Rafael Rodriguez-Torres1, Julia Fabiano1, Ashley Goodwin1, Ashwini K Rao1,2, Stacy Kinirons1, Darryl De Vivo3, Jacqueline Montes1,3. 1. Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, NY, USA. 2. G.H. Sergievsky Center, Columbia University Irving Medical Center, New York, NY, USA. 3. Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Abstract
BACKGROUND: Individuals with spinal muscular atrophy (SMA) III walk independently, but experience muscle weakness, gait impairments, and fatigue. Although SMA affects proximal more than distal muscles, the characteristic pattern of selective muscle weakness has not been explained. Two theories have been proposed: 1) location of spinal motor neurons; and 2) differences in segmental innervation. OBJECTIVE: To identify neuroanatomical models that explain the selective muscle weakness in individuals with SMA and assess the relationship of these models to ambulatory function. METHODS: Data from 23 ambulatory SMA participants (78.2% male), ages 10-56 years, enrolled in two clinical studies (NCT01166022, NCT02895789) were included. Strength was assessed using the Medical Research Council (MRC) score; ambulatory function was measured by distance walked on the 6-minute walk test (6 MWT). Three models were identified, and relationships assessed using Pearson correlation coefficients and linear regression. RESULTS: All models demonstrated a positive association between strength and function, (p < 0.02). Linear regression revealed that Model 3B, consisting of muscles innervated by lower lumbar and sacral segments, explained 67% of the variability observed in 6 MWT performance (β= 0.670, p = 0.003). CONCLUSIONS: Muscles innervated by lower lumbar and sacral segments, i.e. hip extensors, hip abductors, knee flexors and ankle dorsiflexors, correlated with and predicted greater ambulatory function. The neuroanatomical patterns of muscle weakness may contribute to a better understanding of disease mechanisms and enable delivery of targeted therapies.
BACKGROUND: Individuals with spinal muscular atrophy (SMA) III walk independently, but experience muscle weakness, gait impairments, and fatigue. Although SMA affects proximal more than distal muscles, the characteristic pattern of selective muscle weakness has not been explained. Two theories have been proposed: 1) location of spinal motor neurons; and 2) differences in segmental innervation. OBJECTIVE: To identify neuroanatomical models that explain the selective muscle weakness in individuals with SMA and assess the relationship of these models to ambulatory function. METHODS: Data from 23 ambulatory SMA participants (78.2% male), ages 10-56 years, enrolled in two clinical studies (NCT01166022, NCT02895789) were included. Strength was assessed using the Medical Research Council (MRC) score; ambulatory function was measured by distance walked on the 6-minute walk test (6 MWT). Three models were identified, and relationships assessed using Pearson correlation coefficients and linear regression. RESULTS: All models demonstrated a positive association between strength and function, (p < 0.02). Linear regression revealed that Model 3B, consisting of muscles innervated by lower lumbar and sacral segments, explained 67% of the variability observed in 6 MWT performance (β= 0.670, p = 0.003). CONCLUSIONS: Muscles innervated by lower lumbar and sacral segments, i.e. hip extensors, hip abductors, knee flexors and ankle dorsiflexors, correlated with and predicted greater ambulatory function. The neuroanatomical patterns of muscle weakness may contribute to a better understanding of disease mechanisms and enable delivery of targeted therapies.
Entities:
Keywords:
Spinal muscular atrophy; muscle weakness; strength; walk test; walking
Authors: Eugenio Mercuri; Richard S Finkel; Francesco Muntoni; Brunhilde Wirth; Jacqueline Montes; Marion Main; Elena S Mazzone; Michael Vitale; Brian Snyder; Susana Quijano-Roy; Enrico Bertini; Rebecca Hurst Davis; Oscar H Meyer; Anita K Simonds; Mary K Schroth; Robert J Graham; Janbernd Kirschner; Susan T Iannaccone; Thomas O Crawford; Simon Woods; Ying Qian; Thomas Sejersen Journal: Neuromuscul Disord Date: 2017-11-23 Impact factor: 4.296
Authors: Jeong-Ki Kim; Narendra N Jha; Zhihua Feng; Michelle R Faleiro; Claudia A Chiriboga; Lan Wei-Lapierre; Robert T Dirksen; Chien-Ping Ko; Umrao R Monani Journal: J Clin Invest Date: 2020-03-02 Impact factor: 14.808
Authors: Niko Hensel; Inga Stockbrügger; Sebastian Rademacher; Natasha Broughton; Hella Brinkmann; Claudia Grothe; Peter Claus Journal: Cell Signal Date: 2013-12-03 Impact factor: 4.315
Authors: Lyndsay M Murray; Laura H Comley; Derek Thomson; Nick Parkinson; Kevin Talbot; Thomas H Gillingwater Journal: Hum Mol Genet Date: 2007-12-08 Impact factor: 6.150