Long-term progression in type II spinal muscular atrophy

Lucibello, Simona; Pera, Maria Carmela; Carnicella, Sara; Coratti, Giorgia; Sanctis, Roberto De; Messina, Sonia; Mazzone, Elena; Forcina, Nicola; Fanelli, Lavinia; Norcia, Giulia; Antonaci, Laura; Frongia, A.; Pane, Marika

doi:10.1212/wnl.0000000000008166

Cited by 41 publications

(29 citation statements)

References 20 publications

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“…Our results confirm the already described pattern of disease progression in SMA II patients at different ages (3,8). In this paper, we used a new approach, so far not used in SMA, assessing how frequently abilities are lost or gained, irrespective of whether the function was achieved completely or with some compensations.…”

Section: Discussionsupporting

confidence: 89%

Gain and loss of abilities in type II SMA: A 12-month natural history study

Coratti

Lucibello

Pera

et al. 2020

Neuromuscular Disorders

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The advent of clinical trials in spinal muscular atrophy (SMA) has highlighted the need to define patterns of progression using functional scales. It has recently been suggested that the analysis of abilities gained or lost applied to functional scales better reflects meaningful changes. We defined as "gain" a positive change between scores from 0 to either 1 or 2 and as "loss" a negative change from either 2 or 1 to 0.The aim of this study was to describe, over 12 months, which abilities on the Hammersmith Functional Motor Scale Expanded (HFMSE) were more frequently lost or gained in patients with SMA II.The cohort included 614 12-month assessments from 243 patients (age range: 30 months -62.51 years; mean 9.94, SD +7.91).The peak of abilities gained occurred before the age of 5 years while the highest number of lost abilities was found in the group 5-13 years. A correlation between the HFMSE baseline score and the ordinal number of the items was found for both lost (p<0.001) or gained (p<0.001) activities. No correlation was found with SMN2 copy number. These findings will have implications for clinical trial design and for the interpretation of real-world data using new therapeutic approaches.

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Section: Discussionsupporting

confidence: 89%

Gain and loss of abilities in type II SMA: A 12-month natural history study

Coratti

Lucibello

Pera

et al. 2020

Neuromuscular Disorders

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“…Our work adds long-term respiratory data from a large international cohort (n = 437) of patients with SMA type 2 and nonambulant type 3 followed up over 8 years. Similar to motor function, 26 , 27 the decline of FVC%P in SMA type 2 and type 3 followed different trajectories across age ranges. In both subtypes, FVC%P declined more steeply from 5 to 13 years (≈4%/y in SMA type 2 and ≈3%/y in type 3), followed by a slower annual progression after 13 years of age (1% in SMA type 2 and 0.9% in type 3).…”

Section: Discussionmentioning

confidence: 86%

“…Recently, the description of the natural history of motor function in SMA types 2 and 3 has identified that, in the early years after diagnosis, an improvement in SMA type 2 can occur, followed by a subsequent decline. 26 This information is essential when planning clinical trials and assessing the efficacy of intervention in a broad population. However, very few studies have focused on respiratory function, and none examined the correlation between respiratory and motor function in a real-world broad population of intermediate SMA.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study

Trucco¹,

Ridout

Scoto

et al. 2021

Neurology

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Objective.To describe the respiratory trajectories and their correlation with motor function in an international paediatric cohort of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA).Methods.Eight-year retrospective observational study of patients in the iSMAc natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC% predicted (FVC%P.), Non-Invasive ventilation (NIV) requirement. Hammersmith functional motor scale (HFMS) and Revised performance of upper limb (RULM) were correlated with respiratory function. We excluded patients in interventional clinical trials and on Nusinersen commercial therapy.Results.There were 437 patients with SMA: 348 type 2, 89 non-ambulant type 3. Mean age at first visit was 6.9(±4.4) and 11.1(±4) years. In SMA type 2 FVC%P declined by 4.2%/year from 5 to 13 years, followed by a slower decline (1.0%/year). In type 3 FVC%P declined by 6.3%/year between 8 and 13 years, followed by a slower decline (0.9%/year). 39% SMA type 2 and 9% type 3 required NIV at median age 5.0(1.8-16.6) and 15.1(13.8-16.3) years. 84% SMA type 2 and 80% type 3 had scoliosis, 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM in both subtypes.Conclusions.In SMA type 2 and non-ambulant type 3 lung function declines differently, with a common levelling after age 13 years. Lung and motor function correlated in both subtypes. Our data further defines the milder SMA phenotypes and provides novel information to benchmark the long-term efficacy of new treatments for SMA.

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“…Disease-modifying treatments have been shown to alter the disease progression for patients with SMA [22][23][24][25], including extending overall and permanent-ventilation free survival, and allowing improvement or maintenance of motor function [26]. The expected trajectory for each SMA type in the era of effective treatments will need to be redefined.…”

Section: Introductionmentioning

confidence: 99%

The Cure SMA Membership Surveys: Highlights of Key Demographic and Clinical Characteristics of Individuals with Spinal Muscular Atrophy

Belter

Jarecki

Reyna

et al. 2020

Journal of Neuromuscular Diseases

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Background: Cure SMA maintains the largest patient-reported database for people affected with spinal muscular atrophy (SMA). In 2017, Cure SMA initiated annual surveys with their membership to collect demographic and disease characteristics, healthcare, and burden of disease information from patients and caregivers. Objective: To summarize results from two large-scale Cure SMA surveys in 2017 and 2018. Methods: Cure SMA database members were invited to complete surveys; these were completed by caregivers for living or deceased individuals with SMA and/or affected adults. Results: In 2017, 726 surveys were completed for 695 individuals with SMA; in 2018, 796 surveys were completed for 760 individuals with SMA. Data from both survey years are available for 313 affected individuals. Age at symptom onset, distribution of SMN2 gene copy number, and representation of each SMA type in the surveys were consistent with that expected in the SMA population. In the 2018 survey, the average age at diagnosis was 5.2 months for SMA type I and the reported mean age at death for this subgroup was 27.8 months. Between survey years, there was consistency in responses for factors that should not change within individuals over time (e.g., reported age at diagnosis). Conclusions: Results from the Cure SMA surveys advance the understanding of SMA and facilitate advocacy efforts and healthcare services planning. Longitudinal surveys are important for evaluating the impact of effective treatments on changing phenotypes, and burden of disease and care in individuals with SMA.

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Long-term progression in type II spinal muscular atrophy

Cited by 41 publications

References 20 publications

Gain and loss of abilities in type II SMA: A 12-month natural history study

Gain and loss of abilities in type II SMA: A 12-month natural history study

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study

The Cure SMA Membership Surveys: Highlights of Key Demographic and Clinical Characteristics of Individuals with Spinal Muscular Atrophy

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