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Abstract

Objective: To evaluate the integrity of the dorsal striatal dopaminergic innervation in rigid and choreic Huntington disease (HD).
Background: Some patients with HD have an akinetic-rigid phenotype. It has been suggested that nigrostriatal in addition to striatal pathology is present in this subgroup. The authors sought to determine whether in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding could distinguish patients with akinetic-rigid (HDr) from typical choreiform (HDc) HD.
Methods: Nineteen patients with HD (mean age 48 ± 16 years) and 64 normal controls (mean age 50 ± 14 years) underwent (+)-α-[11C]dihydrotetrabenazine (DTBZ) PET imaging. DTBZ blood to brain ligand transport (K1) and tissue to plasma distribution volume (DV) in the caudate nucleus, anterior putamen, and posterior putamen were normalized to the occipital cortex.
Results: The normalized striatal specific DV was reduced in HDr (n = 6) when compared with controls: caudate nucleus −33% (p < 0.001), anterior putamen −56% (p < 0.0001), and posterior putamen −75% (p < 0.0001). Patients with HDc (n = 13) also had reduced striatal DV: caudate nucleus −6% (NS), anterior putamen −19% (p < 0.01), and posterior putamen −35% (p < 0.0001). Patients with HDr had significantly lower striatal (+)-α-[11C]DTBZ binding than HDc patients. After correction for tissue atrophy effects, normalized DV differences were less significant, with values somewhat increased in the caudate, slightly reduced in the anterior putamen, and moderately decreased in the posterior putamen. There were no significant regional differences in K1 reductions among caudate, anterior, and posterior putamen in HD.
Conclusions: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype. Striatal DV reductions were most prominent in the posterior putamen, similar to PD.

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Information & Authors

Information

Published In

Neurology®
Volume 54Number 9May 9, 2000
Pages: 1753-1759
PubMed: 10802780

Publication History

Received: October 25, 1999
Accepted: January 28, 2000
Published online: May 9, 2000
Published in print: May 9, 2000

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Authors

Affiliations & Disclosures

N.I. Bohnen, MD, PhD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
R.A. Koeppe, PhD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
P. Meyer, MD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
E. Ficaro, PhD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
K. Wernette, MSN
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
M.R. Kilbourn, PhD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
D.E. Kuhl, MD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
K.A. Frey, MD, PhD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.
R.L. Albin, MD
From the Departments of Internal Medicine (Division of Nuclear Medicine) (Drs. BohnenKoeppe, Meyer, Ficaro, Wernette, Kilbourn, Kuhl, and Frey), Neurology (Dr. Albin), The University of Michigan Medical School; and Geriatric Research, Education and Clinical Center (Dr. Albin), Veterans Administration Medical Center, Ann Arbor, MI.

Notes

Address correspondence and reprint requests to Dr. Roger L. Albin, Neuroscience Laboratory Building, 1103 E. Huron, Ann Arbor, MI 48104-1687.

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