Journal article
Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations
Journal of neuroscience research, Vol.92(12), pp.1723-1732
12/2014
DOI: 10.1002/jnr.23458
PMID: 25156430
Abstract
Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations
- Creators
- Jeremy J Laukka - Wayne State UniversityMalek I Makki - University Children's Hospital of ZurichTori Lafleur - Wayne State University School of MedicineJeffrey Stanley - Wayne State University School of MedicineJohn Kamholz - Wayne State UniversityJames Y Garbern - Wayne State University
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience research, Vol.92(12), pp.1723-1732
- DOI
- 10.1002/jnr.23458
- PMID
- 25156430
- ISSN
- 0360-4012
- eISSN
- 1097-4547
- Number of pages
- 10
- Grant note
- Pelizaeus‐Merzbacher Foundation (to J.Y.G.) NINDS (NS43783 (to J.Y.G.))
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Neurology; Psychiatry
- Record Identifier
- 9984014020502771
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