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Neuropathology of primary adult-onset dystonia

From Queen Square Brain Bank, Department of Molecular Neuroscience (J.L.H., T.G., C.S., T.R.), Sobell Department of Motor Neuroscience and Movement Disorders (S.A.S., J.B., K.P.B.), Department of Molecular Neuroscience (S.G., N.W.W.), and Reta Lila Weston Institute (A.J.L.), University College London Institute of Neurology, Queen Square, London, UK; and Department of Neurology, Neuropathology Division, Mount Sinai School of Medicine, New York, NY (P.S.).

Address correspondence and reprint requests to Dr. Janice Holton, Department of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK j.holton{at}ion.ucl.ac.uk

Background: Idiopathic adult-onset primary dystonia usually affects the upper body and remains focal. Underlying mechanisms are unknown, and there are only limited neuropathologic studies in the literature. Recently, ubiquitinated perinuclear inclusion bodies were found in the brainstem of patients with DYT1-related dystonia. In X-linked recessive dystonia-parkinsonism, neuronal loss in the striosome compartment of the striatum has been described. However, it was unclear whether these changes are characteristic of these particular disorders or an epiphenomenon of dystonic conditions in general.

Methods: Six cases of adult-onset dystonia and four controls were studied using immunohistochemistry to determine the presence of inclusion bodies immunoreactive for torsinA, ubiquitin, and laminA/C in the brainstem. The distribution of calcineurin expressing neurons in the striatum was also determined to ascertain whether there is loss of neurons in the striosome compartment.

Results: In contrast to early-onset dystonia, neuronal inclusions immunoreactive for torsinA, ubiquitin, and laminA/C were not present in the brainstem nuclei. There was no apparent loss of the striatal striosome compartment.

Conclusion: Our findings suggest that the underlying mechanism in the adult-onset primary torsion dystonia is different from that of early-onset DYT1-related dystonia and also DYT3 X-linked recessive dystonia-parkinsonism. Alternative mechanisms may underpin the pathophysiology of adult-onset primary dystonia.

Abbreviations: AD = Alzheimer disease; CAA = cerebral amyloid angiopathy; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; GFAP = glial fibrillary acidic protein; NIA = National Institute on Aging; PD = Parkinson disease; XDP = X-linked recessive dystonia-parkinsonism.

J.H. is supported by the Reta Lila Weston Foundation for Medical Research. S.A.S was supported by the Brain Research Trust, UK. S.G was supported by the Wellcome Trust, UK. The Queen Square Brain Bank is supported by the Reta Lila Weston Foundation for Medical Research and the Progressive Supranuclear Palsy (PSP-Europe) Association.

Disclosure: The authors report no conflicts of interest.

Received April 16, 2007. Accepted in final form August 14, 2007.