Congenital muscular dystrophies (CMDs) are a heterogeneous group of genetic neuromuscular disorders. They usually occur at birth or in early childhood, with delayed acquisition of motor milestones, ...and diffuse muscle weakness. A dystrophic pattern is evident on the muscle biopsy. They are highly variable both in terms of severity and clinical evolution and in terms of pathogenetic biochemical mechanisms. The aim of this review is to collect and summarize the current knowledge of motor function in pediatric patients with congenital muscular dystrophies and the instruments used to assess it. This scoping review was conducted using the methodology of PRISMA (extension for Scoping Reviews, PRISMA-ScR). Two databases were queried from January 2002 to November 2022. Articles were identified based on title and abstract. Full-text papers published in peer-reviewed English-language journals were selected. It emerged that motor functional aspects are still underinvestigated in CMD patients, probably due to the rarity of these conditions and the phenotypic variability. The scales used to assess motor function are heterogeneous, as are the age groups considered. Finally, the predominant type of research design is cross-sectional; few studies analyze the progression of motor function over time. All these factors make it difficult to correlate the results of different publications and stress the need for more accurate and shared protocols for assessing motor function in these patients.
In clinical practice and research, innovative digital technologies have been proposed for the characterization of neuromuscular and movement disorders through objective measures. Among these, ...wearable devices prove to be a suitable solution for tele-monitoring, tele-rehabilitation, and daily activities monitoring. Inertial Measurement Units (IMUs) are low-cost, compact, and easy-to-use wearable devices that evaluate kinematics during different movements. Kinematic variables could support the clinical evaluation of the progression of some neuromuscular diseases and could be used as outcome measures. The current review describes the use of IMUs for the biomechanical assessment of meaningful outcome measures in individuals affected by Duchenne muscular dystrophy (DMD). The PRISMA methodology was used and the search was conducted in different databases (Scopus, Web of Science, PubMed). A total of 23 articles were examined and classified according to year of publication, ambulatory/non-ambulatory subjects, and IMU positioning on human body. The analysis points out the recent regulatory identification of Stride Velocity 95th Centile as a new endpoint in therapeutic DMD trials when measured continuously from a wearable device, while only a few studies proposed the use of IMUs in non-ambulatory patients. Clinical recognition of reliable and accurate outcome measures for the upper body is still a challenge.
Background and purpose
Advances in multidisciplinary care are extending overall survival in Duchenne muscular dystrophy (DMD) patients. Our research objective was to delineate the clinical ...characteristics of this particular cohort and identify novel challenges associated with the disease.
Methods
Nineteen individuals aged 25–48 years (median 34 years) with a confirmed diagnosis of out‐of‐frame DMD gene mutation were selected.
Results
All patients were mechanically ventilated (5/19 via tracheostomy), with different patterns of cardiomyopathy. Swallowing and nutritional issues were frequent (median body mass index 18.95), with six cases requiring artificial enteral feeding (median age at start 29 years), as well as bone density alterations (11/19, 58%). Only 2/19 had been on long‐term prednisone therapy. Issues requiring at‐home/hospital assistance were respiratory infections (15/19, 79%), gastroenterological symptoms (9/19, 47%, including toxic megacolon and rectal perforation after repeated enemas), metabolic acidosis (2/19, 11%) and recurrent ischaemic strokes (1/19, 5%). From a social perspective, augmented‐alternative communication devices were necessary for 7/19 (37%), with most of the patients being assisted at home and 2/19 institutionalized. Eight/19 (42%) patients experienced psychiatric symptoms (median age at presentation 16 years) and 9/19 (47%) chronic pain (median age at onset 23 years), in both cases treated with psychoactive/analgesic drugs without major adverse events. The patients' subjective perception of physical health resulted in unfavourable scores, whilst the subjective assessment of mental health unexpectedly showed more positive values compared to other chronic neurological conditions.
Conclusions
The analysis of adults living with DMD reveals several new health‐related issues, such as the management of emergencies and safety of pharmacological treatments for psychiatric symptoms, chronic pain management, as well as an increasing caregivers burden.
Background
We report the 4‐year follow‐up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number.
...Methods
The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE‐II).
Results
Forty‐eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE‐II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE‐2 increased significantly in patients younger than 2 years at treatment. In a mixed‐model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not.
Conclusions
Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.
Neumann eigenvalues being non-decreasing with respect to domain inclusion, it makes sense to study the two shape optimization problems \(\min\{\mu_k(\Omega):\Omega \mbox{ convex},\Omega \subset D, ...\}\) (for a given box \(D\)) and \(\max\{\mu_k(\Omega):\Omega \mbox{ convex},\omega \subset \Omega, \}\) (for a given obstacle \(\omega\)). In this paper, we study existence of a solution for these two problems in two dimensions and we give some qualitative properties. We also introduce the notion of {\it self-domains} that are domains solutions of these extremal problems for themselves and give examples of the disk and the square. A few numerical simulations are also presented.
