PND74 MAPPING A QUALITATIVE EXPLORATION OF MEANINGFUL CHANGE IN LATER-ONSET (TYPE II OR III) SPINAL MUSCULAR ATROPHY TO THE HAMMERSMITH FUNCTIONAL MOTOR SCALE EXPANDED (HFMSE)

Summary Objectives The main objective of this study was to assess the three-dimensional facial characteristics of children affected by spinal muscular atrophy (SMA), a severe muscular disorder characterized by hypotonia, areflexia, weakness, and respiratory impairment. Materials/Methods Stereophotogrammetric facial scans from 22 SMA type II patients aged 2–7 years were obtained. Data were analysed using both inter-landmark distances and principal component analysis and compared with data collected from matched control subjects. Results Patients had wider transverse facial diameters, but smaller biocular width. Middle and lower anterior face heights were increased, whereas the mandibular ramus was shorter, with a reduced posterior-to-anterior face height ratio. Facial width-to-length ratio was reduced. In the sagittal plane, mandibular body length, and facial divergence were increased, whereas the gonial angles were decreased. In the horizontal plane, lower facial convexity was greater in patients, whereas mandibular convexity was smaller. Patients had smaller and down-slanted eye fissures, with a larger and more vertically developed nose. Limitations This study assessed a relatively small number of patients, due to the rare frequency of SMA type II. Conclusions/Implications SMA type II children possess peculiar facial alterations that may be due to the altered muscular activity. As feeding problems may derive also by malocclusion and masticatory muscular alterations, a detailed assessment of the craniofacial individual alterations should be considered in the standards of care of these patients.

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Nusinersen in later-onset spinal muscular atrophy

Neurology ◽

10.1212/wnl.0000000000007527 ◽

2019 ◽

Vol 92 (21) ◽

pp. e2492-e2506 ◽

Cited By ~ 55

Author(s):

Basil T. Darras ◽

Claudia A. Chiriboga ◽

Susan T. Iannaccone ◽

Kathryn J. Swoboda ◽

Jacqueline Montes ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Function ◽

Muscular Atrophy ◽

Compound Muscle Action Potential ◽

Extension Study ◽

Type Ii ◽

Open Label ◽

Type Iii ◽

Link Type ◽

Phase 1B

ObjectiveTo report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA).MethodsAnalyses included children from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2–15 years. The extension study was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant (196–413 days). Assessments included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), 6-Minute Walk Test (6MWT), compound muscle action potential (CMAP), and quantitative multipoint incremental motor unit number estimation. Safety also was assessed.ResultsTwenty-eight children were included (SMA type II, n = 11; SMA type III, n = 17). Mean HFMSE scores, ULM scores, and 6MWT distances improved by the day 1,150 visit (HFMSE: SMA type II, +10.8 points; SMA type III, +1.8 points; ULM: SMA type II, +4.0 points; 6MWT: SMA type III, +92.0 meters). Mean CMAP values remained relatively stable. No children discontinued treatment due to adverse events.ConclusionsNusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. These results document the long-term benefit of nusinersen in later-onset SMA, including SMA type III.Clinicaltrials.gov identifierNCT01703988 (ISIS-396443-CS2); NCT02052791 (ISIS-396443-CS12).Classification of evidenceThis study provides Class IV evidence that nusinersen improves motor function in children with later-onset SMA.

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