BMJ Neurology Open最新文献

Abstract:

Introduction: People with Parkinson's disease (PwPD) experience a wide range of motor and non-motor symptoms that have a significant impact on their health and quality of life. Effective care management for PwPD involves monitoring symptoms at home, involving specialised multidisciplinary care providers and enhancing self-management skills. This study protocol describes the process evaluation within a randomised clinical trial to assess the implementation and its impact on patient health outcomes of ParkProReakt-a proactive, multidisciplinary, digitally supported care model for community-dwelling PwPD.

Methods and analysis: The hybrid efficacy-implementation study will assess key implementation outcomes using the Medical Research Council framework for complex interventions alongside a randomised controlled trial. A combination of quantitative and qualitative methods will be used to assess process data from care providers and patients. The main process outcomes are fidelity, dose, feasibility and context. Context will be analysed through semistructured interviews and focus groups using the Consolidated Framework of Implementation Research. To elucidate potential facilitators and barriers to implementation and to gain deeper insights into the efficacy outcome data, quantitative and qualitative process data will be integrated at an interpretative level using mixed methods. In addition to process evaluation, potential indirect mechanisms of impact will be measured.

Ethics and dissemination: Ethical approval for this study was obtained from the responsible state medical ethics committees in Hesse and Hamburg, Germany. Results will be communicated to the funding body and disseminated through scientific publications.

Trial registration: This study was registered with the German Registry for Clinical Studies (DRKS)-number: DRKS00031092.

Introduction: Myasthenia gravis (MG) is a T cell-dependent B cell-mediated autoimmune disease with pathogenic antibodies directed against components of the acetylcholine receptor (AChR). Current therapies do not address the root cause of the disease (autoimmune recognition of AChR) and are associated with possible serious side effects. Therefore, new therapeutic options targeting antigen-specific autoimmunity are needed. COUR nanoparticle (CNP-106) is an antigen-specific immune tolerance therapy directed to the AChR to stop the pathogenic driver of MG. Data from experimental models suggest the potential benefit of CNP-106 to patients by reprogramming the immune system to AChR and stopping the progression of the disease. The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.

Methods and analysis: The outlined study is a multicentre Phase 1b/2a double-blind, randomised, placebo-controlled trial with an enrolment target of 54 AChR antibody-positive generalised MG subjects. The primary endpoint is safety and tolerability. Exploratory and secondary endpoints include disease-specific clinical scores, measures of quality of life and activities of daily living, antigen-specific T cells and AChR antibodies. Trial enrolment is anticipated to start in 2024.

Ethics and dissemination: The trial has ethical approval from the Central Institutional Review Boards and has clinical trial authorisation from the Food and Drug Administration. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals.

Trial registration number: NCT06106672.

Introduction: Ischaemic stroke, primarily caused by thromboembolic events, typically arises as a consequence of underlying vascular or cardiac pathology. Non-thrombotic embolic strokes, although rare, are increasingly seen in interventional and intravascular procedures. Oxygen-ozone therapy (OOT) is one of the popular treatments for lumbar disc herniation, providing pain relief. However, it has been linked to gas embolisms, posing severe risks. This article details a case of cerebral gas embolism and multifocal acute ischaemic stroke that occurred during OOT for lumbar disc herniation pain relief.

Case presentation: We present a case of a 58-year-old woman with acute onset limb weakness and speech disturbance that happened during a lumbar intradiscal oxygen-ozone injection session. Brain CT and MRI scans showed multiple cerebral gas embolisms and diffusion-restricted areas in both cerebral hemispheres. Echocardiography revealed a patent foramen ovale, hinting at a conduit for paradoxical embolism. Follow-up of the patient after 1 year showed significant improvement.

Conclusion: OOT, as a popular treatment for chronic pain, has been associated with severe adverse events. When facing cases of acute postoperative or postinterventional encephalopathy or stroke, arterial cerebral gas embolism should be considered a possibility. The presence of intracardiac defects or intrapulmonary shunts paves the way for paradoxical emboli to happen, resulting in a higher chance of neurological complications.

Objective: The objective of this study is to identify factors influencing progression of respiratory decline from the onset of neurological symptoms to respiratory failure in patients with amyotrophic lateral sclerosis (ALS).

Methods: In 100 patients with sporadic ALS, %vital capacity (%VC) was continuously measured from the first visit to the respiratory endpoint (REP). Cox proportional hazards model identified factors influencing the duration from onset of ALS to REP (Onset-REP). We performed Kaplan-Meier survival curve analysis for onset-REP according to identified factors.

Results: Onset sites were the upper limb (U-ALS), lower limb (L-ALS), bulbar paralysis (B-ALS) and respiratory paralysis (R-ALS) in 37, 19, 32 and 12 patients, respectively. Duration from the onset of ALS to the onset of respiratory symptoms (Onset-Rp) and REP (Onset-REP) was 16.1 (SD 12.1) and 24.9 months (SD 14.6), respectively. Multivariate analysis revealed that age at onset, site of onset, Onset-Rp and %VC decline rate significantly influenced Onset-REP duration. Elderly patients had a significantly shorter Onset-REP duration. Onset-REP duration did not significantly differ between patients with U-ALS and L-ALS, but was longer in these patients than in those with B-ALS and R-ALS. Onset-REP duration was positively associated with Onset-Rp duration. The average monthly %VC decline rate was -5.6% (SD 3.3). Age at onset, onset site and Onset-Rp duration significantly influenced the %VC decline rate.

Conclusions: Our findings revealed strong and independent patient-specific factors that influence the Onset-REP duration and the %VC decline rate in patients with ALS. These could inform future clinical trials and interventions considering the respiratory function and natural history of patients with ALS.

Background: Dimethyl fumarate (DMF) is increasingly used in treating multiple sclerosis (MS) with controversial results of the safety and efficacy of different DMF doses. We aimed to systematically review the literature to examine the safety and efficacy of DMF for MS patients.

Methods: We searched PubMed Medline, Cochrane, Web of Science, Scopus databases and clinicaltrials.gov up to June 2023 for the published trials evaluating the use of DMF for MS in adults. All included studies were screened and abstracted independently by two authors. Efficacy and safety outcome measures were extracted. The meta-analysis was conducted using Review Manager 5.4.

Results: 10 studies including eight randomised controlled trials, one open-label and one single-arm before-after study with a total population size of 4278 patients were included. DMF group showed a statistically significant reduction in the proportion of relapses compared with the control group, (OR: 0.47, 95% CI: [0.41, 0.55], p<0.00001) with no statistical differences between 240 mg two times per day and three times a day doses. Furthermore, the DMF group had a significant reduction in Gd-enhanced lesions compared with control (MD=-1.53, 95% CI: [-1.91 to -1.41], p<0.00001). Our results showed a non-significant difference in adverse events that led to discontinuation of the study with an OR of 1.29 (95% CI: [0.98, 1.71], p value=0.07).

Discussion: DMF had significant efficacy and safety compared with the control, with no difference between the DMF doses. More studies with large sample sizes and longer follow-ups are needed to detect long-term safety and efficacy.

Objectives: Survivors of intracerebral haemorrhage (ICH) are at high risk of incident depression, which is modified by social determinants of health (SDOH) and associated with worse functional outcomes. We sought to determine the role of prestroke SDOH in depression incidence after ICH to better characterise post-ICH outcomes.

Study design: We analysed data from a cohort study of ICH survivors without prestroke depression, presenting at Massachusetts General Hospital between 2006 and 2017. We collected information from electronic health records (EHR), follow-up interviews and CT/MRI. The relationship between social vulnerability, air quality and post-ICH depression incidence within 12 months of acute haemorrhage was investigated using logistic regression models that also included EHR and CT/MRI information as predictors.

Results: Participants were 576 survivors, median age of 72 (IQR=61-81), 317 (55%) self-reported as male and 482 (84%) as white. 204 (35%) were diagnosed with depression within 12 months of ICH. Hospital admission longer than 1 week (OR 1.80, 95% CI 1.08 to 3.00), cerebral amyloid angiopathy (CAA) burden (OR 1.45, 95% CI 1.25 to 1.68) and social vulnerability (OR 3.03, 95% CI 1.49 to 6.19) were associated with depression incidence post-ICH.

Conclusions: In addition to CAA burden and patient location 1-week post-ICH, social vulnerability was independently associated with depression among ICH survivors. Our findings suggest that social vulnerability influences ICH outcomes. Future studies should investigate how poststroke clinical care interventions can address SDOH effects to reduce incident depression and improve outcomes among ICH survivors.

Background: Spinal cord infarction (SCI) is associated with poor clinical outcome. Intravenous thrombolysis (IVT) is a well-established treatment for cerebral ischaemic stroke. However, its efficacy in SCI is unknown.

Objective: We present a case of acute spinal cord ischaemia with significant improvement following thrombolysis and review the current literature to explore the safety and feasibility of this treatment.

Methods: We reviewed the literature for cases of SCI that were treated with IVT. We reviewed their medical history, clinical presentation and the reported outcome.

Results: Other than our case, our review includes 19 cases of SCI treated with IVT. Their mean age was 62.87±15.27 and 36% of them were women. Most of the cases were spontaneous and treated within 240 min of onset. Favourable outcome was achieved in 89% of cases, including the few cases treated within extended time window. No clinical worsening due to haemorrhage was reported in either case.

Conclusions: IVT may be considered in certain settings as treatment for SCI following the appropriate work-up. Favourable outcome was achieved in most cases and no case experienced clinical worsening due to post-thrombolysis haemorrhage. Safety and efficacy of this approach need further investigation.

Background: Pain is a serious manifestation in both the acute and chronic stages of Guillain-Barre syndrome (GBS). We evaluated the frequency, characteristics and associated factors of pain and its impact on quality of life (QoL) among patients with GBS.

Methods: We enrolled 644 patients with GBS from prospective cohort studies in Bangladesh conducted between 2010 and 2024. Data were collected at enrolment and at standard follow-up time points up to 26 weeks. Pain intensity was measured by a pain numeric rating scale. Group differences were tested using the χ² or Fisher's exact test, longitudinal changes were analysed with repeated-measures analysis of variance and correlations were analysed with Spearman's rank test.

Results: The median age of the patients was 31 years, with 70% men. During enrolment, 71% of patients reported pain, which persisted among 38% at week 13 and 26% at week 26. Pain was significantly associated with disease severity, muscle weakness and treatment with intravenous immunoglobulin in both the acute and chronic stages. Patients with acute pain had a higher proportion of axonal GBS (p=0.000) than those without pain. Chronic pain was associated with higher age (p=0.006), male sex (p=0.000), preceding diarrhoea (p=0.033) and dysautonomia (p=0.000). Higher pain intensity was reported among women (p=0.027), patients with higher age (p=0.029) and severe form of GBS (p=0.038) compared with counter groups. Acute pain was significantly associated with the 'self-care' (p=0.023), 'usual activities' (p=0.049) and 'anxiety/depression' (p=0.048) domains of QoL, whereas chronic pain was associated with the 'anxiety/depression' (p=0.005) domain.

Conclusions: Pain presented as a serious symptom negatively affecting the QoL in GBS. Systematic evaluation of pain is recommended to ensure a personalised treatment approach for GBS.

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory condition characterised by demyelination and axonal damage in the central nervous system. Diffusion tensor imaging (DTI) enables non-invasive investigation of microstructural white matter alterations, while serum neurofilament light chain (NFL) holds promise as a fluid biomarker of axonal injury.

Objectives: To use DTI and serum NFL measurements to evaluate white matter pathology in patients with MS and explore the relationship between in vivo imaging and biochemical indicators of axonal damage.

Methods: 41 patients with relapse-remitting MS and 41 age-matched healthy controls underwent brain MRI including DTI acquisition. Serum samples were analysed for NFL concentrations using ELISA. Region of interest analysis was conducted to derive DTI metrics including fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity. Correlational analyses were used to explore the associations between the imaging and biochemical indices.

Results: Patients exhibited significantly elevated serum NFL levels and altered DTI metrics compared with controls, indicative of axonal/myelin pathology. DTI parameters were positively correlated with serum NFL concentration (p value<0.0001). Visual analogue scale scores demonstrated a significant positive relationship between DTI metrics and NFL, validating their potential as radiological and fluid-based markers of symptom severity.

Conclusions: Combined DTI and serum NFL measurements may enhance the evaluation of axonal injury in MS by providing complementary in vivo and biochemical perspectives. The corresponding changes observed between the modalities support their utility as non-invasive biomarkers reflecting pathophysiological processes and clinical status in MS. Larger validation cohorts are needed to determine the clinical applicability.

Objective: We examined the presentation to hospital, subtypes of ischaemic stroke for patients admitted to stroke services in Qatar and their 90-day prognosis based on the modified Rankin Scale (mRS) for those with diagnosed and undiagnosed diabetes, hypertension and dyslipidaemia.

Methods: We conducted a retrospective analysis of patients admitted with acute ischaemic stroke from January 2014 to April 2024. The mRS was dichotomised with favourable outcome (0-2) and unfavourable outcome (3-6).

Results: A total of 9479 patients were included in the study. Patients with a prior history of hypertension and dyslipidaemia and untreated/undiagnosed for these risk factors on admission were more likely to present with a lower National Institute of Health Stroke Scale (NIHSS) score at admission (p<0.001). These patients were also more likely to present with small vessel disease (SVD) or subcortical stroke (p<0.001). Multivariate analysis revealed that age (adjusted OR 1.05, 95% CI 1.04 to 1.06) and hypertension (adjusted OR 1.44, 95% CI 1.07 to 1.96) were more likely to have an mRS score of 3-6 at 90 days while males (adjusted OR 0.56, 95% CI 0.46 to 0.69), prior antidiabetic therapy (adjusted OR 0.52, 95% CI 0.34 to 0.79) and undiagnosed diabetes (adjusted OR 0.46, 95% CI 0.22 to 0.99) were protective against an mRS score of 3-6 at 90 days after adjusting for covariates.

Conclusion: Patients with a prior history of hypertension and dyslipidaemia and undiagnosed on admission are more likely to present with a lower NIHSS score but have a worse outcome at 90 days. The lower NIHSS may be explained by a higher frequency of SVD.