Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

Introduction/aims: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Neurofilament light chain and profilin-1 dynamics in 30 spinal muscular atrophy type 3 patients treated with nusinersen.

Background And Purpose: The aim was to investigate whether neurofilament light chain (NfL) and profilin-1 (PFN-1) might qualify as surrogate disease and treatment-response biomarkers by correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months.

Methods: Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme-linked immunosorbent assay (ELISA); PFN-1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels.

Subjective Sleep Quality as it Relates to Cognitive and Physical Function in Spinal Muscular Atrophy Patients.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA (n = 21) patients and age-matched controls (n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery.

Adults with spinal muscular atrophy: a large-scale natural history study shows gender effect on disease.

Background: Natural history of spinal muscular atrophy (SMA) in adult age has not been fully elucidated yet, including factors predicting disease progression and response to treatments. Aim of this retrospective, cross-sectional study, is to investigate motor function across different ages, disease patterns and gender in adult SMA untreated patients.

Methods: Inclusion criteria were as follows: (1) clinical and molecular diagnosis of SMA2, SMA3 or SMA4 and (2) clinical assessments performed in adult age (>18 years).

Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study.

Cognitive abilities are often affected in progressive neurodegenerative disorders, but there is a lack of understanding about whether spinal muscular atrophy (SMA) patients experience cognitive deficits and, if so, whether they are associated with clinical factors. A sample of 22 type III SMA patients and 22 healthy controls completed a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning. Clinical severity was assessed using the Hammersmith Functional Motor Scale, the Revised Upper Limb Module and the Six Minute Walk Test.

Quality of life assessment in adult spinal muscular atrophy patients treated with nusinersen.

Objective: To retrospectively evaluate quality of life (QoL) in a large multicenter cohort of adult patients affected by spinal muscular atrophy (SMA) during nusinersen treatment.

Methods: We included adult (≥ 18 years) patients clinically and genetically defined as SMA2, SMA3 and SMA4, who started nusinersen treatment in adulthood. QoL was rated by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire.

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).

Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).

Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72).

Muscle MRI and functional outcome measures in Becker muscular dystrophy.

Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification.

Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies.

We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21).