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Table 1 Studies providing insights into natural history of adult SMA*

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

SourceStudy designPopulation (SMA typea, ageb, number)Primary outcome measureKey findingsQUALSYST Score
Zerres et al., 1997 [29]Multicentre retrospective studySMA types II-III, n = 569Survival probability, ambulatory probabilitySurvival rate for SMA II 68.5% at 25 years; SMA III not significantly different to normal population. Probability of ambulation at 40 years after onset 22% (SMA IIIa) and 58.7% (SMA IIIb)0.86
Zerres & Rudnik-Schӧneborn, 1995 [30]Multicentre, retrospective studySMA type I-IV, n = 445 (197 SMA type I; 104 SMA II; 73 SMA IIIa; 61 SMA IIIb; 10 SMA IV)Survival probability (types I and II), ambulatory probability (type III)Survival probability at 20 years of age: 0 and 77% for type I and II respectively. Ambulatory probabilities at 40 years of age: 45 and 67% for type IIIa and IIIb respectively.0.86
Chung Wong & Ip, 2004 [31]Single centre retrospective studySMA I-III, n = 83Survival pattern, ambulatory statusSurvival probabilities at 20 years: type I 30%; type II 92%; type III 100%)
SMA IIIa and IIIb have a 38 and 68% chance of remaining ambulatory 40 years post disease onset.
0.82
Farrar et al., 2013 [32]Single centre retrospective studySMA I-III, n = 70 (20 SMA I; 31 SMA II; 14 SMA IIIa, 5 SMA IIIb)Survival, ambulatory status40 year survival probability of 0, 52 and 100% for SMA type I, II and III respectively. Ambulatory probability at 20 years of age = 16% for type IIIa and 100% type IIIb0.91
Piepers et al., 2008 [33]Multicentre, prospective study, follow up 30 monthsSMA IIIb and IV, median age disease onset 22.2 years (range 10–37 years), n = 12Muscle strength (MRC grading), respiratory function (FVC), QoL (SF-36)No significant changes in outcome measures after 2.5 years follow up0.70
Kaufmann P, et al., 2012 [34]Multicenter, prospective study, average follow up 25 monthsSMA II and III, mean baseline age 11.3 ± 9.4 years, n = 85 (41 SMA II, 38 SMA III)Motor function (HFMS, HFMSE, GMFM), respiratory function (FVC), QoL (PedsQL), muscle strength (myometry)Decline in motor function (−1.71 HFMSE; −4.39 GMFM; − 1.26 HFM) and respiratory function (− 3%) over time when evaluated beyond 12 months0.95
Pera et al., 2019 [35]Muticentre longitudinal study over 12 monthsSMA II and III, total cohort age range 2.7–49.7 years, n = 114. (n = 27 aged > 15 years)Motor function (RULM)RULM changes over 12 months − 0.6 (2.35SD), SMA II: 0.2 (1.8SD, n = 14); non-ambulant SMA III − 1.7 (2.4SD, n = 6); ambulant SMA III − 1.4 (2.7SD)1.00
Wadman et al., 2018 [22]Single centre cross-sectional studySMA I-IV, age range = 1–77.5 years (60% ≥18 years), n = 180Motor function (HFMS, HFMSE), muscle strength (MRC)Progressive loss of muscle strength and function. Average decline was 1 MRC point and 0.5 HFMSE points per year.0.91
Mercuri et al., 2016 [36]Multicentre retrospective study with 12 month observation periodSMA II and III, baseline age = 2.5–55.5 years, mean age = 10.65 years, n = 268Motor function (HFMSE)Ambulant: 12 month change not associated with age
Non-ambulant: 12 month change different among various age groups with slow functional loss (− 0.93 points/year) after age 15 years
0.95
Sivo et al., 2015 [37]Single centre longitudinal study over 12 monthSMA II and III, age = 3.5–29.0 years (mean = 10.22) n = 74 (SMA II = 70, SMA III = 4)Motor Function (ULM, HFMSE)The mean 12 month changes in the 9 patients > 18 years was 0.11 (range − 1 to + 1) for HFMSE and 0 (range − 1 to + 1) for ULM0.82
Werlauff, Vissing & Steffensen 2012 [38]Single centre, longitudinal prospective study, median follow up = 17 yearsSMA II and III, baseline age = 6–53, n = 30 (23 SMA II, 7 SMA III)Motor function (Brooke upper limb scale, EK), muscle strength (MMT)Upper limb muscle strength declines slowly over time, but can only be detected if monitored over several years.0.90
Montes et al., 2018 [39]Multicentre longitudinal study, follow up 0.5–9 yearsSMA IIIa and IIIb, n = 15 ≥ 20 yearsMotor function (6MWT)Loss of function evident with 6MWT mean annual rate of change − 9.7 m/year0.82
Vuillerot et al., 2013 [40]Multicentre, retrospective study, follow up over 1.2–66 monthsSMA II (n = 44, mean age 11.5 ± 5.0, range 5.7–27); SMA III (n = 59, mean age 18.7 ± 12.3, range 6.2–59),Motor function (MFM-32)SMA II follow up > 6 months: − 0.9 points/year
SMA III follow up > 6 months: − 0.6 points/year
0.77
Russman et al., 1996 [41]Multicentre prospective study, 2 year follow upSMA types II and III, n = 159 (40 patients
> 16 years)
Motor function, ability to sit or walkSlow loss of function, primarily related to maximum function achieved and age of onset. 50% of SMA III with onset aged 2–6 years lost walking ability by age 44 years.0.70
Iannaccone et al., 2000 [42]Longitudinal study, 2–6 year follow upSMA type not specified, n = 30 aged ≥15 years (mean 30.3 ± 11.2 years)Muscle strength (TMS in kg through myometry) and motor functionPatients age > 15 years had a mean change of − 0.4 in TMS0.86
Carter et al., 1995 [43]Single centre, prospective study, 10 year follow upSMA II (mean age 17 ± 14 years) and III (mean age 40 ± 20 years), n = 45Muscle strength (MMT)Mean decline in combined MMT score per decade:
SMA II = -0.24,
SMA III = not significant
0.78
Durmus et al., 2017 [44]Single centre cross-sectional studySMA IIIb, mean age = 23.52 years (13–48), n = 25Muscle MRI, muscle strength (MRC)Significant correlation of loss in muscle strength with time in iliopsoas and triceps but not in other muscles.0.70
Deymeer, 2008 [26]Single centre prospective study, ≥10 year follow upSMA IIIb, median age of onset 12.5 years (range 9–18 years), n = 10Muscle strength (MRC)Decline usually ≤ 1 MRC grade for each 5-year period in each muscle group, with consistent patterns amongst each patient. Triceps, iliopsoas, thigh adductors and quadriceps femoris preferentially affected0.67
  1. Abbreviations: 6MWT Six-minute walk test, EK Egen Klassifikation, FVC Forced vital capacity, GMFM Gross Motor Function Measure, HFMS Hammersmith Functional Motor Scale, HFMSE Expanded Hammersmith Functional Motor Scale, MFM Motor Function Measure, MMT Manual muscle testing, MRC Medical Research Council, QoL Quality of Life, RULM Revised Upper Limb Module, TMS Total Muscle Score, ULM Upper Limb Module
  2. a Traditional SMA classifications: Type I - symptom onset < 6 months, unable to sit independently; Type II - symptom onset between 6 and 18 months, achieved ability to sit independently; Type IIIa - symptom onset < 3 years, achieved ability to walk independently; Type IIIb – symptom onset > 3 years, achieved ability to walk independently; Type IV - adult onset SMA
  3. bThe data presented summarizes salient findings relevant to the natural history of adults with SMA, results pertinent to childhood trajectories have been omitted
  4. c Independently rated by at least two of the study authors using the QUALSYST assessment tool with higher scores indicating lower risk of bias and thus greater methodological rigour (> 0.8 = ‘Strong’, 0.71–.0.79 = ‘Good’, 0.50–0.70 = ‘Adequate’; < 0.50 = ‘Limited’)