reported in a 44-year-old man with predominantly cranial dystonia.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
5/6. 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.- - - - - - - - - - ranking = 7keywords = nucleus (Clic here for more details about this article) |
6/6. pathology in brainstem regions of individuals with primary dystonia.Examination of brains from four individuals with the clinical diagnosis of primary dystonia revealed histopathologic abnormalities in two cases. A 29-year-old man with a 15-year history of dystonia musculorum deformans (DMD) had numerous neurofibrillary tangles (NFT) and mild neuronal loss within the locus ceruleus; occasional NFT were also recognized in the substantia nigra pars compacta, pedunculopontine nucleus, and dorsal raphe nucleus. A 68-year-old man with a 35-year history of meige syndrome had moderate-to-severe neuronal loss in several brainstem nuclei, including the substantia nigra pars compacta, locus ceruleus, raphe nuclei, and pedunculopontine nucleus. Infrequent NFT were also noted in substantia nigra. An examination of these and other brain regions in a 10-year-old boy with a 6-year history of DMD and a 50-year-old woman with a 3-year history of spasmodic torticollis did not disclose similar abnormalities.- - - - - - - - - - ranking = 3keywords = nucleus (Clic here for more details about this article) |