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Abstract Details

Medullary Lesions as a Specific Neuropathological Basis for Sleep Disturbance in Early Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis
S49 - Multiple Sclerosis: Basic Science (2:12 PM-2:24 PM)
007

To characterize risk of sleep disturbance in young adults with early relapsing-remitting multiple sclerosis (MS) and very low disability, and identify specific patterns of disease-related inflammatory or neurodegenerative changes associated with disturbed sleep.
Persons with MS often report sleep disturbance, which has historically been attributed to disease-related spasticity, bladder dysfunction, or mood symptoms. It is unknown whether specific pathophysiological features of MS disrupt sleep independently of symptoms. Previous research on sleep in MS has utilized heterogeneous samples with wide-ranging disease durations and levels of disability, making it challenging to identify specific independent neural bases.
The RADIEMS cohort of early RRMS patients (n=185; ≤5.0 years diagnosed; EDSS median=1.0, IQR: 0.0-1.5; aged 34.4±7.5 years; 123 women) completed the Insomnia Severity Index (ISI) to characterize rates of sleep disturbance (ISI≥10) relative to 425 demographically-similar healthy controls (aged 34.0±7.7 years; 284 women). Multimodal 3T MRI investigated links between sleep disturbance in patients and measures of global and regional gray matter, integrity of normal-appearing white matter, global and regional T2 lesions volumes, and brainstem lesions within the midbrain, pons, and medulla. Investigation of brainstem lesions was informed by research on sleep circuitry in non-human mammals.
Sleep disturbance was more common in patients (40.5%, 75/185) than controls (27.1%, 115/425; p=.001), even when controlling for age, sex, mood, and BMI (p=.004).  Presence of medullary lesion(s) was the only independent predictor of sleep disturbance, was robust against control for potential confounders (i.e., mood, physical symptoms), and withstood multiple comparisons corrections. Most patients with medullary lesion(s) reported sleep disturbance (66.0%, 31/47), which was much greater than in controls (27.1%, 115/425, p<.001) and patients without medullary lesions (31.6%, 43/136, p<.001).
Findings suggest a role for disease-related brainstem pathophysiology in disrupting sleep independently of physical or mood symptoms in young adults with early RRMS, which may inform future treatments.
Authors/Disclosures
James F. Sumowski (Icahn School of Medicine At Mount Sinai)
PRESENTER 		Mr. Sumowski has nothing to disclose.
Andrew W. Varga, MD No disclosure on file
Stephen Krieger, MD, FAAN (Mount Sinai Dept of Neurology) Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Expert Witness. The institution of Dr. Krieger has received research support from Novartis. The institution of Dr. Krieger has received research support from Bristol Myers Squibb. The institution of Dr. Krieger has received research support from Biogen.
Rachel Brandstadter, MD (University of Pennsylvania) Dr. Brandstadter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion.
Ilana B. Katz Sand, MD (Corinne Goldsmith Dickinson Center for MS) The institution of Dr. Katz Sand has received research support from National Multiple Sclerosis Society. The institution of Dr. Katz Sand has received research support from Hirschl Foundation. The institution of Dr. Katz Sand has received research support from National Institutes of Health. Dr. Katz Sand has received personal compensation in the range of $500-$4,999 for serving as a Conference presenter with 好色先生.
Victoria Leavitt, PhD, FAAN (Columbia University Irving Medical Center) Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Leavitt has received research support from National Institutes of Health. The institution of Dr. Leavitt has received research support from National Multiple Sclerosis Society. The institution of Dr. Leavitt has received research support from Department of Defense. Dr. Leavitt has received intellectual property interests from a discovery or technology relating to health care.
Michelle Fabian, MD, FAAN (Mount Sinai Hospital) Dr. Fabian has nothing to disclose.
Korhan Buyukturkoglu, PhD (Columbia University) Dr. Buyukturkoglu has nothing to disclose.
Claire Riley, MD, FAAN (Columbia University Medical Center) Dr. Riley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Riley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Riley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Riley has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Riley 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. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. Dr. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cabaletta Bio. Dr. Riley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb.
Sylvia Klineova, MD (Icahn School of Medicine At Mount Sinai) Dr. Klineova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Klineova has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Klineova has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Klineova has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Fred D. Lublin, MD, FAAN (Icahn School of Medicine At Mount Sinai) Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche/Genentech. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medimmune/Viela Bio/Horizon. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Receptos/Celgene/BMS. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Labcorp. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuralight. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Entelexo. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Lublin has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Multiple entities. Dr. Lublin has stock in Avotres. Dr. Lublin has stock in Neuralight. The institution of Dr. Lublin has received research support from Brainstorm. The institution of Dr. Lublin has received research support from biogen. The institution of Dr. Lublin has received research support from NIH.
Aaron E. Miller, MD, FAAN (Mt Sinai School Of Med) Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Accordant Health Services (Caremark). Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Corevitas (formerly known as Corrona). Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MAPI=Pharma. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Viatris (Mylan). Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen (Horizon Therapeutics). Dr. Miller has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Sterne Kessler. Dr. Miller has received publishing royalties from a publication relating to health care.
Sam H. Horng, MD, PhD The institution of Dr. Horng has received research support from National Institutes of Health . The institution of Dr. Horng has received research support from Jayne and Harvey Beker Foundation .