Brain structure in preclinical Huntington's disease.
BACKGROUND
Huntington's disease (HD) is traditionally conceptualized as a degenerative disease of the striatum. Recent scientific advances, however, have suggested neurodevelopmental contributions and extrastriatal brain abnormalities. This study was designed to assess the morphology of the brain in participants who had previously undergone elective DNA analyses for the HD mutation who did not currently have a clinical diagnosis of HD (preclinical HD subjects).


METHODS
Twenty-four preclinical participants with the gene expansion for HD underwent brain magnetic resonance imaging and were compared with a group of 24 healthy control subjects, matched by gender and age.


RESULTS
Huntington's disease preclinical participants had substantial morphologic differences from controls throughout the cerebrum. Volume of the cerebral cortex was significantly increased in preclinical HD, whereas the basal ganglia and cerebral white matter volume were substantially decreased.


CONCLUSIONS
In individuals with the HD gene mutation who are considered healthy (preclinical for manifest disease), the morphology of the brain is substantially altered compared with matched control subjects. Although decreased volumes of the striatum and cerebral white matter could represent early degenerative changes, the novel finding of enlarged cortex suggests that developmental pathology occurs in HD.
Paulsen
Jane S
JS
Department of Psychiatry, University of Iowa Roy and Lucille Carver College of Medicine, Iowa City, Iowa 52242, USA. jane-paulsen@uiowa.edu
Magnotta
Vince A
VA
Mikos
Ania E
AE
Paulson
Henry L
HL
Penziner
Elizabeth
E
Andreasen
Nancy C
NC
Nopoulos
Peg C
PC
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D003710:Demography; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018911:Trinucleotide Repeats / Q000235:genetics