[S26.004] Pre-Symptomatic Loss Of Cerebral White Matter Integrity In Those At Genetic Risk Of Amyotrophic Lateral Sclerosis

Martin Turner,1Nicola Filippini,1Varan Govind,2Peter Andersen,3Christine Stanislaw,4Eliana Reyes,2Sumaira Hussain,2Joanne Wuu,2Michael Benatar2
1Oxford, United Kingdom, 2Miami, FL, USA, 3Umea, Sweden, 4Atlanta, GA, USA


BACKGROUND:
Studies in pre-symptomatic individuals carrying genetic mutations associated with a high risk of developing a neurodegenerative disease, including those linked to amyotrophic lateral sclerosis (ALS), suggest that pathological changes significantly pre-date the onset of symptoms.
DESIGN/METHODS:
Thirty-two asymptomatic individuals (age 49±12) carrying dominant SOD1 mutations; 31 patients with symptomatic ALS (age 50±9); and 34 healthy controls (age 49±9), underwent diffusion tensor MRI using a 3 Tesla magnet. Analysis of regional white matter tract diffusion eigenvector measures was carried out using tract-based spatial statistics, comparing both affected patients and pre-symptomatic individuals to controls.
RESULTS:
In the affected ALS patients, when compared to controls, fractional anisotropy was reduced in the motor cortex and rostral corticospinal tracts bilaterally, and within the inter-hemispheric motor fibers of the body of corpus callosum. Widespread mean, axial and radial diffusivity white matter tract changes were also observed. Comparing pre-symptomatic individuals to controls, we identified a region of significantly increased axial diffusivity along the temporal lobe projection tracts on the right side, an area of pathology also observed among the ALS patients. Exploratory lowering of the statistical threshold did not reveal contralateral or more widespread pathology in the pre-symptomatic group.
CONCLUSIONS:
Cerebral white matter changes associated with ALS are detectable long before the onset of clinical symptoms, and may initially target extra-motor regions in a highly focal manner. This has profound implications for understanding the pathogenesis of ALS, and offers a potential biomarker for future preventative therapeutic trials.
Study Supported by:
Muscular Dystrophy Association, ALS Association, ALS Recovery Fund, NIH
Category - Neuromuscular and Clinical Neurophysiology (EMG): ALS/Anterior Horn Diseases

Wednesday, April 30, 2014 2:45 PM

S26: Platform Session: Biomarkers in Neuromuscular Diseases (2:00 PM-3:45 PM)

 

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