Abstract Details

Title Characterising Progressive Brainstem Pathology in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis: In Vivo Insights Based on Computational Imaging

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S46 - Neuromuscular and Clinical Neurophysiology (EMG): Motor Neuron/Charcot Marie Tooth (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Background Brainstem pathology is a pathognomonic feature of ALS. The medulla oblongata contains lower cranial nerve nuclei and the descending pyramidal tracts which are hallmark grey and white matter components of ALS-associated neurodegeneration. Due to the small size of the structure and segmentation difficulties, most imaging studies in ALS focus on cortical and internal capsule pathology instead of the quantitative characterisation of brainstem degeneration.

Objective The longitudinal characterisation of medulla oblongata, pons and mesencephalon degeneration in ALS and PLS.

Design/Methods 100 ALS patients, 33 PLS patients, 30 FTD patients and 100 healthy controls were included in a prospective imaging study. Each ALS patient was scanned three times longitudinally. Volumetric, vertex, morphometric and white matter analyses were conducted to characterise disease-specific patterns of brainstem pathology. The brainstem was segmented into the medulla, pons and mesencephalon using a Bayesian segmentation algorithm to measure regional volume reductions. Vertex analyses were performed to characterise the atrophy profile of each study-group and morphometry was used to evaluate focal density reductions. Tract-based white matter analyses were undertaken to evaluate diffusivity alterations in the corticospinal and corticobulbar tracts.

Results Progressive volume reductions in ALS and PLS are dominated by medulla oblongata atrophy, but pontine pathology can also be detected. In ALS, vertex analyses confirm the flattening of the medullary pyramids bilaterally in comparison to healthy and disease controls. The ALS group exhibit bilateral density reductions in the mesencephalic crura and central pons, as well as increased RD and decreased FA in the descending pyramidal tracts.

Conclusions Brainstem imaging captures progressive white and grey matter degeneration in ALS. Our clinical correlations and longitudinal data highlight the biomarker potential of quantitative brainstem measures in ALS. At a time when a multitude of pharmaceutical trials are underway worldwide, there is an unprecedented need for accurate biomarkers to monitor disease progression and detect response to therapy.

Authors/Disclosures
Peter Bede, MD, PhD (Academic Unit of Neurology) PRESENTER	Dr. Bede has nothing to disclose.
Ibrahim Laleka	No disclosure on file
Eoin Finegan, MBBS	Dr. Finegan has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Siobhan Hutchinson, MD (St. James'S Hospital)	Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Teva.
Colette G. Donaghy, MD (Royal Victoria Hospital Belfast)	Colette G. Donaghy, MC MRCP has nothing to disclose.
	No disclosure on file
Orla Hardiman, MD, FRCPI, 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.

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