Upper limb strength and function changes during a one-year follow-up in non-ambulant patients with Duchenne Muscular Dystrophy: an observational multicenter trial.

INTRODUCTION: Upper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluations of efficacy of new treatments in non-ambulant patients. In patients who have lost ambulation, there are few validated and informative outcome measures. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures over short-term periods are lacking. PATIENTS AND METHODS: We report here the results of a one-year multicenter study using specifically designed tools to assess grip, pinch strength, and hand function in wheelchair-bound patients. Our study assessed 53 non-ambulant patients with Duchenne muscular dystrophy aged 17.1 ± 4.8 years (range: 9 - 28.1 years). The average Brooke functional score of these patients was 4.6 ± 1.1. The average forced vital capacity was 44.5% predicted and 19 patients used non-invasive ventilation. Patients were assessed at baseline, 6 months, and one year using the Motor Function Measure and innovative devices (namely the MyoSet composed of MyoGrip, MyoPinch, and MoviPlate). RESULTS: Our study confirmed preliminary data previously reported regarding feasibility of use and of reliability of the MyoSet and the correlation at baseline between distal strength and clinical outcomes such as FVC, Brooke score, age, and duration since loss of ambulation. A significant correlation was observed between the distal upper limb strength and clinical variables. The sensitive dynamometers (MyoGrip and MyoPinch) and MoviPlate captured a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages. TRIAL REGISTRATION: ClinicalTrials.gov NCT00993161 NCT00993161.

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

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.

Improving the selectivity of the phosphoric acid ß-elimination on a biotinylated phosphopeptide.

This study aims at improving the MALDI-TOF detection of a phosphorylated peptide containing a cysteine residue by ß-elimination of H(3)PO(4) hardly enriched by classical methods. The experimental conditions were optimized on this phosphopeptide (biot-pAdd) and its nonphosphorylated counterpart (biot-Add). The major side-reactions were H(2)S elimination on the cysteine residues and H(2)O elimination on the non phosphorylated serine residue of biot-Add. The former dilutes the MALDI-TOF signal for the desired species. The latter gives a product similar to what is obtained by H(3)PO(4) elimination and should prompt to caution when working with a mixture between phosphorylated and non phosphorylated peptides. Modifications on the solvent, the reaction temperature and time, the nature, and concentration of the base were made. Major improvement of the selectivity of the reaction was observed in 30 % ACN, at room temperature for 4 h. However, these optimizations are specific to these sequences and should be performed anew for different peptides. The selectivity of the reaction towards H(3)PO(4) elimination is improved, but the persistence of side-reactions renders a previous sample fractionation necessary. In these optimized conditions, the ionization enhancement is 3-fold and the detection limits for biot-pAdd are similar to biot-Add (100 fmol).