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Abstract

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.

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Published In

Neurology®
Volume 70Number 9February 26, 2008
Pages: 695-699
PubMed: 18299520

Publication History

Published online: February 25, 2008
Published in print: February 26, 2008

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J. L. Holton, PhD, FRCPath
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.).
S. A. Schneider, MD
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.).
T. Ganesharajah, BSc
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.).
S. Gandhi, MD
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.).
C. Strand, MSc
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.).
P. Shashidharan, PhD
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.).
J. Barreto, MD
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.).
N. W. Wood, PhD, FRCP
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.).
A. J. Lees, MD, FRCP
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.).
K. P. Bhatia, MD, FRCP
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.).
T. Revesz, MD, FRCPath
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.).

Notes

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 [email protected]

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