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The latest medical research on Neuromuscular Medicine

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Systemic Postnatal Corticosteroids, Bronchopulmonary Dysplasia, and Survival Free of Cerebral Palsy.

Cerebral Palsy

Systemic postnatal corticosteroids have been shown to reduce rates of bronchopulmonary dysplasia (BPD) in infants born preterm, but both corticosteroids and BPD are associated with cerebral palsy.

To describe how the association between systemic postnatal corticosteroids and survival free of cerebral palsy varies with the risk of BPD in infants born preterm, and if the association differs between dexamethasone and hydrocortisone, or with age at starting treatment.

This comparative effectiveness research used weighted meta-regression analysis of eligible randomized clinical trials (RCTs) of systemic postnatal corticosteroids reported from June 1989 through March 2022 that included rates of all of BPD, mortality, and cerebral palsy in neonatal intensive care units in 10 countries. Infants born preterm at risk of BPD were included. Data were analyzed from April and July 2024.

Systemic dexamethasone or hydrocortisone.

Type and timing of corticosteroid, control group rate of BPD, and risk difference in survival free of cerebral palsy between corticosteroid and control arms.

Twenty-six RCTs with data on 3700 randomized infants were eligible; 18 (69%) investigated dexamethasone and 8 (31%) hydrocortisone; 12 (46%) started treatment in the first week after birth. There was evidence for a differential association of the type of corticosteroid with the effect of systemic dexamethasone on survival free of cerebral palsy and the risk of BPD in control groups (interaction coefficient, 0.54; 95% CI, 0.25-0.82; P = .001). For dexamethasone, for every 10-percentage point increase in the risk of BPD, the risk difference for survival free of cerebral palsy increased by 3.74% (95% CI, 1.54 to 5.93; P = .002). Dexamethasone was associated with improved survival free of cerebral palsy at a risk of BPD greater than 70%. Conversely, dexamethasone was associated with harm at a risk of BPD less than 30%. There was some evidence for a negative association with hydrocortisone, with possible benefit with risk of BPD less than 30%. There was no strong evidence for a differential effect of timing among those treated with dexamethasone (interaction coefficient, 0.13; 95% CI, -0.04 to 0.30; P = .14).

The findings suggest that dexamethasone (compared with control) was associated with improved rates of survival free of cerebral palsy in infants at high risk of BPD but should be avoided in those at low risk. A role for hydrocortisone is uncertain.

Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals.

Neurology, Neurosurgery and Psychiatry

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype is becoming milder with better risk factor treatments and other care improvements is unknown. In a large longitudinal CADASIL cohort, we determined whether the prognosis has changed over 23 years.

Patients were identified from the Cambridge CADASIL register and the UK Familial stroke study. Change in age at stroke over the time of recruitment was determined using linear mixed-effects model, and the impact of genetic and vascular risk factors on stroke and dementia risk was further evaluated using Cox proportional hazard regression.

A total of 555 patients with CADASIL were recruited between 2001 and 2023. The age of stroke onset significantly increased over time (p<0.001), with the mean age of stroke onset for patients recruited before 2016 (n=265) at 46.7±9.2 years and 51.6±9.5 years for those recruited since 2016 (n=290). Patients recruited since 2016 had lower risks of both stroke (HR 0.36, 95% CI 0.26 to 0.50, p<0.001) and dementia (HR 0.43, 95% CI 0.19 to 0.99, p=0.046) after adjusting for sex, hypertension history, smoking status, epidermal growth factor-like repeat position and calendar effect.

The clinical phenotype of CADASIL is improving. While this may be partly explained by reduced vascular risk factors such as smoking and the identification of milder cases, differences persisted after controlling for risk factors and mutation sites. These updated risk estimates should be used when counselling patients with CADASIL on prognosis.

Prevalence of epilepsy: a population-based cohort study in Denmark with comparison to Global Burden of Disease (GBD) prevalence estimates.

Neurology, Neurosurgery and Psychiatry

The Global Burden of Disease Study (GBD) produces prevalence estimates for 'idiopathic epilepsy' (ie, of unknown aetiology) and 'secondary epilepsy' (ie, with known aetiology) but does not report prevalence by underlying aetiologies for 'secondary epilepsy'.

We used nationwide, population-based register data from Denmark to identify underlying causes of epilepsy and their contribution to prevalence of 'secondary epilepsy' and compared with global prevalence data from GBD 2019. We identified all persons with a hospital-based epilepsy diagnosis and a filled prescription for antiseizure medication between 1 January 2009 and 31 December 2018. Epilepsy was categorised into 'idiopathic' or 'secondary' and 'total epilepsy' as the sum of the two epilepsy categories.

On 31 December 2018, a total of 5 784 284 individuals (49.7% males) were living in Denmark including 40 336 with epilepsy (51.5% males). Perinatal conditions, traumatic brain injury, brain tumours and stroke were prominent underlying causes of 'secondary epilepsy'. The prevalence of 'total epilepsy' in Denmark was 697 (95% CI 691 to 704) per 100 000 population (264 (95% CI 260 to 269) for 'secondary epilepsy' and 433 (95% CI 428 to 438) for 'idiopathic epilepsy'). In the GBD 2019 Study, the prevalence of 'total epilepsy' in 2018 was 682 (95% uncertainty interval (UI) 586 to 784) per 100 000 population (359 (95% UI 324-397) for 'secondary epilepsy' and 324 (95% UI 249 to 404) for 'idiopathic epilepsy').

Prevalence estimates of 'total epilepsy', 'idiopathic epilepsy' and 'secondary epilepsy' in Denmark align with the GBD 2019 estimates. In future studies, it is suggested to explicitly include all types of epilepsy, including 'secondary epilepsy', which is currently estimated as sequelae (consequences) of underlying diseases.

Codesign and evaluation of advanced therapeutic information resources for and with families of children with neurological conditions: a mixed methods cross-sectional study.

Cerebral Palsy

Parents and caregivers of children with neurological conditions express interest in new and developing treatments and trials; however, they have limited knowledge of, and access to, reliable information. This study aims to empower and equip decision-making and support communication in the application of advanced neurotherapeutics and personalised medicine, covering gene therapy, stem cell therapy, neurostimulation and neuroimmunotherapies.

Acceptability, Appropriateness, and Feasibility of Intervention Measures, Preparedness for Decision-Making Scale, Decision Self-efficacy Scale and open-ended qualitative feedback.

The resources provide an acceptable, appropriate, credible and feasible source of information. Parents also established they help with preparedness and confidence in decision-making regarding the applications of neurotherapeutics.

This study and its results are aligned with, and supports, the needs and preferences of caregivers of children with neurological conditions, promoting information provision, healthcare engagement and clinical decision-making. These resources will form a foundation for accurate and contemporary scientific knowledge that is distilled and available to a wide range of stakeholders.

Functional outcomes in children and adolescents with neurodisability accessing music therapy: A scoping review.

Cerebral Palsy

To determine the evidence for functional outcomes experienced by a population with paediatric neurodisability (such as acquired brain injury, cerebral palsy, spinal cord injury, and other neurological disorders), who access music therapy through neurorehabilitation services across the rehabilitation spectrum.

Using scoping review methodology of the JBI and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), a systematic search was conducted across eight databases and expert knowledge users were consulted. Articles were screened by title and abstract, and data from eligible studies were categorized using the International Classification of Functioning, Disability and Health: Children and Youth version (ICF-CY).

From 1726 records identified, 53 eligible primary sources were included in the synthesis. Most literature (n = 30) related to children and adolescents with an acquired or traumatic brain injury. Physical function was the most frequently reported outcome across sources (n = 27), followed by communication (n = 25), social (n = 22), cognitive (n = 17), emotional (n = 13), psychological (n = 13), behavioural (n = 8), and sensory (n = 5).

Evidence for functional outcomes experienced by children and adolescents accessing music therapy as part of their neurorehabilitation is limited. More than half of the included sources were clinical descriptions with small samples. High-quality studies involving children, adolescents, families, and interprofessional teams are needed to identify the most effective music therapy methods and techniques for functional outcomes in paediatric neurodisability.

e-EARLY TOGETHER Intervention for Infants at High Risk of Cerebral Palsy: Randomized Controlled Trial Protocol.

Cerebral Palsy

The purpose of this study is to evaluate the effectiveness of an early intervention program, e-EARLY TOGETHER, that combines goal-oriented training, parental coaching, environmental enrichment in a telehealth approach in a low- and middle-income country.

Protocol for a randomized controlled clinical trial to evaluate the effectiveness of e-EARLY TOGETHER intervention compared to standard guidelines on outcomes related to development and performance in infants at high risk of cerebral palsy.

This protocol will inform and enrich clinical practice related to early intervention in low- and middle-income countries. It is expected that the data obtained will contribute to the implementation of effective early intervention programs with positive and lasting results for the child, their family, and the community.

Brazilian Registry of Clinical Trials: RBR-7WWJRQ3, registered May 10, 2023; WHO Trial Registration UTN Code U-1111-1286-4639.

Predictors of school attendance among children with cerebral palsy in Bangladesh.

Cerebral Palsy

To determine school attendance and its predictors among children with cerebral palsy (CP) in Bangladesh using population-based data.

This study utilized data from the Bangladesh Cerebral Palsy Register (BCPR), a population-based register of children with CP aged less than 18 years in Bangladesh. Sociodemographic, clinical, and educational data were documented, and descriptive statistics and multivariate regression analyses were used to identify potential predictors of school attendance.

Between January 2015 and January 2019, 2725 children with CP were registered into BCPR of which 1582 were school-aged children (i.e. aged 6-18 years). The majority of those children had not attended school (73.9%); 50% (n = 239) children in Gross Motor Function Classification System (GMFCS) levels I to II did not attend schools. Adjusted odds ratios (OR) showed significantly higher odds of school attendance among children whose mothers had completed secondary education or higher (adjusted OR: 2.2; 95% confidence interval [CI]: 1.2-4.0) and received rehabilitation (adjusted OR: 2.1; 95% CI: 1.4-3.1). Conversely, lower odds of school attendance were observed among children aged 15 to 18 years (adjusted OR: 0.4; 95% CI: 0.2-0.8), those with bilateral CP (adjusted OR: 0.5; 95% CI: 0.3-0.8), GMFCS levels III to V (adjusted OR: 0.3; 95% CI: 0.2-0.5), Manual Ability Classification System levels III to V (adjusted OR: 0.5; 95% CI: 0.4-0.8), and speech impairment (adjusted OR: 0.3; 95% CI: 0.2-0.6).

A large number of children with CP in Bangladesh, including half of those with milder forms, do not attend schools. These findings underscore a deficiency in awareness and support, encompassing the provision of resources and trained teachers, highlighting the necessity for policy-level changes. Sociodemographic and clinical predictors should be taken into account when devising educational programmes to enhance school attendance for children with CP in Bangladesh.

The Role of Tissue Expansion Before Baclofen Pump Insertion in the Pediatric Population.

Cerebral Palsy

Tissue expansion is a well-established technique for soft tissue reconstruction in the pediatric population. We present a case series of this technique to create a safe pocket for baclofen pump insertion to minimize risk of complications including pump migration, extrusion, wound dehiscence and infection.

A case series of 3 pediatric patients undergoing tissue expansion prior to baclofen pump insertion at a single center in Melbourne. The expansion procedure was performed by senior surgeon N Low in all cases, and patients followed up 6 months after expander-pump exchange. The study was conducted over a 4-year period 2019 to 2023.

We suffered 2 minor complications with the tissue expansion process including cellulitis and pump deflation. Neither complication precluded further tissue expansion nor led to premature removal of the expander. All patients proceeded to safely complete expander-pump exchange. One patient suffered a small (6 mL) abdominal seroma associated with pump insertion, which required no intervention. All patients have had a successful outcome 6 months after pump insertion.

We describe a reliable and reproducible approach in creating a safe abdominal wall pocket to better accommodate baclofen pump insertion. Our series has overcome the imbalance between device size and abdominal wall pocket, now offering an alternative approach to achieve the safe delivery of intrathecal baclofen in the pediatric population.

Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration.

Neurology, Neurosurgery and Psychiatry

Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.

Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.

HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one ATXN1 expansion in a patient with HDPC.

The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.

Executive function in children with neurodevelopmental conditions: a systematic review and meta-analysis.

Cerebral Palsy

Executive function (EF) delays are well documented in paediatric neurodevelopmental conditions (NDCs). There is no consensus about whether EF delay...

Poor long-term outcomes and abnormal neurodegeneration biomarkers after military traumatic brain injury: the ADVANCE study.

Neurology, Neurosurgery and Psychiatry

Traumatic brain injury (TBI) is common in military campaigns and is a risk factor for dementia. ArmeD SerVices TrAuma and RehabilitatioN OutComE-TBI (ADVANCE-TBI) aims to ascertain neurological outcomes in UK military personnel with major battlefield trauma, leveraging advances in quantification of axonal breakdown markers like neurofilament light (NfL), and astroglial marker glial fibrillar acidic protein (GFAP) in blood. We aimed to describe the causes, prevalence and consequences of TBI, and its fluid biomarker associations.

TBI history was ascertained in 1145 servicemen and veterans, of whom 579 had been exposed to major trauma. Functional and mental health assessments were administered, and blood samples were collected approximately 8 years postinjury, with plasma biomarkers quantified (n=1125) for NfL, GFAP, total tau, phospho-tau181, amyloid-β 42 and 40. Outcomes were related to neurotrauma exposure.

TBI was present in 16.9% (n=98) of exposed participants, with 46.9% classified as mild-probable and 53.1% classified as moderate to severe. Depression (β=1.65, 95% CI (1.33 to 2.03)), anxiety (β=1.65 (1.34 to 2.03)) and post-traumatic stress disorder (β=1.30 (1.19 to 1.41)) symptoms were more common after TBI, alongside poorer 6 minute walk distance (β=0.79 (0.74 to 0.84)) and quality of life (β=1.27 (1.19 to 1.36), all p<0.001). Plasma GFAP was 11% (95% CI 2 to 21) higher post-TBI (p=0.013), with greater concentrations in moderate-to-severe injuries (47% higher than mild-probable (95% CI 20% to 82%, p<0.001). Unemployment was more common among those with elevated GFAP levels post-TBI, showing a 1.14-fold increase (95% CI 1.03 to 1.27, p<0.001) for every doubling in GFAP concentration.

TBI affected nearly a fifth of trauma-exposed personnel, related to worse mental health, motor and functional outcomes, as well as elevated plasma GFAP levels 8 years post-injury. This was absent after extracranial trauma, and showed a dose-response relationship with the severity of the injury.

Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis.

Neurology, Neurosurgery and Psychiatry

Immune-mediated processes are implicated in the pathogenesis of fatigue, a common symptom in multiple sclerosis (MS). The choroid plexus (CP) regulates central nervous system (CNS) immune homeostasis and undergoes volumetric modifications possibly contributing to MS-related fatigue. We explored the association between MS-related CP volume changes and fatigue dynamics.

Eighty-five patients with MS and 68 healthy controls (HC) underwent brain 3T MRI, neurological evaluation and Modified Fatigue Impact Scale (MFIS) at two timepoints (median follow-up=1.4 years). Normalised brain and regional grey matter (GM) volumes were obtained using FSL-SIENAx, FIRST, SIENA and tensor-based morphometry. CP volumes were quantified with in-house methods, and longitudinal changes were analysed using linear mixed models.

At baseline, 25 (29%) patients with MS had fatigue (f-MS) (MFIS ≥38). Compared with HC, patients with MS had significantly higher brain T2-lesion volume, lower brain, deep GM, cortical volumes and higher CP volume (false discovery rate (FDR)-p ≤0.024). Compared with non-fatigued (nf-MS) patients, f-MS were older, more disabled (FDR-p ≤0.002) and showed numerically higher CP volume (FDR-p=0.076). At follow-up, 41 (68%) nf-MS remained non-fatigued (nf-FU-MS) and 19 (32%) developed fatigue (f-FU-MS). Patients with MS showed higher brain and deep GM atrophy rates versus HC (FDR-p ≤0.048), whereas clinical, lesional and brain volumetric changes were not significantly different among MS groups (FDR-p ≥0.287). CP volume significantly increased in all MS groups compared with HC (FDR-p ≤0.043), with greater enlargement in f-FU-MS versus nf-FU-MS (FDR-p=0.048).

Larger CP and greater enlargement are associated with the presence and development of fatigue in MS, likely reflecting dynamic inflammatory states within the CNS, supporting the immunological contribution to MS-related fatigue.