BMJ Neurology Open最新文献

Over the long term, Parkinson's disease (PD) appears to progress, in a linear fashion, at an annual rate of about 2% of the maximum motor disability score. This figure aligns quite well with pathological research on the rate that substantia nigra dopaminergic neurons are lost. An unexpected finding from cohort studies and clinical trials is that progression is twice as fast in prodromal PD, leading up to clinical diagnosis, and in recently diagnosed PD prior to the commencement of dopaminergic therapy. Levodopa initiation reduces motor disability by 40% of the pretreatment level. This benefit is composed of the short duration response, which is easily measured as the difference between on and off states, and the long duration response, which is comparable in size though not directly observable. Despite clinical impressions to the contrary, there is little evidence that the response to levodopa wanes over time or that axial motor deficits affecting speech, gait and balance become increasingly resistant to treatment. While not revealed by prospective longitudinal studies, the advanced PD phase, accompanied by visual hallucinations and cognitive decline, may show an exponential rate of change. Serial motor scale assessment, informed by a knowledge of symptomatic dopaminergic treatment effects, is probably still the best way to measure the underlying rate of progression of PD in clinical trials.

Background: Nitrous oxide (N₂O)-related neurotoxicity is a significant public health concern among young people in the UK. Recognition necessitates timely diagnosis, abstinence from N₂O consumption and replacement of vitamin B12, usually via intramuscular (IM) hydroxocobalamin. This service development project evaluated a self-injection programme (SIP) compared with a nurse-led approach, within an established ambulatory care pathway, with the aim of improving treatment adherence and completion.

Methods: Between June and December 2024, a total of 46 patients presenting with N₂O-induced neurological symptoms were included in the evaluation. Patients were given the choice of self-injecting (SIP, n=25) or attending the hospital for nurse-led administration (non-SIP, n=21). Clinical outcomes, adherence and functional improvement (including the 10 metre walk test (10MWT)) were assessed.

Results: Most patients were young (median age of 23), male (n=29, 63%), of Asian or Asian British ethnicity (n=29, 63%), and regularly using N₂O (n=32, 70%). SIP patients had higher adherence, missing fewer IM B12 doses compared with non-SIP (79.7% vs 20.3%, p<0.001). Clinical recovery rates were comparable, with 74% achieving full or substantial improvement across both groups. Walking speed (10MWT) improved across both groups following treatment and did not differ between groups.

Conclusion: Self-injection of IM hydroxocobalamin is a feasible and likely cost-effective alternative to nurse-led administration while maintaining clinical efficacy.

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.