Abstract Details

Title Glymphatic Dysfunction in Clinical Phenotypes of Motor Neuron Disease

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - Updates on Amyotrophic Lateral Sclerosis (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background Converging evidence supports a key pathogenic role of the glymphatic system in the accumulation of pathological aggregates in several proteinopathies, including amyotrophic lateral sclerosis (ALS) and other MNDs.

Objective To verify the presence of glymphatic function impairment, as shown by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), and to explore its clinical correlates in motor neuron disease (MND) phenotypes.

Design/Methods Fifty-seven patients with MND phenotypes (including 41 ALS, 7 with pure lower motor neuron and 9 with pure upper motor neuron clinical presentations) and 32 age- and sex-matched healthy controls underwent a brain MRI protocol including DTI sequences on a 3 Tesla scanner. We obtained DTI-ALPS index from each individual, evaluating its relationship with measures of motor and cognitive disability, site of symptom onset, cognitive status and fractional anisotropy (FA) values of the white matter tracts. Comparisons between groups were evaluated using ANCOVA models, age- and sex-adjusted. Partial correlations with clinical and cognitive measures were also tested.

Results Compared with healthy controls, MND patients showed significantly decreased DTI-ALPS index values (p<0.001). MND patients with a bulbar onset of symptoms showed greater reduction of DTI-ALPS index values, as compared with individuals with a spinal onset (p=0.005). Similar DTI-ALPS values were found across all MND phenotypes, with no effect of cognitive diagnosis or C9orf72 expansion status. Significant correlations were found between DTI-ALPS and disease duration (r=-0.30, p=0.03) and FA values of the anterior corona radiata (r=0.31, p=0.02) and body of the corpus callosum (r=0.37, p=0.049).

Conclusions In this study, we confirm the presence of altered glymphatic function across MND phenotypes, with greatest damage in patients with a bulbar symptom onset. Our findings support a pathogenic involvement of this system for the accumulation of TDP-43 proteinopathy in MND.

Authors/Disclosures
Ilaria Bottale, MD PRESENTER	Dr. Bottale has nothing to disclose.
Edoardo G. Spinelli, MD	Dr. Spinelli has nothing to disclose.
Silvia Basaia	Silvia Basaia has nothing to disclose.
Alma Ghirelli	No disclosure on file
Francesca Orlandi	No disclosure on file
Tommaso Russo, MD (MassGeneral Institute for Neurodegenerative Diseases)	Dr. Russo has nothing to disclose.
Elisa Canu (Ospedale San Raffaele)	The institution of Elisa Canu has received research support from Italian Ministry of Health .
Veronica Castelnovo, MSc (San Raffaele Scientific Institute, Vita-Salute San Raffaele University)	Dr. Castelnovo has nothing to disclose.
Paride Schito	Paride Schito has nothing to disclose.
Yuri Falzone	Yuri Falzone has nothing to disclose.
Federica Agosta (San Raffaele Scientific Institute)	Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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