Abstract Details

Title The Clinical and Neuroimaging Features of Primary Lateral Sclerosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S54 - Motor Neuron Disease (3:41 PM-3:52 PM)

Poster/Presentation
Number 002

Background PLS is a progressive, idiopathic upper motor neuron disorder associated with markedly longer survival than ALS. The protracted diagnostic journey and uncertainty about progression to ALS causes considerable distress in suspected PLS cases. There is a striking paucity of PLS clinical trials, limited understanding of genetic susceptibility and few prospective academic studies compared to other neurodegenerative conditions.

Objective To characterise the distinguishing clinical, genetic and multiparametric neuroimaging features of primary lateral sclerosis compared to ALS, neurodegenerative controls and healthy control cohorts.

Design/Methods A large, prospective, longitudinal PLS neuroimaging study was conducted, with 33 consecutive PLS patients, 50 ALS patients, 25 UMN-predominant ALS patients, 40 neurodegenerative disease-controls and 50 healthy controls. Standardised neurological evaluation, functional rating scales, UMN-burden scores, finger/foot tapping rates, cognitive assessment, pseudobulbar affect was recorded and 3 Tesla high-resolution structural, functional and diffusion tensor imaging was performed to identify PLS-specific imaging signatures. PLS subjects also underwent whole-exome sequencing.

Results

96.9% of PLS patients reported lower limb symptom onset with an ascending and symmetric propagation pattern. Functional scores and UMN burden indices highlighted lower limb predominant symptom burden, and relatively limited bulbar and respiratory involvement. One third of the patients showed evidence of cognitive impairment, mostly in language domains (25%). Pseudobulbar affect was present in 40.6% and was associated with bulbar impairment. Strikingly focal imaging signatures were identified in the PLS group with considerable precentral gyrus atrophy dominated by bilateral medial alterations in the motor homunculus. Extra-motor involvement was limited to small left mesial temporal and left inferior frontal foci. White matter analyses identified bilateral corticospinal tract degeneration highlighted by decreased fractional anisotropy, increased radial and axial diffusivity in the posterior limb of the internal capsule.

Conclusions Multiparametric imaging of clinically well-characterised PLS patients highlights remarkably focal grey and white matter pathology consistent with the patients’ clinical profile.

Authors/Disclosures
Eoin Finegan, MBBS PRESENTER	Dr. Finegan has nothing to disclose.
Ibrahim Laleka	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Colette G. Donaghy, MD (Royal Victoria Hospital Belfast)	Colette G. Donaghy, MC MRCP has nothing to disclose.
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.
Peter Bede, MD, PhD (Academic Unit of Neurology)	Dr. Bede has nothing to disclose.

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