Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;268(5):1792-1802.
doi: 10.1007/s00415-020-10332-5. Epub 2021 Jan 2.

Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study

Affiliations

Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study

Giorgia Querin et al. J Neurol. 2021 May.

Abstract

Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials.

Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later. Longitudinal comparisons were conducted using the Wilcoxon-test for matched data. Responsiveness was estimated using standardized response means (SRM) and a composite score was generated based on the three most significant variables.

Results: Significant functional decline was observed based on SMAFRS (p = 0.019), pinch and knee flexion strength (p = 0.030 and 0.027), MUNIX and MUSIX value in the ADM (p = 0.0006 and 0.043) and in TA muscle (p = 0.025). No significant differences were observed based on cervical MRI measures. A significant reduction was detected in the composite score (p = 0.0005, SRM = -1.52), which was the most responsive variable and required a smaller number of patients than single variables in the estimation of sample size for clinical trials.

Conclusions: Quantitative strength testing, SMAFRS and MUNIX readily capture disease progression in adult SMA patients. Composite multimodal scores increase predictive value and may reduce sample size requirements in clinical trials.

Keywords: Adult SMA; Clinical trial; Longitudinal progression; MUNIX; Outcome measures.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Lefebvre S, Bürglen L, Reboullet S et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155–165 - PubMed
    1. Munsat TL, Davies KE (1992) International SMA consortium meeting (26-28 June 1992, Bonn, Germany). Neuromuscul Disord NMD 1992(2):423–428
    1. Wadman RI, Wijngaarde CA, Stam M et al (2018) Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c–4. Eur J Neurol 25:512–518 - PubMed
    1. Wang CH, Finkel RS, Bertini ES et al (2007) Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 22:1027–1049 - PubMed
    1. Mercuri E, Lucibello S, Pera MC et al (2019) Long-term progression in type II spinal muscular atrophy: a retrospective observational study. Neurology 93:e1241–e1247 - PubMed - PMC

LinkOut - more resources