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Table 2 Management approaches commonly used for adults with SMA

From: Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

Clinical IssueAssessments and monitoringManagement and sources of evidenceLevel of evidenceaContext for clinical implementationReferences
Rehabilitation
 Muscle weakness limiting mobility, function and activities of daily livingOptimal methods for evaluation and monitoring for adults are lackingAssistive devices
Consensus statements and surveys describing use of orthoses and assistive devices
Level VLimited evidence for selection of optimal assistive devices[3, 27, 60, 66]
  Qualitative studies incorporating patient experienceUnclear – patient reported benefits[67,68,69,70]
  Case reports of development and trial of upper limb assistive exoskeletonsLevel V[63, 64]
  Pilot study of a brain computer interfaceLevel V[62]
  Case report of ocular movement detector system to aid communication in severe SMALevel V[65]
  Exercise
Single randomised controlled trial in ambulatory SMA of 14 patients – no change in 6MWT, fatigue or function, improvement in V02max.
Level IIIFurther evidence is needed to develop exercise guidelines[71]
  Open label study in 6 SMA III patients – training improves oxidative capacity, induces fatigueLevel IV[72]
Respiratory Care
 Impaired cough and ability to clear airway sectionsEvaluate cough effectivenessReviews and consensus statements outlining methods for airway clearance; case series of NIV, manually assisted coughing, MI-ELevel IVEvidence supporting optimal methods for evaluation and management are lacking[1, 59, 73]
 Respiratory muscle weaknessMonitor gas exchange for evidence of hypoventilationRespiratory support for chronic ventilatory insufficiency:
Non- invasive ventilation
Consensus statements, surveys, observational study and case reports describing use of non-invasive ventilation
Level V[1, 17, 59, 60, 74,75,76]
  Invasive ventilation
Case studies and surveys describing use of invasive ventilation in a small number of adults
Level IVInvasive ventilation when NIV is insufficient is an individual decision incorporating views of person and quality of life[77]
[60]
 Recurrent respiratory infections Immunizations
Consensus statements
Level V [1, 59]
Gastrointestinal and Nutritional Care
 Feeding and swallowing difficulties associated with lower body weight and increased risk of aspiration pneumoniaSpeech therapist and dietitian evaluation of feeding, swallowing and nutritionReviews and consensus statements describe modifying food consistency, optimizing oral intake, enhance feeding with positioning, seating and equipment
Gastrostomy to provide nutritional supplementation when oral intake inadequate
Level VNo evidence to support specific diets.
No consensus on when to commence enteral supplementation: an individual decision incorporating views of person and quality of life
[3]
  Surveys and case reports describing frequency and management of feeding difficulties in adult SMALevel IV[78, 79] [52]
 Gastrointestinal dysmotility (reflux, constipation and delayed gastric emptying) Consensus statements suggests gastroesophageal reflux medications, prokinetic agents, aperients, nissen fundoplicationLevel V[3]
Disease modifying medication
AgentStudy designResultsLevel of evidenceaContext for clinical implementationReferences
 ValproateProspective randomized placebo controlled cross-over trial of 33 ambulatory adults with SMANo change in max voluntary isometric contraction, pulmonary, electrophysiological, or functional outcomesLevel IValproate is well tolerated, no improvement in strength or function in adults with SMA[80]
 Open label, 6 adults with SMA II and III
Retrospective open label, 7 adults with SMA III and IV, mean duration 8 months
No change in motor function, variable changes in pulmonary outcomes
Increased quantitative muscle strength and subjective function
Level V
Level V
 [81]
[82]
 GabapentinRandomized controlled vs no treatment in 120 adults with SMA II and III over 12 monthsImprovement in leg muscle strength at 12 months; no change in functional tests or FVC.Level IVInconsistent evidence of efficacy[83]
 Randomized double blind placebo controlled trial in 84 adults with SMA II and IIINo differences between placebo and drug in strength, FVC, functional rating scale, impact profileLevel I [84]
 HydroxyureaRandomized, double-blind, placebo controlled trial – 55 SMA II and SMA III patients (aged 5–41)No improvements in motor or respiratory function, increased development of neutropenia in the hydroxyurea groupLevel INo evidence of efficacy[85]
 SalbutamolRandomized, double-blind, placebo-controlled trial – 45 SMA III (aged 21–53 years), 12 months duration
Open label, 10 patients (aged 28–61 years), 12–72 months of salbutamol treatment
Safe and well tolerated. Significant and progressive increase in blood SMN2 full length protein in peripheral blood in salbutamol treated patients.
Patients reported benefits of decreased fatigue, improved functioning, infrequent side effects
Level II
Level IV
Underpowered to demonstrate clinical efficacy
Unclear – patient reported benefits
[86]
[87]
NusinersenProspective open label observational study, 19 SMA III (aged 18–59 years), 10 months duration
Retrospective open label case series, 4 adults SMA III (aged 19–52 years), follow up 4–20 months
Descriptive studies of repeated intrathecal nusinersen administration in adolescent and adult patients – 78 patients in total (aged 11–61 years)
Statistically significant change in 6MWT (mean improvement 8.25 m), RULM and peak cough flow with negligible effect size. Well tolerated, adverse events of back pain in 7 and post lumbar puncture headache in 4 patients.
Stable RULM, subjective improvement in endurance, hand strength, bulbar functioning
Adverse events: headache, back pain
CT guidance an option for administration using transforaminal or interlaminar approaches +/− laminotomy. Lumbar punctures were mostly well tolerated; adverse events included post lumbar headache and subarachnoid haemorrhage in 1 patient.
Level III
Level IV
Level IV
Mild treatment effect in adults with chronic SMA
Available outcome measures not adequate to capture meaningful subjective improvements
Feasibility and safety of intrathecal treatment with nusinersen demonstrated in adolescent adult patients with SMA II and III. Treatment can be medically and logistically challenging due to the clinical features of SMA.
[88]
[89]
[90,91,92,93,94,95]
  1. a Level of evidence according to the Oxford Centre for Evidence-based Medicine: Level I - Properly powered and conducted randomised clinical trial; systematic review with meta-analysis, Level II - Well-designed controlled trial without randomization; prospective comparative cohort trial, Level III - Case-control studies, retrospective cohort study, Level IV - case series with or without intervention; cross-sectional study, Level V - Opinion of respected authorities; case reports
  2. Abbreviations: MI-E Mechanical insufflation-exsufflation, FVC Forced vital capacity, VO2Max Maximal oxygen uptake;