Muscle strength and motor function in adolescents and adults with spinal muscular atrophy

Neurology ◽  
2020 ◽  
Vol 95 (14) ◽  
pp. e1988-e1998 ◽  
Author(s):  
Camiel A. Wijngaarde ◽  
Marloes Stam ◽  
Louise A.M. Otto ◽  
Bart Bartels ◽  
Fay-Lynn Asselman ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Older Patients ◽  
Muscular Atrophy ◽  
Compound Muscle Action Potential ◽  
Adult Patients ◽  
Cross Sectional ◽  
Floor Effects ◽  
Adolescents And Adults

ObjectiveTo assess longitudinal patterns of muscle strength, motor function, and maximal compound muscle action potential amplitudes (CMAPMAX) in older patients with spinal muscular atrophy (SMA), hypothesizing a continued decline of motor function parameters throughout life.MethodsWe measured muscle strength (Medical Research Council), motor function (Hammersmith Functional Motor Scale Expanded [HFMSE] and Motor Function Measure), and CMAPMAX in treatment-naive patients. We used both longitudinal and cross-sectional data in mixed models to analyze natural history patterns.ResultsWe included 250 patients with SMA types 1c through 4. Median patient age at assessment was 26.8 years, the number of assessments per patient ranged from 1 to 6. Baseline muscle strength and motor function scores differed significantly between SMA types, but annual rates of decline were largely similar and mostly linear. HFMSE floor effects were present for all patients with SMA type 1c, and adolescents and adults with types 2 and 3a. CMAPMAX differed significantly between SMA types but did not decline significantly with increasing age. Muscle strength correlated very strongly with motor function (τ ≥ 0.8) but only moderately with CMAPMAX (τ ≈ 0.5–0.6).ConclusionMuscle strength and motor function decline in older patients with SMA are constant without periods of slower progression or a plateau phase. The floor effects of the HFMSE preclude its use for long-term follow-up of adult patients with SMA types 1c through 3a. Muscle strength sum scores represent an alternative, feasible outcome measure for adolescent and adult patients with SMA.

Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4

2018 ◽  
Vol 25 (3) ◽  
pp. 512-518 ◽  
Author(s):  
R. I. Wadman ◽  
C. A. Wijngaarde ◽  
M. Stam ◽  
B. Bartels ◽  
L. A. M. Otto ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Cross Sectional

scholarly journals Nusinersen in later-onset spinal muscular atrophy

Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2492-e2506 ◽  
Author(s):  
Basil T. Darras ◽  
Claudia A. Chiriboga ◽  
Susan T. Iannaccone ◽  
Kathryn J. Swoboda ◽  
Jacqueline Montes ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Compound Muscle Action Potential ◽  
Extension Study ◽  
Type Ii ◽  
Open Label ◽  
Type Iii ◽  
Link Type ◽  
Phase 1B

ObjectiveTo report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA).MethodsAnalyses included children from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2–15 years. The extension study was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant (196–413 days). Assessments included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), 6-Minute Walk Test (6MWT), compound muscle action potential (CMAP), and quantitative multipoint incremental motor unit number estimation. Safety also was assessed.ResultsTwenty-eight children were included (SMA type II, n = 11; SMA type III, n = 17). Mean HFMSE scores, ULM scores, and 6MWT distances improved by the day 1,150 visit (HFMSE: SMA type II, +10.8 points; SMA type III, +1.8 points; ULM: SMA type II, +4.0 points; 6MWT: SMA type III, +92.0 meters). Mean CMAP values remained relatively stable. No children discontinued treatment due to adverse events.ConclusionsNusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. These results document the long-term benefit of nusinersen in later-onset SMA, including SMA type III.Clinicaltrials.gov identifierNCT01703988 (ISIS-396443-CS2); NCT02052791 (ISIS-396443-CS12).Classification of evidenceThis study provides Class IV evidence that nusinersen improves motor function in children with later-onset SMA.

Motor function-muscle strength relationship in spinal muscular atrophy

2004 ◽  
Vol 29 (4) ◽  
pp. 548-552 ◽  
Author(s):  
Luciano Merlini ◽  
Enrico Bertini ◽  
Carlo Minetti ◽  
Tiziana Mongini ◽  
Lucia Morandi ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Strength Relationship

Correlates of fatigability in patients with spinal muscular atrophy

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011230
Author(s):  
Bart Bartels ◽  
Janke F. de Groot ◽  
Laura E. Habets ◽  
Renske I. Wadman ◽  
Fay-Lynn Asselman ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Neuromuscular Junction ◽  
Spinal Muscular Atrophy ◽  
Ulnar Nerve ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Short Form ◽  
Drop Out ◽  
Cox Regression Analysis ◽  
Sum Score

ObjectiveTo determine the associations between fatigability and muscle strength, motor function, neuromuscular junction (NMJ) function and perceived fatigue in spinal muscular atrophy (SMA) we assessed 61 patient with SMA.MethodsFatigability was defined as the inability to continue a 20-minute submaximal repetitive task of either walking or proximal- or distal arm function and expressed as ‘drop-out’ on the Endurance Shuttle Test Combined Score (ESTCS). We assessed muscle strength with the MRC sum score, motor function with the Hammersmith Functional Motor Scale Expanded (HFMSE) and Motor Function Measure (MFM), NMJ-function with repetitive nerve stimulation of the accessory- and ulnar nerve and perceived fatigue with the PROMIS fatigue short form questionnaire in 61 children and adults with SMA types 2–4. We applied Cox regression analysis to explore the associations between fatigability and these factors.ResultsThe hazard of drop-out on the ESTCS decreased with respectively 0.8%, 2% and 1.3% for each point increase in the MRC sum score, the HFMSE score and the MFM percentual score. However, we observed prominent fatigability with preserved muscle function and vice versa in 13%–16% of patients. We did not find an association between neuromuscular junction dysfunction of the accessory- (p = 0.37) and ulnar nerve (p = 0.063) and fatigability, which could be due to a large number of missing values. Perceived fatigue in SMA was comparable to reference values and was not associated with fatigability (p = 0.52).ConclusionsFatigability in SMA is associated with, yet not equivalent to muscle strength and motor function.

scholarly journals Compound muscle action potential and motor function in children with spinal muscular atrophy

2010 ◽  
Vol 42 (5) ◽  
pp. 703-708 ◽  
Author(s):  
Aga Lewelt ◽  
Kristin J. Krosschell ◽  
Charles Scott ◽  
Ai Sakonju ◽  
John T. Kissel ◽  
...  
Keyword(s):  
Action Potential ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Compound Muscle Action Potential ◽  
Muscle Action ◽  
Muscle Action Potential

scholarly journals Physical Therapy for Type III Spinal Muscular Atrophy in a Uyghur Pedigree

2021 ◽  
Author(s):  
yangyang wang ◽  
Jing Ma ◽  
Chunli Li ◽  
Hai Xu ◽  
Jiejun Chi ◽  
...  
Keyword(s):  
Physical Therapy ◽  
Muscle Strength ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Exercise Program ◽  
Proximal Muscle ◽  
Training Exercise ◽  
Type Iii ◽  
Progressive Resistance

Abstract Background: Spinal muscular atrophy (SMA) is a genetically determined neuromuscular disease with predominantly proximal muscle atrophy and weakness caused by degeneration of lower motor neurons in the central nervous system. SMN1 is recognized as an SMA causing gene. The SMN2 copy numbers was assessed for SMA severity. Multiple ligation-dependent probe amplification (MLPA) technique allows to confirm the diagnosis of SMA. The clinical spectrum in affected individuals varies widely from severe generalized weakness (SMA types I and II) to modest proximal muscle weakness (SMA types III and IV). Most patients with SMA have reduced muscle strength and physical dysfunction more or less. Preliminary evidence in people with SMA and in SMA animal models suggests exercise has potential benefits in improving or stabilizing muscle strength and motor function. Physical therapy (PT) in the case with SMA type III to assess the effects.Methods: MLPA was carried out in a family with maternal consanguineous marriage. We evaluated feasibility, safety, and effects on strength and motor function of a supervised progressive resistance strength training exercise program in the children with SMA types III.Results: A SMA III pedigree from the Uyghur population was found a homozygous deletion of SMN1 exon 7 and exon 8. Numbers of SMN2 were 4 copies in them. The proband’s son is well tolerated to physical training. PT training is benefical to his physical function and yet improvement in fatigue and muscle strength gets limited.Conclusions: A two sessions supervised, 3 days/week progressive resistance training exercise program is feasible, safe, and well tolerated in children with SMA III.

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