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. Further, we investigated the association between clinical functional scores and sleep questionnaire scores. Among SMA patients, better motor and limb function was associated with better subjective sleep quality (p's < 0.05). Clinicians should consider sleep quality in patient care and future studies are needed to better understand these relationships

PROCEEDINGS OF THE XXI CONGRESS OF THE ITALIAN ASSOCIATION OF MYOLOGY: Digital EditionDecember 01-04, 2021 Neurofilament light chain and Profilin-1 in adult SMA patients under nusinersen treatment: 26-months follow-up

As an update of our study in 30 adult SMA type 3 patients we tested as potential biomarkers Neurofilament light chain (NfL) and Profilin-1 (PFN-1) during a 26 months follow-up (timepoint M6). PFN-1 is a small actin-binding protein required in both the presynaptic and the postsynaptic compartment with a role in regulating cytoskeletal architecture and dynamics of neurons (Witke, 2004). CSF NfL was tested with an enzyme-linked immunosorbent assay (ELISA) kit (UmanDiagnostics, Sweden). PFN-1 was measured with a commercial manual ELISA kit (Cusabio, China) in CSF samples of 6 patients (3 sitters 3 walkers) at time points L1, L3 and M2 and in every available serum sample from time point L1 to time point M6; 19 serum samples of healthy donors as a control group. Mean NfL at M6 was 381.83 ± 455.71 ng/l, slightly higher than baseline but not significantly different from M3. PFN-1 concentration in all 18 CSF samples was below the lower limit of quantification (< 31.25 ng/l). Serum PFN-1 at baseline was higher in SMA group than in healthy controls (mean 1016 vs 608 ng/l, p = 0.001 Student’s t test). PFN-1 showed a complex dynamic during loading phase, with a significant reduction at L4 compared to baseline. No correlation was found with NfL and motor scores at each time point. PFN-1 as an exploratory cytoskeletal biomarker changed significantly during the first two months of treatment. To our knowledge this is the first report of PFN-1 determination in serum of SMA patients

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. SMA patients showed poorer performance in visuospatial abilities, executive functions and language as compared to healthy controls. In the SMA sample, patients with greater motor difficulties had lower performance in attention, but higher performance in measures of language, verbal fluency, and memory. In men, but not women, cognitive test performance was associated with motor functioning. Our findings showing cognitive changes in SMA type III may reflect the presence of intrinsic brain pathology and cognitive adaptation mechanisms following physical dysfunction, which may be mediated by other factors, such as sex

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). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy

Muscle MRI and functional outcome measures in Becker muscular dystrophy

Abstract 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. In this study, 51 molecularly confirmed BMD patients (aged 7–69 years) underwent muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the time of the MRI, and subsequently after one year. We confirmed a pattern of fatty substitution involving mainly the hip extensors and most thigh muscles. Severity of muscle fatty substitution was significantly correlated with specific DMD mutations: in particular, patients with an isolated deletion of exon 48, or deletions bordering exon 51, showed milder involvement. Fat infiltration scores correlated with baseline functional measures, and predicted changes after 1 year. We conclude that in BMD, skeletal muscle MRI not only strongly correlates with motor function, but also helps in predicting functional deterioration within a 12-month time frame

Moderate Intensity Training Impact on the Inflammatory Status and Glycemic Profiles in NOD Mice

The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic β-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1β were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window

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

none19noObjective: 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. Concurrent motor function evaluation included the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), the 6 min walking test (6MWT). Results: 189 completed questionnaires were collected during a 14 months' treatment period. 78 patients were included (7 SMA2 and 69 SMA3 and 2 SMA4) with mean disease duration at first nusinersen administration of 33.2 years (± 12.5 years). All the scores for each INQoL domain (weakness, fatigue, activities, independence, social relationship, emotions, body images) and the derived QoL total score, significantly improved during the observation period, except the muscle locking and pain items. Exploratory analyses suggested that emotions and social relationships were more relevant issues for females compared to males. Social relationships were affected also by a longer disease duration (> 30 years). In SMA3 non-walker patients, activities ameliorate better compared to walkers. The HFMSE and RULM significantly improved from baseline; however, no associations with QoL total score and weakness, activities or independence were demonstrated. Conclusion: In our cohort, adult SMA patients showed a global improvement at the INQoL assessment over 14 months of nusinersen treatment. QoL assessment is relevant to SMA multidisciplinary evaluation.noneBonanno, Silvia; Zanin, Riccardo; Bello, Luca; Tramacere, Irene; Bozzoni, Virginia; Caumo, Luca; Ferraro, Manfredi; Bortolani, Sara; Sorarù, Gianni; Silvestrini, Mauro; Vacchiano, Veria; Turri, Mara; Tanel, Raffaella; Liguori, Rocco; Coccia, Michela; Mantegazza, Renato Emilio; Mongini, Tiziana; Pegoraro, Elena; Maggi, LorenzoBonanno, Silvia; Zanin, Riccardo; Bello, Luca; Tramacere, Irene; Bozzoni, Virginia; Caumo, Luca; Ferraro, Manfredi; Bortolani, Sara; Sorarù, Gianni; Silvestrini, Mauro; Vacchiano, Veria; Turri, Mara; Tanel, Raffaella; Liguori, Rocco; Coccia, Michela; Mantegazza, Renato Emilio; Mongini, Tiziana; Pegoraro, Elena; Maggi, Lorenz

Mammography and MRI for screening women who underwent chest radiation therapy (lymphoma survivors): recommendations for surveillance from the Italian College of Breast Radiologists by SIRM

Women who underwent chest radiation therapy (CRT) during pediatric/young-adult age (typically, lymphoma survivors) have an increased breast cancer risk, in particular for high doses. The cumulative incidence from 40 to 45\ua0years of age is 13-20\ua0%, similar to that of BRCA mutation carriers for whom contrast-enhanced magnetic resonance imaging (MRI) is recommended. However, in women who underwent CRT, MRI sensitivity is lower (63-80\ua0%) and that of mammography higher (67-70\ua0%) than those observed in women with hereditary predisposition, due to a higher incidence of ductal carcinoma in situ with microcalcifications and low neoangiogenesis. A sensitivity close to 95\ua0% can be obtained only using mammography as an adjunct to MRI. Considering the available evidence, women who underwent CRT before 30 receiving a cumulative dose 6510\ua0Gy should be invited after 25 (or, at least, 8\ua0years after CRT) to attend the following program: 1. interview about individual risk profile and potential of breast imaging; 2. annual MRI using the same protocol recommended for women with hereditary predisposition; 3. annual bilateral two-view full-field digital mammography or digital breast tomosynthesis (DBT) with synthetic 2D reconstructions. Mammography and MRI can be performed at once or alternately every 6\ua0months. In the case of MRI or contrast material contraindications, ultrasound will be performed instead of MRI. Reporting using BI-RADS is recommended. At the age for entering population screening, the individual risk profile will be discussed with the woman about opting for only mammography/DBT screening or for continuing the intensive protocol