BMJ Neurology Open最新文献

Background Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system (CNS). Management during pregnancy is challenging due to limited safety data for disease-modifying therapies. Case presentation We report a case of a 41-year-old woman with aquaporin-4 (AQP4) IgG positive NMOSD who was switched from rituximab to ravulizumab during pregnancy. Ravulizumab was initiated shortly after conception and continued throughout pregnancy. Pregnancy was uneventful and she delivered a healthy term infant. At birth, umbilical cord blood testing revealed detectable ravulizumab levels and low C5 activity, confirming transplacental transfer of ravulizumab. The infant, now 4 months old, remains well. Conclusions This is the first reported case of ravulizumab use during pregnancy, with documentation of transplacental drug transfer and neonatal complement inhibition. Despite laboratory evidence of pharmacologic exposure, the neonate remained clinically well. These findings suggest that ravulizumab may be a viable treatment option for NMOSD during pregnancy when traditional agents are contraindicated or ineffective. However, further studies and longitudinal monitoring of exposed infants are essential to establish safety and clinical guidelines.

Background and objectives: Persistent headache has emerged as a symptom following acute COVID-19 and, to a lesser extent, after SARS-CoV-2 vaccination. However, the underlying mechanisms remain poorly understood. This study aimed to evaluate plasma levels of amyloid-related biomarkers in patients experiencing persistent headaches after COVID-19 or SARS-CoV-2 vaccination.

Methods: In this prospective observational cohort, patients presenting with severe headache as the dominating symptom after COVID-19 (n=29) or SARS-CoV-2 vaccination (n=31) had neurological assessments with reassessments after 6 months. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured using ELISA and compared with levels in healthy controls (n=16).

Results: We found a strong and persistent upregulation of APP in patients with headache after COVID-19 as compared with the two other groups. Notably, APP levels remained elevated at both inclusion and after 6 months in individuals with accompanying cognitive symptoms. In contrast, PZP levels were increased in patients with headache after SARS-CoV-2 vaccination at both time points relative to healthy controls. CTSL was only elevated in the post-COVID-19 at baseline, whereas SAA1 showed levels comparable across all groups.

Conclusion: Altered plasma levels of soluble markers, potentially reflecting changes in amyloid processing, were found in patients with persistent headache following SARS-CoV-2 vaccine, particularly in those with persistent headache after COVID-19. In the latter group, we also found some association with cognitive symptoms.

Trial registration numbers: NCT04576351 and NCT05235776.

Abstract:

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75^ECD) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.

Methods: This study measured urinary p75^ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75^ECD and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.

Results: Confirming previous findings, urinary p75^ECD levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75^ECD levels (Spearman's rho=-0.371, p≤0.0004, 95% CI (-0.543 to -0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75^ECD levels. There was a significant increase in p75^ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of -0.3).

Conclusions: Urinary p75^ECD is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker.

Background: Brachial plexopathies, including backpack palsy (BPP) and neuralgic amyotrophy (NA), are not uncommon in military populations. BPP is caused by compression or stretching of the brachial plexus, while NA is an inflammatory neuropathy potentially triggered by physical strain or infection. Previous studies suggest these conditions have significant incidence rates in military personnel, but further data are limited.

Methods: This prospective observational study tracked the incidence of BPP and NA among Dutch military personnel from 1 June 2022 to 1 January 2025. All patients with new symptoms of brachial plexopathy were included. Incidence was calculated using the total number of active military personnel during the study period. The incidence was calculated for different age categories.

Results: A total of 68 cases of BPP and NA were identified over the 31-month period. The calculated incidence of BPP and NA was 28.2 and 35.7 per 100 000 person-years, respectively. BPP was most common in soldiers under 25 (89.6 per 100 000 person-years), while NA was more evenly distributed across age groups.

Conclusions: This study confirms a high incidence of plexopathies in the Dutch military population, particularly BPP in younger soldiers. These findings underscore the need for targeted prevention strategies to maintain operational readiness.

Background: The burden and profile of intracranial atherosclerotic stenosis (ICAS) among Asians remain incompletely understood. We aimed to describe and review the current body of literature on the prevalence of ICAS, its frequency among patients with ischaemic stroke and its associated risk factors across different Asian populations, taking into account the diagnostic modalities and criteria used to identify ICAS in these studies.

Methods: We performed a systematic scoping and rapid review of published studies reporting on the prevalence, frequency in ischaemic stroke and risk factors associated with ICAS in Asian populations.

Results: Of the 1272 identified citations, 142 were included in the final review: 54 studies reported on prevalence, 56 on frequency in ischaemic stroke and 120 on risk factors. Most studies were conducted in China, Hong Kong, Korea and Japan. Reported ICAS prevalence varied widely, from 3% to 89.4% (median 13%), while frequency in ischaemic stroke ranged from 7.9% to 82.4% (median 41.65%). Magnetic resonance and transcranial ultrasonography were the most frequently used diagnostic modalities, with most studies applying a ≥50% stenosis threshold. Associations between ICAS and traditional (eg, age, hypertension, diabetes, dyslipidaemia, smoking and prior stroke), genetic and other emerging risk factors were reported, although the strength and consistency of associations varied.

Conclusion: Our review supports the prevailing understanding of a relatively higher burden of ICAS among Asians, while also underscoring the substantial heterogeneity in reported prevalence and frequency in ischaemic stroke of ICAS across Asian populations. Variability in diagnostic modalities and criteria used to identify ICAS likely influenced these rates. While a range of risk factors has been identified, the strength and consistency of associations vary. The concentration of studies in East Asia underscores the need for further research, particularly in under-represented countries. The standardisation of diagnostic criteria and imaging protocols for ICAS is needed.

Registration: https://doi.org/10.17605/OSF.IO/PKVJ3.

Introduction: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Hyperintense signals on diffusion-weighted imaging (DWI) at the corticomedullary junction are key diagnostic features. Early manifestations are often overlooked, leading to misdiagnoses. Here, we report a case of adult-onset NIID with DWI hyperintensities at the corticomedullary junction.

Case presentation: A 72-year-old woman presented with progressive memory deterioration starting 9 years ago. In the third year, MRI showed extensive white matter lesions and brain atrophy, with focal high signal intensity in the corticomedullary junction of the frontal lobe; however, this was overlooked. The patient was clinically diagnosed with Alzheimer's disease. In the seventh year, the patient gradually developed emotional instability, bradykinesia and urinary incontinence. In the eighth year, MRI revealed a remarkable curvilinear DWI hyperintense signal at the corticomedullary junction. Further genetic testing identified 105 GGC repeats in the NOTCH2NLC gene. Skin biopsy revealed intranuclear inclusions in P62 and ubiquitin-positive fibroblasts, confirming the NIID diagnosis.

Conclusions: Patients with NIID show characteristic DWI hyperintensity at the corticomedullary junction during symptoms. This early imaging finding is subtle and often overlooked. For patients with dementia and episodic encephalopathy, observing radiological changes, along with genetic and skin biopsies, is indispensable.

Background: The aetiologic identification of central nervous infections, including Listeria, remains challenging as most pathogens are not identified in meningoencephalitis cases despite advances in molecular diagnostics. Plasma next-generation sequencing (NGS) has exciting potential in the clinical setting due to the broad detection range and non-invasive testing approach.

Case presentation: A 59-year-old non-binary and healthy individual presented with fever and vomiting. They were found to have nystagmus, dysphagia and hypophonia. Their course was complicated by progressive encephalopathy, thus requiring intubation. Serial brain MRIs performed days apart demonstrated rapidly progressive cerebral oedema and expanding ring-enhancing brain abscesses. Extensive diagnostic testing was unrevealing, which included multiple PCR cerebrospinal fluid (CSF) infectious tests and both dedicated serum and CSF serological testing for neuroinflammatory aetiologies. Given the rapid and significant clinical deterioration, the patient underwent plasma NGS testing and a brain biopsy. Listeria was ultimately detected with NGS multiple days before the biopsy results were available.

Conclusions: This is one of the first reported cases of diagnosing Listeria in the central nervous system with plasma NGS, rather than CSF, testing. This case describes the potential to improve a patient's clinical outcomes using plasma NGS in situations of diagnostic uncertainty or high-risk biopsies.

Background: Obstructive sleep apnoea (OSA) is associated with adverse health outcomes. However, the association with dementia remains uncertain. Thus, we examined the association of OSA with all-cause dementia and Alzheimer's disease.

Methods: We conducted a Danish nationwide population-based cohort study using health registries. Patients with OSA were identified from 1995 to 2017. Furthermore, a propensity score-matched comparison cohort was defined. Propensity scores were computed based on age, sex, comorbidities and education. With follow-up until 2018, we computed incidence rates (IRs) and HRs for all-cause dementia and Alzheimer's disease. Subgroup analyses were conducted by sex, age, overweight/obesity, hypertension and continuous positive airway pressure (CPAP) treatment.

Results: We identified 62 928 patients with OSA and 62 928 in the propensity score-matched comparison cohort (76% male, median age 52 years). The IR for all-cause dementia was 1.27 (95% CI 1.17 to 1.37) per 1000 person-years in patients with OSA and 1.15 (95% CI 1.05 to 1.25) in the propensity score-matched comparison cohort, yielding an HR of 1.10 (95% CI 0.98 to 1.24). The HR for Alzheimer's disease was 1.16 (95% CI 0.94 to 1.43). Among individuals with overweight/obesity, the HR for all-cause dementia was 0.71 (95% CI 0.51 to 0.99), while it was 1.17 (95% CI 1.03 to 1.33) in those without. CPAP treatment attenuated associations.

Conclusion: Our findings support a modest association between OSA and dementia, including Alzheimer's disease, motivating early clinical detection of OSA as a potentially modifiable risk factor for subsequent dementia. The finding that the dementia hazard was not increased in the setting of overweight or obesity requires further study and points to the need for research on mechanisms underlying the association between OSA and dementia.

Background: Parkinson's disease (PD) is primarily characterised by parkinsonism due to nigro-striatal dopaminergic denervation. While therapeutic strategies have traditionally focused on compensating for dopaminergic deficit, growing evidence reveals an involvement of cholinergic and glutamatergic pathways in the pathogenesis of the motor and non-motor manifestations of the disease. The purpose of this review is to provide an overview of the efficacy of cholinesterase inhibitors (ChIs) and memantine (glutamate receptor antagonist) in patients affected by PD without dementia on motor (gait, balance) and non-motor (cognitive, behavioural, sleep and autonomic) symptoms usually poorly responsive to levodopa.

Methods: A systematic review of randomised controlled trials (RCTs) was conducted. The search was performed on PubMed, Cochrane Library and Embase databases for articles published between January 1996 and October 2024, using predefined inclusion and exclusion criteria. Risk of bias was assessed with the Cochrane Risk of Bias tool. Results are presented narratively.

Results: 12 RCTs were included in this review, with 10 (774 patients) focusing on ChIs and 2 (65 patients) on memantine. Some studies highlighted the beneficial effects of ChI on mild cognitive impairment and suggested potential improvements in apathy and gait disturbances. However, the findings regarding the impact of ChI and memantine on other non-motor symptoms were inconsistent.

Conclusions: Available RCTs suggest that ChIs may have a valuable role in managing cognitive impairment, apathy and gait disorders in PD patients without dementia. However, due to the lack of strong evidence, a cautious and individualised approach is advisable when considering these treatments.Cite Now.

Introduction: Myasthenia gravis (MG), an IgG-mediated autoimmune disorder targeting neuromuscular junctions, shows refractory in 12-20% of generalised MG (gMG) patients despite immunotherapies. Plasma exchange (PLEX) transiently depletes pathogenic mediators, while neonatal Fc receptor antagonists (eg, efgartigimod) offer novel therapeutic potential. Both PLEX and efgartigimod require adjunctive non-steroidal immunosuppressive therapy (NSIST) for sustained remission. This study aims to evaluate the effectiveness and safety of efgartigimod working as a bridge treatment after PLEX but before NSIST taking effect, while concurrently conducting a comparative analysis of clinical outcomes between PLEX and efgartigimod in gMG.

Methods and analysis: This multicentre, open-label, three-arm trial (n=45 gMG patients) assigns cohorts to PLEX+efgartigimod, PLEX alone or efgartigimod alone. The intervention comprises PLEX and/or efgartigimod. Oral glucocorticoids and cholinesterase inhibitors are allowed during this study. NSIST starts the day after completing PLEX or the second dose of efgartigimod. Outcomes are assessed at weeks 4, 8, 12, 16, 20, 24, 36 and 48. Primary endpoint: proportion achieving minimal symptom expression (MSE) at week 48. Secondary endpoints: median time to first MSE, adverse events (AE) incidence/severity, exacerbation rates, neurological functional assessment scores, cholinesterase inhibitor/corticosteroid usage, serological evolution of immunological markers. All AEs are systematically documented and causality-assessed.

Ethics and dissemination: Ethical clearance for this investigation was granted by the Institutional Review Board of Punan Hospital in accordance with Declaration of Helsinki principles. All enrolled participants will provide written informed consent through standardised documentation processes prior to study enrolment. The results will be accessible in peer-reviewed publications.

Trial registration number: ChiCTR2500104662.