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Altered Patterns of Regional Cerebral Blood Flow in Patients with Huntington's Disease: A SPECT Study During Rest and Cognitive or Motor Activation

Department of Psychiatry, Program in Neuroscience, and Department of Diagnostic Imaging and Therapeutics, University of Connecticut Medical School, Farmington
Huntington's Disease Program, Hartford Hospital, Hartford, Connecticut

Correspondence: For correspondence or reprints contact: A. Wallace Deckel, PhD, Department of Psychiatry, Program in Neuroscience, Mail Code 2103, University of Connecticut Medical School, 263 Farmington Ave., Farmington, CT 06030-2103.

ABSTRACT

Previous research using functional transcranial Doppler sonography showed that blood flow velocity in the anterior cerebral artery is significantly less in patients with Huntington's disease (HD) than in healthy volunteers while they are completing mazes. The current research used SPECT to study regional cerebral blood flow (rCBF) in patients with HD during rest and maze testing. Methods. Seven patients with HO and 9 healthy volunteers were injected twice with 0.96-1.15 GBq ^99mTc-labeled hexamethyl-propylene amine oxime. During the 10 min after injection, subjects either solved mazes or rested with their eyes open while looking at a modified maze. After SPECT, count density was obtained from 11 brain regions and corrected for decay and injected dose. Two types of data generated from this experiment, including absolute regional counts per pixel in the regions of interest and count density computed as a percentage of activity in the lateral cerebellum, were compared between groups. Results. During rest, the absolute regional count density was greater in the HD brains than in the healthy brains (P < 0.001). Count density was typically between 8% and 13% higher in the HD group than in the healthy group. The single exception was the caudate density, for which the 2 groups had similar values. No significant differences in absolute regional count density were observed between groups during maze testing. When rCBF was calculated as a percentage of cerebellar rCBF, analysis of covariance found decreases in HD caudate density (P < 0.001) and orbital frontal cortex density (P < 0.005) during maze testing. Changes in rCBF in the caudate nucleus predicted gene status (P = 0.0007) and correlated with time to complete the mazes (P < 0.05). Conclusion. Patients with HD showed an increase in resting rCBF for all brain regions measured except the caudate nucleus. When rCBF was calculated as a percentage of cerebellar blood flow, rCBF in the striatum and orbital cortex in patients with HD was less during maze testing than during rest. Although the cause of these rCBF changes in HD patients is unclear, nitric oxide synthase, a regulator of vasomotor activity, may be involved.

Key Words: SPECT • Huntington's disease • cerebral blood flow • striatum • nitric oxide

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