Abstract Details

Title The anatomical substrate of bulbar impairment in ALS: insights from multiparametric brainstem imaging, corticobulbar connectivity and somatotopic motor cortex measures

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-004

Objective The comprehensive characterisation of the natural history of ALS-associated brainstem, corticobulbar, motor cortex and cerebellar pathology and their contribution to progressive bulbar impairment.

Background Bulbar impairment is a hallmark feature of ALS with considerable quality of life implications, nutritional and communication ramifications, which require carefully-timed multidisciplinary interventions. In sharp contrast to the robust post mortem literature, the characterisation of brain stem pathology in vivo has been limited in ALS to date.

Design/Methods A large, prospective, longitudinal neuroimaging study has been undertaken with 100 ALS patients, 20 PLS patients, 40 disease-controls with neurodegenerative conditions and 100 healthy controls. ALS patients were scanned every 6-8 months. Standardised clinical, functional, and genetic evaluation was carried out and patients were also assessed for pseudobulbar affect. Three Tesla neuroimaging included high resolution structural, functional and diffusion sequences and imaging analyses focused on multiparametric measures of brain stem integrity, corticobulbar connectivity, motor cortex indices and cerebellar measures. Descriptive analyses were performed in anatomical regions associated with bulbar function exploring the pathological substrate of both lower and upper motor neuron dysfunction. Group comparisons were adjusted for demographic factors and total intracranial volumes where appropriate.

Results Irrespective of bulbar impairment, ALS patients exhibit progressive brainstem atrophy and vertex alterations in comparison to healthy- and disease controls. Corticobulbar tract degeneration can be readily detected in the majority of ALS and PLS patients, but functional disability is primarily driven by lower motor neuron degeneration. Upper motor neuron type bulbar disability is associated with the selective degeneration of white matter fibres in the internal capsule and somatotopic grey matter alterations in the motor cortex.

Conclusions Multiparametric brainstem and corticobulbar imaging provides unprecedented insights into the natural history of bulbar impairment in ALS offering unique diagnostic, monitoring and prognostic opportunities both for clinical trials and individualised patient care.

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
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.

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