Sensory Nerve Action Potential Analysis in a Cohort of Patients With Spinal Muscular Atrophy Aged 12 Years and Older.

Introduction/aims: Survival Motor Neuron 1 (SMN1)-related spinal muscular atrophy (SMA) is characterized by α-motor neuron degeneration, with sensory function assumed to be clinically preserved. However, recent studies in severely affected patients and animal models have challenged this view. Therefore, we assessed the maximum sensory nerve action potential (SNAP) amplitude of the median nerve in patients with SMA and examined its changes during treatment with SMN-splicing modifying therapies.

Patient-specific responses to splice-modifying treatments in spinal muscular atrophy fibroblasts.

The availability of three therapies for the neuromuscular disease spinal muscular atrophy (SMA) highlights the need to match patients to the optimal treatment. Two of these treatments (nusinersen and risdiplam) target splicing of , but treatment outcomes vary from patient to patient. An incomplete understanding of the complex interactions among SMA genetics, SMN protein and mRNA levels, and gene-targeting treatments, limits our ability to explain this variability and identify optimal treatment strategies for individual patients.

Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3.

Background And Objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA.

Exploring functional strength changes during nusinersen treatment in symptomatic children with SMA types 2 and 3.

The Hammersmith Functional Motor Scale-Expanded (HFMSE) is a validated outcome measure for monitoring changes in functional strength in patients with spinal muscular atrophy (SMA). The objective of this study was to explore changes in HFMSE item-scores in children with SMA types 2 and 3a treated with nusinersen over a period of six to twenty months. We stratified patients according to motor ability (sitting and walking), and calculated numbers and percentages for each specific improvement (positive score change) or decrease (negative score change) for the total group and each subgroup and calculated frequency distributions of specific score changes.

Shaping research for people living with co-existing mental and physical health conditions: A research priority setting initiative from the United Kingdom.

Introduction: Those with severe and enduring mental ill health are at greater risk of long-term physical health conditions and have a reduced life expectancy as a result. Multiple factors compound this health inequality, and the need for setting research priorities in this area is highlighted with physical and mental healthcare services being separate, and limited multimorbidity research.

Methods: The aim of this exercise was to work in partnership with healthcare professionals and carers, family, friends and individuals with lived experience of both mental and physical health conditions, to set research priorities to help people with mental health conditions to look after their physical health.

Natural History of Mandibular Function in Spinal Muscular Atrophy Types 2 and 3.

Background: Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course.

Objective: In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3.

Do young people who self-harm experience cognitions and emotions related to post-traumatic growth?

Background: Adolescent self-harm is a vast public health concern with self-harm rates increasing each year. Looked-after adolescents are a group at increased risk of self-harm owing to adverse life-events and attachment issues, giving rise to difficulties with problem solving and relationship difficulties (Ogundele, 2020). Whilst research into risk factors of self-harm is plentiful, fewer studies have explored what factors might facilitate self-harm recovery.

How do schools influence the emotional and behavioural health of their pupils? A multi-level analysis of 135 schools in the Born in Bradford inner city multi-ethnic birth cohort.

Purpose: To estimate variation in emotional and behavioural problems between primary schools in Bradford, an ethnically diverse and relatively deprived city in the UK.

Methods: We did a cross-sectional analysis of data collected from 2017 to 2021 as part of the 'Born In Bradford' birth cohort study. We used multilevel linear regression in which the dependent variable was the Strengths and Difficulties Questionnaire (SDQ) total score, with a random intercept for schools.

Monitoring Nusinersen Treatment Effects in Children with Spinal Muscular Atrophy with Quantitative Muscle MRI.

Background: Spinal muscular atrophy (SMA) is caused by deficiency of survival motor neuron (SMN) protein. Intrathecal nusinersen treatment increases SMN protein in motor neurons and has been shown to improve motor function in symptomatic children with SMA.

Objective: We used quantitative MRI to gain insight in microstructure and fat content of muscle during treatment and to explore its use as biomarker for treatment effect.

A Novel Variant in Causing Muscle Weakness and Concomitant Hypercontractile Phenotype.

A novel variant of unknown significance c.8A > G (p.Glu3Gly) in was detected in two unrelated families.

Digital health literacy and digital engagement for people with severe mental ill health across the course of the COVID-19 pandemic in England.

Background: An unprecedented acceleration in digital mental health services happened during the COVID-19 pandemic. However, people with severe mental ill health (SMI) might be at risk of digital exclusion, partly because of a lack of digital skills, such as digital health literacy. The study seeks to examine how the use of the Internet has changed during the pandemic for people with SMI, and explore digital exclusion, symptomatic/health related barriers to internet engagement, and digital health literacy.

Enhanced low-threshold motor unit capacity during endurance tasks in patients with spinal muscular atrophy using pyridostigmine.

Objective: To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA).

Methods: We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements.

Feasibility and tolerability of multimodal peripheral electrophysiological techniques in a cohort of patients with spinal muscular atrophy.

Objective: Electrophysiological techniques are emerging as an aid in identifying prognostic or therapeutic biomarkers in patients with spinal muscular atrophy (SMA), but electrophysiological assessments may be burdensome for patients. We, therefore, assessed feasibility and tolerability of multimodal peripheral non-invasive electrophysiological techniques in a cohort of patients with SMA.

Methods: We conducted a single center, longitudinal cohort study investigating the feasibility and tolerability of applying multimodal electrophysiological techniques to the median nerve unilaterally.

Longitudinal prospective cohort study to assess peripheral motor function with extensive electrophysiological techniques in patients with Spinal Muscular Atrophy (SMA): the SMA Motor Map protocol.

Background: Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e.

Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study.

Background: Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure.

Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2-4.

Hereditary proximal spinal muscular atrophy causes weakness and increased fatigability of repetitive motor functions. The neuromuscular junction is anatomically and functionally abnormal in patients with spinal muscular atrophy. Pharmacological improvement of neuromuscular transmission may therefore represent a promising additional treatment strategy.

Inflammatory markers in cerebrospinal fluid of paediatric spinal muscular atrophy patients receiving nusinersen treatment.

Spinal muscular atrophy (SMA) is a progressive motor neuron disease with onset during infancy or early childhood. Recent therapeutic advances targeting the genetic defect that underlies SMA improved survival in patients with infantile onset SMA (type 1) and improved motor function in SMA type 1-3. The most commonly used therapy for SMA, the antisense oligonucleotide nusinersen, is delivered by repeated intrathecal injections.

Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study.

Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in children up to 12 years. Population-based assessments of treatment efficacy are limited and confined to select cohorts of patients. We performed a nationwide, population-based, single-centre cohort study in children with spinal muscular atrophy younger than 9.

Sleep health among people with severe mental ill health during the COVID-19 pandemic: Results from a linked UK population cohort study.

Objectives: Sleep problems are a transdiagnostic feature of nearly all psychiatric conditions, and a strong risk factor for initial and recurrent episodes. However, people with severe mental ill health (SMI) are often excluded from general population surveys, and as such the extent and associates of poor sleep in this population are less well understood. This study explores sleep health in an SMI sample during the COVID-19 pandemic, using multiple regression to identify risk factors, including daily routine, wellbeing and demographics.

Influences on the physical and mental health of people with serious mental ill-health during the COVID-19 pandemic: a qualitative interview study.

Purpose: People with severe mental ill-health (SMI) experience profound health inequalities. The Optimizing Wellbeing in Self-isolation study (OWLS) explored the effects of the COVID-19 pandemic restrictions on people with SMI, including how and why their physical and mental health may have changed during the pandemic.

Methods: The OLWS study comprised two surveys and two nested qualitative studies.

Measuring the digital divide among people with severe mental ill health using the essential digital skills framework.

Aims: Amid the vast digitalisation of health and other services during the pandemic, people with no digital skills are at risk of digital exclusion. This risk might not abate by the end of the pandemic. This article seeks to understand whether people with severe mental ill health (SMI) have the necessary digital skills to adapt to these changes and avoid digital exclusion.

Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study.

Background: Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.

A Year Into the Pandemic: The Diversity of Experience Amongst People With Severe Mental Ill Health.

Background: The COVID-19 pandemic has amplified pre-existing health inequalities and people with severe mental ill health (SMI) are one of the groups at greatest risk. In this study, we explored the effects of the pandemic and pandemic restrictions on people with SMI during the first year of the pandemic.

Methods: We conducted a longitudinal study in a sample of people with SMI.