Abstract Details

Title Weakness Is Independent of Fatigue in Diverse Neuromuscular Diseases

Topic Anterior Horn

Presentation(s) IN1 - (-)

Poster/Presentation
Number 008

Objective

Background The 6MWT is a primary end-point in many clinical trials involving neuromuscular disease. Weakness and fatigue are captured by the 6MWT, but it's uncertain whether fatigue accompanies weakness in these conditions. Comparison across neuromuscular diseases has not been examined.

Design/Methods Sixty-seven patients performed the 6MWT: (SMA =19; DMD/BMD =23; myasthenia gravis (MG) =12; mitochondrial disease (MITO) =13), ranging in age from 5 to 45 years. SMA and DMD patients were tested longitudinally. Percent-predicted distance was computed from normative values to determine weakness. Fatigue was determined by the decrement in distance from the first to sixth minute. Pearson correlation coefficients examined the relationship between percent-predicted distance and fatigue. Paired sample t-tests evaluated fatigue and distance.

Results Weakness was seen across all groups (%-predicted distance =62.2%). Fatigue was seen only in SMA (21.3% decrement), with other groups showing little or no fatigue (DMD/BMD =6.0%; MG =3.8%; MITO =0.7%). Correlation between %-predicted distance and fatigue was high only in SMA (R = - 0.73; p < 0.001). Longitudinally, %-predicted distance was constant from baseline (51.4%) to month 12 (50.6%) in SMA, whereas in DMD, %-predicted distance declined over 12 (7.1%) and 24 months (13.5%), with minimal fatigue. In the SMA group, fatigue increased significantly from 15.6% at baseline to 25.2% at 12 months (p =0.042).

Conclusions All patients with neuromuscular disease demonstrated weakness (%-predicted distance). Only the SMA group demonstrated fatigue, inversely related to walking ability. In contrast, weakness progressed in DMD without fatigue. Previous studies showed that functional worsening in SMA is absent over 12 months and only subtle over longer periods. Conversely, fatigue increased significantly over 12 months. These findings suggest independent mechanisms underlying weakness and fatigue in SMA.

Authors/Disclosures
PRESENTER	No disclosure on file
Jacqueline Montes, PT, EdD, NCS (Columbia University Medical Center)	Ms. Montes has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffman LaRoche. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. The institution of Ms. Montes has received research support from NIH/NICHD. The institution of Ms. Montes has received research support from Muscular Dystrophy Association. The institution of Ms. Montes has received research support from Cure SMA.
Sally Dunaway, DPT (Stanford University)	Dr. Dunaway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Dunaway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche/Genentech. Dr. Dunaway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Scholar Rock. Dr. Dunaway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cure SMA. The institution of Dr. Dunaway has received research support from Cure SMA. The institution of Dr. Dunaway has received research support from Scholar Rock. The institution of Dr. Dunaway has received research support from Ionis Pharmaceuticals.
Ashwini K. Rao (Rehabilitation Medicine)	No disclosure on file
Claudia A. Chiriboga, MD, FAAN (Columbia University)	Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentec. Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Chiriboga has received research support from Roche. The institution of Dr. Chiriboga has received research support from Avexis/Novartis. The institution of Dr. Chiriboga has received research support from Biogen. The institution of Dr. Chiriboga has received research support from NIH. The institution of Dr. Chiriboga has received research support from Biohaven. The institution of Dr. Chiriboga has received research support from Genentec. Dr. Chiriboga has received publishing royalties from a publication relating to health care.
Brett M. Kissela, MD, MS, FAAN (University of Cincinnati Hospital)	The institution of Dr. Kissela has received research support from NIH/NINDS.
Douglas M. Sproule, MD (MLBioSolutions)	Dr. Sproule has received personal compensation for serving as an employee of Bridge Bio. Dr. Sproule has received personal compensation for serving as an employee of Novartis, Inc. Dr. Sproule has received stock or an ownership interest from Bridge Bio.
Darryl C. De Vivo, MD, FAAN (Columbia University)	Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen and Novartis. Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspa Therapeutics.

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