Specific pattern of early white-matter changes in pure hereditary spastic paraplegia

TY - JOUR

T1 - Specific pattern of early white-matter changes in pure hereditary spastic paraplegia

AU - Duning, Thomas

AU - Warnecke, Tobias

AU - Schirmacher, Anja

AU - Schiffbauer, Hagen

AU - Lohmann, Hubertus

AU - Mohammadi, Siawoosh

AU - Young, Peter

AU - Deppe, Michael

N1 - © 2010 Movement Disorder Society.

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. Most MR studies on HSP include very heterogeneous samples of patients, and findings were inconsistent. Here, we examined six patients with pure HSP and SPG4 mutations by clinical evaluation, detailed neuropsychological testing, and neuroimaging analyses, including conventional MRI, diffusion tensor imaging (DTI), and brain volumetry. Differences of voxel-wise statistics and ROI-based analysis of DTI data between patients and 32 healthy volunteers were evaluated. Although conventional MRI and brain volumetry were normal, DTI revealed widespread disturbance of white matter (WM) integrity (P < 0.001), mainly affecting the corticospinal tract. With longer disease duration, frontal regions were also involved. The WM changes were also present in subclinical subjects harbouring the pathogenic mutation. These subtle WM abnormalities have functional relevance because they correlated with clinical symptoms. Thus, early alterations of nerve fibres, which can be detected by DTI, might serve as a biological marker in HSP, in particular with respect to future longitudinal studies.

AB - Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. Most MR studies on HSP include very heterogeneous samples of patients, and findings were inconsistent. Here, we examined six patients with pure HSP and SPG4 mutations by clinical evaluation, detailed neuropsychological testing, and neuroimaging analyses, including conventional MRI, diffusion tensor imaging (DTI), and brain volumetry. Differences of voxel-wise statistics and ROI-based analysis of DTI data between patients and 32 healthy volunteers were evaluated. Although conventional MRI and brain volumetry were normal, DTI revealed widespread disturbance of white matter (WM) integrity (P < 0.001), mainly affecting the corticospinal tract. With longer disease duration, frontal regions were also involved. The WM changes were also present in subclinical subjects harbouring the pathogenic mutation. These subtle WM abnormalities have functional relevance because they correlated with clinical symptoms. Thus, early alterations of nerve fibres, which can be detected by DTI, might serve as a biological marker in HSP, in particular with respect to future longitudinal studies.

KW - Adult

KW - Aged

KW - Brain

KW - Female

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Nerve Fibers, Myelinated

KW - Neuropsychological Tests

KW - Pyramidal Tracts

KW - Spastic Paraplegia, Hereditary

U2 - 10.1002/mds.23211

DO - 10.1002/mds.23211

M3 - SCORING: Journal article

C2 - 20669295

VL - 25

SP - 1986

EP - 1992

JO - MOVEMENT DISORD

JF - MOVEMENT DISORD

SN - 0885-3185

IS - 12

ER -