Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study

Chabanon, A.; Seferian, A.; Daron, Aurore; Péreón, Yann; Cances, C.; Vuillerot, Carole; Waele, Liesbeth De; Cuisset, Jean‐Marie; Laugel, Vincent; Schara, Ulrike; Gidaro, T.; Gilabert, Stéphanie; Hogrel, Jean‐Yves; Baudin, Pierre‐Yves; Carlier, Pierre; Fournier, Emmanuel; Lowes, Linda; Hellbach, Nicole; Seabrook, Timothy J.; Toledano, Elie; Annoussamy, M.; Servais, Laurent

doi:10.1371/journal.pone.0201004

Cited by 121 publications

(124 citation statements)

References 60 publications

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“…Nevertheless, a previous study reported an increased T2 in the upper leg in SMA patients, ranging from 34.3 to 41.3 ms, but this cannot be directly compared with our data as the authors used a multi-exponential signal model that does not account for EPG effects. 23 Moreover, Bonati et al found a strongly increased T2…”

Section: Discussionmentioning

confidence: 98%

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Quantitative MRI of skeletal muscle in a cross‐sectional cohort of patients with spinal muscular atrophy types 2 and 3

et al. 2020

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The aim of this study was to document upper leg involvement in spinal muscular atrophy (SMA) with quantitative MRI (qMRI) in a cross‐sectional cohort of patients of varying type, disease severity and age. Thirty‐one patients with SMA types 2 and 3 (aged 29.6 [7.6‐73.9] years) and 20 healthy controls (aged 37.9 [17.7‐71.6] years) were evaluated in a 3 T MRI with a protocol consisting of DIXON, T2 mapping and diffusion tensor imaging (DTI). qMRI measures were compared with clinical scores of motor function (Hammersmith Functional Motor Scale Expanded [HFMSE]) and muscle strength. Patients exhibited an increased fat fraction and fractional anisotropy (FA), and decreased mean diffusivity (MD) and T2 compared with controls (all P < .001). DTI parameters FA and MD manifest stronger effects than can be accounted for the effect of fatty replacement. Fat fraction, FA and MD show moderate correlation with muscle strength and motor function: FA is negatively associated with HFMSE and Medical Research Council sum score (τ = −0.56 and −0.59; both P < .001) whereas for fat fraction values are τ = −0.50 and −0.58, respectively (both P < .001). This study shows that DTI parameters correlate with muscle strength and motor function. DTI findings indirectly indicate cell atrophy and act as a measure independently of fat fraction. Combined these data suggest the potential of muscle DTI in monitoring disease progression and to study SMA pathogenesis in muscle.

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Section: Discussionmentioning

confidence: 98%

“…21,22 Quantitative MRI in SMA has not been studied in detail. 16,23,24 The application of qMRI in diseased muscle proposes some technical challenges, as T2 signal and DTI parameters can be influenced or are confounded by fat present in the muscle. 21,25,26 This study aims to document qMRI properties of muscle tissue in SMA.…”

Section: Introductionmentioning

confidence: 99%

Quantitative MRI of skeletal muscle in a cross‐sectional cohort of patients with spinal muscular atrophy types 2 and 3

et al. 2020

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“…Several relatively small studies previously evaluated the natural history of lung function in patients with SMA [10][11][12][13][14][30][31][32][33][34][35][36][37][38]. FVC was studied most frequently and progressive FVC decline has been reported, caused by progressive respiratory muscle failure, limited lung and chest wall growth, and scoliosis progression [39,40].…”

Section: Discussionmentioning

confidence: 99%

“…It is the most important cause of morbidity and mortality in patients with SMA [2,6]. Previous longitudinal studies of lung function included relatively small numbers of SMA patients, did not encompass the entire spectrum of severity or ages, focused on Forced Vital Capacity only, or had limited follow-up [10][11][12][13][14][15]. Additional natural history data of SMA patients treated according to the standards of care [6], but prior to receiving recently introduced therapies, are important to further improve timing of supportive care and to explore its potential as an outcome measure to evaluate longer-term effects of new treatment strategies [2,9,16,17].…”

Section: Introductionmentioning

confidence: 99%

Natural history of lung function in spinal muscular atrophy

Wijngaarde

Veldhoen

Eijk

et al. 2020

Orphanet J Rare Dis

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Background: Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail. Results: We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV 1), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV 1 and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV 1 ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from − 0.1% to − 1.4% for FEV 1 , − 0.2% to − 1.4% for FVC, and + 0.2% to − 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV 1 values measured in either sitting or supine position. Conclusions: Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV 1 or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.

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“…Hereditary proximal Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder with predominantly infantile or childhood onset and is caused by deficiency of the survival motor neuron (SMN) protein due to loss of function of the SMN1 gene [1]. SMA is characterised by progressive loss of muscle strength and motor function with a large clinical variety ranging from severe hypotonia in the first months of life (type 1), stalled gross motor development but the ability to sit without support (type 2), difficulties with or the loss of ambulation later in life (type 3) to relatively mild impairments in adulthood (type 4) [2][3][4][5]. Fatigability, defined as the inability to sustain repetitive physical activities, is increasingly being recognized as an important additional dimension of physical impairments and a target for therapeutic interventions [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Fatigability in spinal muscular atrophy: validity and reliability of endurance shuttle tests

Bartels

Groot

Habets

et al. 2020

Orphanet J Rare Dis

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Background: To determine construct validity and test-retest reliability of Endurance Shuttle Tests as outcome measures for fatigability of remaining motor functions in children and adults with Spinal Muscular Atrophy (SMA) across the severity spectrum. Results: We assessed the Endurance Shuttle-Nine Hole Peg Test (ESNHPT), − Box and Block Test (ESBBT) and-Walk Test (ESWT) in 61 patients with SMA types 2-4, 25 healthy controls (HC) and 15 disease controls (DC). Convergent validity, discriminative validity and test-retest reliability were investigated. Additionally, we compiled the Endurance Shuttle Combined Score (ESTCS) by selecting the most relevant endurance test of each individual. 54, 70 and 73% of patients with SMA demonstrated increased fatigability on the ESNHPT, ESBBT and the ESWT. Endurance response in SMA was characterized by a decrease in muscle strength, an increase in muscle fatigue and an increase in motor adaptions, thereby confirming convergent validity. Patients with SMA showed increased drop-out rates and a shorter endurance time compared to HC and DC demonstrating good discriminative validity. Test-retest reliability was moderate to excellent (ICC's ranging from .78 to .91) with a trend towards better performance on retest. The ESTCS increased sample size and drop-out rate up to 100 and 85%. Conclusions: Fatigability is an important additional dimension of physical impairments across the severity spectrum in children and adults with SMA. The EST's are reliable and valid to document fatigability of walking, proximal-and distal arm function in SMA and thus are promising outcome measures for use in clinical trials.

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Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study

Cited by 121 publications

References 60 publications

Quantitative MRI of skeletal muscle in a cross‐sectional cohort of patients with spinal muscular atrophy types 2 and 3

Quantitative MRI of skeletal muscle in a cross‐sectional cohort of patients with spinal muscular atrophy types 2 and 3

Natural history of lung function in spinal muscular atrophy

Fatigability in spinal muscular atrophy: validity and reliability of endurance shuttle tests

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