Upper limb evaluation and one-year follow up of non-ambulant patients with spinal muscular atrophy: an observational multicenter trial.

A Seferian ,Nicolas Deconinck,Kim Maincent,Laurent Servais,Oumar Diebate,Virginie Jousten,Wendy Vereecke,Thomas Voït ,A Moraux ,A Canal ,Susana Quijano‐Roy ,V Decostre ,T Gidaro ,Séverine Denis ,M Annoussamy ,M Mayer ,F Van Parys ,Jean‐Marie Cuisset ,Jean‐Yves Hogrel ,S Wittevrongel ,A.g Le Moing ,V Tiffreau

doi:10.1371/journal.pone.0121799

Abstract

Assessment of the upper limb strength in non-ambulant neuromuscular patients remains challenging. Although potential outcome measures have been reported, longitudinal data demonstrating sensitivity to clinical evolution in spinal muscular atrophy patients are critically lacking. Our study recruited 23 non-ambulant patients, 16 patients (males/females = 6/10; median age 15.4 years with a range from 10.7 to 31.1 years) with spinal muscular atrophy type II and 7 patients (males/females = 2/5; median age 19.9 years with a range from 8.3 to 29.9 years) with type III. The Brooke functional score was on median 3 with a range from 2 to 6. The average total vital capacity was 46%, and seven patients required non-invasive ventilation at night. Patients were assessed at baseline, 6 months, and 1 year using the Motor Function Measure and innovative devices MyoGrip, MyoPinch, and MoviPlate, which assess handgrip strength, key pinch strength, and hand/finger extension-flexion function, respectively. The study demonstrated the feasibility and reliability of these measures for all patients, and sensitivity to negative changes after the age of 14 years. The younger patients showed an increase of the distal force in the follow-up period. The distal force measurements and function were correlated to different functional scales. These data represent an important step in the process of validating these devices as potential outcome measures for future clinical trials.Trial RegistrationClinicalTrials.gov NCT00993161

Highlights

Spinal muscular atrophy (SMA) is the second most frequent autosomal recessive disorder worldwide
The aims of our study were 1) to assess the feasibility and reliability of different strength (MyoGrip, MyoPinch) and functional (MoviPlate, motor function measure (MFM)) measures in non-ambulant patients with SMA; 2) to assess the sensitivity to change for the same measurements over one year; and 3) to determine the sample size of non-ambulant patients with SMA needed in clinical trials to prove whether a given drug effectively stabilizes the disease
Our study demonstrated that the use of sensitive dynamometers and a designed functional test is feasible for assessing the upper limbs in almost all non-ambulant SMA type II and III patients

Summary

Introduction

Spinal muscular atrophy (SMA) is the second most frequent autosomal recessive disorder worldwide. It is caused by homozygous absence of the SMN1 gene [1] and results in degeneration of the spinal motor neurons. Children with SMA II achieve the ability to sit independently but never stand or walk independently. Those with SMA III achieve the ability to stand and walk independently, but about half of the patients lose this ability before the age of 18 [5, 6]. The SMA phenotype varies within each SMA type, covering a wide range of functional abilities

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