Investigating a Domain Adaptation Approach for Integrating Different Measurement Instruments in a Longitudinal Clinical Registry.

In a longitudinal clinical registry, different measurement instruments might have been used for assessing individuals at different time points. To combine them, we investigate deep learning techniques for obtaining a joint latent representation, to which the items of different measurement instruments are mapped. This corresponds to domain adaptation, an established concept in computer science for image data.

Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort.

Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease affecting the peripheral and central nervous system and is caused by bi-allelic variants in the GAN gene, leading to loss of functional gigaxonin protein. A treatment does not exist, but a first clinical trial using a gene therapy approach has recently been completed. Here, we conducted the first systematic study of GAN patients treated by German-speaking child neurologists.

Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study.

Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH).

Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region.

Postnatal management of preterm infants with spinal muscular atrophy: experience from German newborn screening.

Background: The introduction of newborn screening (NBS) for spinal muscular atrophy (SMA) has increased the early diagnosis of 5q-associated SMA in presymptomatic and symptomatic preterm infants. National and international recommendations for treating preterms and newborns < 38 weeks of gestational age are unavailable. Our retrospective multicentre study aimed to evaluate the postnatal clinical course of preterm infants with 5q-associated SMA diagnosed since the implementation of NBS in Germany in 2021 and to summarize the German experience regarding the decision-making process for available treatment regimens for preterm infants with ≤ 3 survival of motor neuron 2 (SMN2) copies.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2.

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland.

Evaluating case management for caregivers of children with spinal muscular atrophy type I and II-an exploratory, controlled, mixed-methods trial.

Introduction: Spinal muscular atrophy (SMA) is a rare neuromuscular disease requiring various clinical specialists and therapists to provide care. Due to the disease's dynamic nature and the long distances between specialized centers and local providers, integrating care between disciplines can be challenging. Care that is inadequately integrated can compromise the quality of care and become a burden for patients and families.

Whole-Genome Sequencing Identified New Structural Variations in the Gene That Cause Duchenne Muscular Dystrophy in Two Girls.

Dystrophinopathies are the most common muscle diseases, especially in men. In women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare due to X-chromosomal inheritance. We present two young girls with severe muscle weakness, muscular dystrophies, and creatine kinase (CK) levels exceeding 10,000 U/L.

Mechanographic analysis of the timed 4 stair climb test - methodology and reference data of healthy children and adolescents.

Objectives: The timed 4 stair climb test (4SC) is an accepted and widely used tool to assess motor function of patients with neuromuscular diseases. We aimed to establish reference data for the 4SC, and for mechanographic analysis of ascent (4SC-Up) and descent (4SC-Dn) in healthy children and adolescents.

Methods: We used a custom-made staircase measuring device to assess force, power and velocity during the ascent of 4 stairs in healthy subjects.

Improvements in Walking Distance during Nusinersen Treatment - A Prospective 3-year SMArtCARE Registry Study.

Background And Objectives: Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients.

Caregiver Burden of Spinal Muscular Atrophy: A Systematic Review.

Objective: The objective of our study was to review, synthesize, and grade published evidence of caregiver burden of spinal muscular atrophy (SMA), a rare autosomal-recessive neuromuscular disease.

Methods: We searched Embase and PubMed for full-text articles published from inception up until 28 February, 2022, reporting results from studies of caregiver burden (i.e.

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study.

Background: The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA.

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Participation of patients and relatives in research means that those affected are involved in the research process in a partnership role. Despite the growing importance of participatory approaches and the large number of available concepts, many researchers and patients are faced with the question of how participatory research can be realized and organized in concrete terms. Here we report on our experiences with two different forms of patient participation in research in the context of pediatric health care research at a university hospital: (1) In a project for the development and evaluation of a case management for patients with spinal muscular atrophy, patient representatives have an consultative role.

Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy.

5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment.

Risdiplam in types 2 and 3 spinal muscular atrophy: A randomised, placebo-controlled, dose-finding trial followed by 24 months of treatment.

Background And Purpose: Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an orally administered molecule that modifies SMN2 pre-mRNA splicing to increase functional SMN protein.

Methods: SUNFISH Part 1 was a dose-finding study conducted in 51 individuals with types 2 and 3 SMA aged 2-25 years.

Deep dynamic modeling with just two time points: Can we still allow for individual trajectories?

Longitudinal biomedical data are often characterized by a sparse time grid and individual-specific development patterns. Specifically, in epidemiological cohort studies and clinical registries we are facing the question of what can be learned from the data in an early phase of the study, when only a baseline characterization and one follow-up measurement are available. Inspired by recent advances that allow to combine deep learning with dynamic modeling, we investigate whether such approaches can be useful for uncovering complex structure, in particular for an extreme small data setting with only two observations time points for each individual.

Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy.

Background And Purpose: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the past 4 years, but treatment responses differ remarkably between individuals, and therapeutic decision-making remains challenging, underlining the persistent need for validated biomarkers.

Methods: We applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and enzyme-linked immunosorbent assay.

Parents' Perspectives on Diagnosis and Decision-Making regarding Ventilator Support in Children with SMA Type 1.

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder with a broad clinical spectrum. The most severe phenotype-SMA type 1-is characterized by marked muscle weakness also affecting bulbar and respiratory function. Life expectancy of children with SMA type 1 is expected to be less than 2 years without ventilator support or disease-specific drug treatment.

Costs of Illness of Spinal Muscular Atrophy: A Systematic Review.

Objectives: The objective of our study was to conduct a systematic literature review of estimates of costs of illness of spinal muscular atrophy (SMA).

Methods: We searched MEDLINE (through PubMed), CINAHL, Embase, Web of Science, National Health Service Economic Evaluation Database, and the National Health Service Health Technology Assessment Database for studies published from inception up until 31 August, 2020, reporting direct medical, direct non-medical, and/or indirect costs of any phenotype of SMA. Two reviewers independently screened records for eligibility, extracted the data, and assessed studies for risk of bias using the Newcastle-Ottawa Scale.