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Midbrain iron content in early Parkinson disease

A potential biomarker of disease status

From the Division of Neurology (W.R.W.M., M.W.) and Department of Biomedical Engineering (M.G.), University of Alberta, Edmonton, Canada.

Address correspondence and reprint requests to Dr Wayne Martin, Movement Disorders Clinic, Glenrose Rehabilitation Hospital, 10230–111 Ave., Edmonton, AB, Canada, T5G 0B7

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the lateral substantia nigra pars compacta (SNc). Our objective was to determine whether, in patients with early PD, SNc changes evident on MRI sequences sensitive to iron content corresponded anatomically to the pathologic changes reported previously, and to correlate these changes to the duration and severity of clinical manifestations of PD.

Methods: Twenty-six untreated patients with early PD and 13 age- and gender-matched control subjects had MRI with a 3 tesla magnet using a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate (R₂*). R₂* was calculated for midbrain and forebrain basal ganglia regions. Clinical features were rated with the Unified Parkinson's Disease Rating Scale.

Results: A difference in measured R₂* values between patients and controls was observed in the lateral SNc (p 0.005). Linear regression indicated a correlation between the lateralized motor score from the clinically most affected side and R₂* values from the opposite lateral SNc (p = 0.01).

Conclusions: High field strength MRI demonstrates lateral substantia nigra pars compacta abnormalities in early Parkinson disease (PD) consistent with increased iron content and corresponding to the known distribution of neuronal loss occurring in this disorder. This may ultimately provide an imaging marker for disease progression in PD, although longitudinal studies are required.

GLOSSARY: AC = anterior commissure; CN = caudate nucleus; GP = globus pallidus; LantGP = left anterior GP; LantPu = left anterior Pu; LlatSNc = left lateral SNc; LlatSNr = left lateral SNr; LmedSNc = left medial SNc; LmedSNr = left medial SNr; LpostGP = left posterior GP; LpostPu = left posterior Pu; PC = posterior commissure; PD = Parkinson disease; Pu = putamen; RantGP = right anterior GP; RantPu = right anterior Pu; RlatSNc = right lateral SNc; RlatSNr = right lateral SNr; RmedSNc = right medial SNc; RmedSNr = right medial SNr; RN = red nucleus; ROI = region of interest; RpostGP = right posterior GP; RpostPu = right posterior Pu; SNc = substantia nigra compacta; SNr = substantia nigra reticulata; TE = echo times; UPDRS = Unified Parkinson's Disease Rating Scale.

wayne.martin{at}ualberta.ca

e-Pub ahead of print on January 2, 2008, at www.neurology.org.

Supported by the Canadian Institutes for Health Research.

Disclosure: The authors report no conflicts of interest.

Received April 14, 2007. Accepted in final form August 8, 2007.