Neuropathology of primary adult-onset dystonia.
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.


CONCLUSIONS
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.
Holton
J L
JL
Queen Square Brain Bank, Department of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK. j.holton@ion.ucl.ac.uk
Schneider
S A
SA
Ganesharajah
T
T
Gandhi
S
S
Strand
C
C
Shashidharan
P
P
Barreto
J
J
Wood
N W
NW
Lees
A J
AJ
Bhatia
K P
KP
Revesz
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology; D020821:Dystonic Disorders / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D002479:Inclusion Bodies / Q000473:pathology; D007797:Laminin / Q000032:analysis; D008297:Male; D018832:Molecular Chaperones / Q000032:analysis; D025801:Ubiquitin / Q000032:analysis
D007797:Laminin; D018832:Molecular Chaperones; C108175:TOR1A protein, human; D025801:Ubiquitin; C089141:laminin gamma 1; C084098:laminin A