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Primary torsion dystonia (PTD) has been conceptualized as a disorder of the basal ganglia. However, recent data suggest a widespread pathology involving motor control pathways. In this report, we explored whether PTD is associated with abnormal anatomical connectivity within motor control pathways. We used diffusion tensor magnetic resonance imaging (DT-MRI) to assess the microstructure of white matter. We found that fractional anisotropy, a measure of axonal integrity and coherence, was significantly reduced in PTD patients in the pontine brainstem in the vicinity of the left superior cerebellar peduncle and bilaterally in the white matter of the sensorimotor region. Our data thus support the possibility of a disturbance in cerebello-thalamocortical pathways as a cause of the clinical manifestations of PTD. Keywords diffusion tensor MRI; primary dystonia; motor control; cerebellum; brainstem; basal ganglia; torsinA Dystonia is characterized as a syndrome of sustained muscle contractions that often cause abnormal postures or involuntary repetitive movements. Primary torsion dystonia (PTD) can be distinguished from other etiologic subgroups of dystonia by the presence of dystonia as the only or primary clinical sign and the absence of another etiology. 1 The most frequent genetic cause of PTD is a heterozygous GAG deletion in the gene DYT1, which results in the loss of a glutamic acid residue in the encoded protein, torsinA. 1 A less frequent autosomal dominant variant of PTD identified in North American Mennonite families is mappped to a gene on chromosome 8 (DYT6 HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript incomplete penetrance, 3 but the pathophysiological link between mutation carrier status and clinical penetrance is unknown. Although PTD has traditionally been conceptualized as a disorder inherent to the basal ganglia, recent electrophysiological, functional imaging, and anatomical studies have suggested the presence of more widespread pathology involving motor control pathways from the neocortical to the spinal level. [4][5][6][7][8] In a series of PET studies conducted in the resting state, we identified a reproducible abnormal spatial covariance pattern of regional metabolism in DYT1 mutation carriers, even in those without clinical manifestations (non-manifesting carriers). 9,10 This torsion dystoniarelated pattern is characterized by relative metabolic increases in the putamen/globus pallidus, the supplementary motor area (SMA), and the lateral cerebellum. Changes in basal ganglia metabolism are also found in the DYT6 genotype. These mutation carriers showed a significant metabolic reduction in the putamen that is more pronounced in those affected clinically (manifesting carriers). 11 In both PTD genotypes, regional metabolic increases in the pre-SMA and the parietal association cortices distinguished mutation carriers with clinical manifestations of dystonia from their non-manifesting counterparts. 11 These results are consistent with the notion of...

These findings are consistent with the hypothesis that schizophrenia and bipolar disorder may represent a continuum of global disconnectivity in the brain but that regional functional specificity may not be evident.

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Diffusion-weighted MRI in CJD demonstrates specific-signal abnormalities that correlate well with areas of the most severe and characteristic neuropathologic changes.