Striatal morphology correlates with sensory abnormalities in unaffected relatives of cervical dystonia patients.
Structural grey matter abnormalities have been described in adult-onset primary torsion dystonia (AOPTD). Altered spatial discrimination thresholds are found in familial and sporadic AOPTD and in some unaffected relatives who may be non-manifesting gene carriers. Our hypothesis was that a subset of unaffected relatives with abnormal spatial acuity would have associated structural abnormalities. Twenty-eight unaffected relatives of patients with familial cervical dystonia, 24 relatives of patients with sporadic cervical dystonia and 27 control subjects were recruited. Spatial discrimination thresholds (SDTs) were determined using a grating orientation task. High-resolution magnetic resonance imaging (MRI) images (1.5 T) were analysed using voxel-based morphometry. Unaffected familial relatives with abnormal SDTs had reduced caudate grey matter volume (GMV) bilaterally relative to those with normal SDTs (right Z = 3.45, left Z = 3.81), where there was a negative correlation between SDTs and GMV (r = -0.76, r(2) = 0.58, p < 0.0001). Familial relatives also had bilateral sensory cortical expansion relative to unrelated controls (right Z = 4.02, left Z = 3.79). Unaffected relatives of patients with sporadic cervical dystonia who had abnormal SDTs had reduced putaminal GMV bilaterally compared with those with normal SDTs (right Z = 3.96, left Z = 3.45). Sensory abnormalities in some unaffected relatives correlate with a striatal substrate and may be a marker of genetic susceptibility in these individuals. Further investigation of grey matter changes as a candidate endophenotype may assist future genetic studies of dystonia.
Walsh
Richard A
RA
Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. richardawalsh@gmail.com
Whelan
Robert
R
O'Dwyer
John
J
O'Riordan
Sean
S
Hutchinson
Siobhan
S
O'Laoide
Risteard
R
Malone
Kevin
K
Reilly
Richard
R
Hutchinson
Michael
M
D000328:Adult; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001480:Basal Ganglia Diseases / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology; D004185:Disability Evaluation; D004193:Discrimination Learning / Q000502:physiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology; D009483:Neuropsychological Tests; D011699:Putamen / Q000473:pathology / Q000503:physiopathology; D012678:Sensation Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D013028:Space Perception / Q000502:physiology; D014103:Torticollis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology