Abstract Details

Title Grey Matter Correlates of Clinical Variables in Amyotrophic Lateral Sclerosis - A Neuroimaging Study of ALS Motor Phenotype Heterogeneity and Cortical Focality

Topic Anterior Horn

Presentation(s) P06 - (-)

Poster/Presentation
Number 134

Objective

Background BACKGROUND: Body region of onset and motor disability are key components of disease heterogeneity in ALS. It has been proposed that ALS spreads focally in the nervous system based on the somatotropic anatomy of motor neurons. This has not been shown in vivo by neuroimaging to date. Furthermore, no objective biomarkers are currently available in ALS that would sensitively correlate with disability.

Design/Methods DESIGN/METHODS: We have conducted a single-centre, single-protocol quantitative neuroimaging study of 33 cognitively normal ALS patients and 44 healthy controls. A voxelwise generalized linear model was used to investigate the distribution of disease burden within the motor cortex in relation to clinical disability. Histologically defined motor cortex masks were used to define regions of interests.

Results RESULTS: Bulbar onset patients demonstrated bilateral focal atrophy in the bulbar segment of the motor homunculus compared limb onset patients who showed focal cortical changes in the limb segment of their motor strip. Irrespective of site of onset, bulbar and upper limb scores of individual patients showed a strikingly linear association with grey matter volumes in the relevant portions of the primary motor cortex (PMC). Another PMC cluster was also identified where grey matter volume signal showed a negative linear association with disease duration. Moreover, cortical ALS pathology was identified beyond the motor cortex affecting frontal, occipital and temporal regions.

Conclusions CONCLUSIONS: Focal grey matter atrophy within the primary motor cortex corresponds with functional disability in ALS. The findings support the existing concepts of cortical focality and motor phenotype heterogeneity in ALS. Our data indicate that volumetric approaches have the potential to provide a valuable objective measure of upper motor neuron disease burden in ALS.

Authors/Disclosures
Peter Bede, MD, PhD (Academic Unit of Neurology) PRESENTER	Dr. Bede has nothing to disclose.
	No disclosure on file
Marwa Elamin, MD, PhD (University College Hospital Galway)	Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .
Susan C. Byrne, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
Orla Hardiman, MD, DSc, FRCPI, MRIA, FAAN (Trinity Biomedical Sciences Institute)	Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.
Shiv Saidha, MD (Johns Hopkins)	Dr. Saidha has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Setpoint Medical. Dr. Saidha has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReWind Therapeutics. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Pharmaceuticals. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Saidha has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal ETC. Dr. Saidha has stock in June Brain. Dr. Saidha has stock in Lapix Therapeutics. The institution of Dr. Saidha has received research support from Biogen. The institution of Dr. Saidha has received research support from Genentech. The institution of Dr. Saidha has received research support from Novartis. The institution of Dr. Saidha has received research support from Lapix Therapeutics. The institution of Dr. Saidha has received research support from Novartis.

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