Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Binkofski, F.
Right arrow Articles by Klein, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Binkofski, F.
Right arrow Articles by Klein, C.
Related Collections
Right arrow PET
Right arrow Volumetric MRI
Right arrow Parkinson's disease/Parkinsonism
Right arrow Motor Control
Right arrow Basal ganglia
Right arrow All Genetics
NEUROLOGY 2007;69:842-850
© 2007 American Academy of Neurology

Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia

F. Binkofski, MD, K. Reetz, MD, C. Gaser, PhD, R. Hilker, MD, J. Hagenah, MD, K. Hedrich, PhD, T. van Eimeren, MD, A. Thiel, MD, C. Büchel, MD, P. P. Pramstaller, MD, H. R. Siebner, MD and C. Klein, MD

From the Department of Neurology (F.B., K.R., J.H., K.H., C.K.), University Hospital Schleswig-Holstein, Luebeck; Department of Neurology (H.R.S.), University Hospital Schleswig-Holstein, Kiel; Department of Psychiatry (C.G.), University of Jena; Department of Neurology (R.H., A.T.), University of Cologne; Departments of Neurology (T.v.E.) and Systems Neuroscience (C.B.), University Medical Center Hamburg Eppendorf, Hamburg, Germany; Department of Neurology (P.P.P.), Central Hospital and Institute of Genetic Medicine, Eurac-Research, Bolzano-Bozen, Italy; and NeuroImage Nord (F.B., K.R., T.v.E., C.B., H.R.S.), Hamburg-Lübeck-Kiel, Hamburg, Germany.

Address correspondence and reprint requests to Dr. Ferdinand Binkofski, Department of Neurology, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany ferdinand.binkofski{at}neuro.uni-luebeck.de

Background: Mutations in the Parkin and PINK1 genes can cause parkinsonism. Since asymptomatic carriers of a single mutant allele of the Parkin or PINK1 gene display a presynaptic dopaminergic dysfunction in the striatum, they provide a unique in vivo model to study structural and functional reorganization in response to latent nigrostriatal dysfunction. We hypothesized that subclinical nigrostriatal neurodegeneration caused by these mutations would induce morphologic changes in the dysfunctional striatal gray matter.

Methods: In asymptomatic carriers of a heterozygous Parkin (n = 13) or PINK1 (n = 10) mutation and 23 age-and sex-matched individuals without a mutation, we applied observer independent region-of-interest and voxel-based morphometry to high-resolution structural MRIs.

Results: Relative to controls without a mutation, Parkin and PINK1 mutation carriers displayed a bilateral increase in gray matter volume in the putamen and the internal globus pallidus. In 8 of the 13 Parkin mutation carriers, the presynaptic dopaminergic function was studied with 18F-DOPA PET. The metabolic-morphometric regression analysis revealed that the linear decrease in individual presynaptic striatal 18F-DOPA uptake was linked to a reciprocal decrease in the striatal gray matter volume in the putamen bilaterally and in the left caudate nucleus.

Conclusions: The alternative causes of the increased striatal gray matter volume may be either due to excessive levels of neuronal activity caused by chronic dopaminergic dysfunction or due to long-term adaptation to chronic nigrostriatal dysfunction actively compensating for the dopaminergic denervation. In any case, the results indicate that a genetically driven regional dysfunction may be imprinted in the structure of the dysfunctional brain region, for example in the striatum.

*Both authors contributed equally to this work.

This study was sponsored by the Deutsche Forschungsgemeinschaft (Kl-1134-2-2 and Kl-1134-3-1), the PD Foundation, the South Tyrolean Parkinson Association, and the EU-grant GENEPARK (EU-LSHB-CT-2006-037544). F.B., H.R.S., and C.B. were funded by the Bundesministerium für Bildung und Forschung (BMBF) (Neuroimagingzentrum NeuroImage-Nord, grant no. GF GO 01GO0205/-206/-207) and F.B. by (01GW0571). F.B., H.R.S., and C.B. were supported by separate project grants from the Volkswagen Foundation and K.R. and C.K. by intramural grants from the Medical Faculty, University of Luebeck. C.K. is a recipient of a Lichtenberg Career Development Award from the Volkswagen Foundation.

Disclosure: The authors report no conflicts of interest.

Received November 10, 2006. Accepted in final form March 27, 2007.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by AAN Enterprises, Inc.