Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals With Ankle Dorsiflexors' Disparity in Strength.

OBJECTIVE: To compare effects of contralateral strength training (CST) and direct strength training of the more affected ankle dorsiflexors on muscle performance and clinical functional outcomes in people with multiple sclerosis (MS) exhibiting interlimb strength asymmetry. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: Individuals with relapsing-remitting MS (N=30) and mild-to-moderate disability (Expanded Disability Status Scale score ≤6) presenting with ankle dorsiflexors' strength disparity. INTERVENTIONS: Participants were randomly assigned to a CST (n=15) or direct strength training (n=15) group performing 6 weeks of maximal intensity strength training of the less or more affected dorsiflexors, respectively. MAIN OUTCOME MEASURES: Maximal strength, endurance to fatigue, and mobility outcomes were assessed before, at the intervention end, and at 12-week follow-up. Strength and fatigue parameters were measured after 3 weeks of training (midintervention). RESULTS: In the more affected limb of both groups, pre- to postintervention significant increases in maximal strength (P≤.006) and fatigue endurance (P≤.04) were detected along with consistent retention of these improvements at follow-up (P≤.04). At midintervention, the direct strength training group showed significant improvements (P≤.002), with no further increase at postintervention, despite training continuation. Conversely, the CST group showed nonsignificant strength gains, increasing to significance at postintervention (P≤.003). In both groups, significant pre- to postintervention improvements in mobility outcomes (P≤.03), not retained at follow-up, were observed. CONCLUSIONS: After 6 weeks of training, CST proved as effective as direct strength training in enhancing performance of the more affected limb with a different time course, which may have practical implications in management of severely weakened limbs where direct strength training is not initially possible.

Effect of Contralateral Strength Training on Muscle Weakness in People With Multiple Sclerosis: Proof-of-Concept Case Series.

BACKGROUND: The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side. OBJECTIVE: The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb. DESIGN: A single-subject research design was used. METHODS: Eight individuals with MS underwent 16 to 18 high-intensity training sessions of the less-affected ankle dorsiflexor muscles. The primary outcome measure of this single-system case series was maximal strength expressed as peak moment and maximal work. Secondary outcome measures were: Six-Minute-Walk Test, Timed "Up & Go" Test, 10-Meter Timed Walk Test, and Multiple Sclerosis Quality of Life-54 questionnaire. RESULTS: After the 6-week intervention, the contralateral more affected (untrained) limb showed a 22% to 24% increase in maximal strength. From pretest-posttest measurements, participants also performed significantly better on the clinical and functional secondary outcome measures. At the 12-week follow-up, the strength levels of the weaker untrained limb remained significantly superior to baseline levels in the majority (5 out of 8) of the outcome parameters. LIMITATIONS: Considering the design used, the absence of a control group, and the sample size, these findings should be cautiously generalized and will need confirmation in a properly planned randomized controlled trial. CONCLUSIONS: The present proof-of-concept study shows, for the first time, the occurrence of the CST effect on muscle performance of ankle dorsiflexor muscles in people with MS. These preliminary findings reveal new potential implications for CST as a promising rehabilitation approach to those conditions where unilateral muscle weakness does not allow or makes difficult performing conventional strength training of the weaker limb.

Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis.

Ectopic periarticular calcifications associated with elevated levels of serum phosphate represent the principal clinical features of hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive metabolic disorder. The disease can be caused by recessive mutations in at least two different genes: GalNAc transferase 3 (GALNT3), encoding a glycosyltransferase that initiates mucin-type O-glycosylation, and fibroblast growth factor 23 (FGF23), which encodes a regulator of phosphate circulating levels. In the current study, we performed mutation analyses of the GALNT3 gene in a subject with HFTC and in his relatives. Sequence analyses revealed that the proband was a compound heterozygote for two novel nonsense mutations in exon 4 (Y322X) and in exon 7 (Q481X). Cosegregation of the mutations with the disease within the family was confirmed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. This is the first report describing the simultaneous presence of two different stop codons in the coding sequence of the GALNT3 gene.