BMJ Neurology Open最新文献

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.

Background and objective: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventral intermediate nucleus (Vim) is an effective therapy for medication-refractory essential tremor (ET). The Vim is not readily visualised on conventional MRI and targeting is routinely performed indirectly, with atlas co-ordinates. Inaccurate targeting due to interindividual anatomical variability can result in side effects and reduced efficacy. FAT1-weighted MRI is a high-resolution, high-fidelity modality that combines fractional anisotropy mapping and anatomical T1 sequences and allows direct visualisation of the Vim. Here, we assessed the outcomes of ET patients treated with a novel FAT1-weighted MRgFUS thalamotomy technique.

Methods: Targeting was performed through direct visualisation of the Vim on FAT1-weighted MRI sequence. Clinical, technical and imaging data were collected prospectively at baseline, 6 and 12 months follow-up.

Results: The first 14 consecutive ET patients undergoing MRgFUS at our centre were assessed. Their mean age was 73.6 years and disease duration was 31.8 years. There were significant improvements in treated hand tremor score (60%), disability score (71%) and quality of life (72%) and no clinically relevant side effects at 12 months. A mean of 6.9 sonications was performed and the mean time from first to last sonication was 34.6 min. Greater tremor improvement was observed with lesions in the inferior and lateral part of the Vim.

Conclusion: This is the first case series assessing FAT1-guided Vim targeting in MRgFUS thalamotomy. These results demonstrate that this method is safe and clinically effective, with added technical advantages including low sonication numbers and short procedural time.

Background: In a retrospective multicentre cohort study, we explored the association between brain atrophy and multiple sclerosis (MS) disability using different MRI scanners and protocols at multiple sites.

Methods: Relapse-onset MS patients were included if they had two clinical MRIs 12 months apart and ≥2 Expanded Disability Status Scale (EDSS) scores. Percentage brain volume change (PBVC), percentage grey matter change (PGMC), fluid-attenuated inversion recovery (FLAIR) lesion volume change, whole brain volume (BV), grey matter volume (GMV), FLAIR lesion volume and T1 hypointense lesion volume were assessed by icobrain. Disability was measured by EDSS scores and 6-month confirmed disability progression (CDP).

Results: Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. 93% of patients were on treatment and mean PBVC was -0.26% (±0.52). During the median follow-up of 2.8 years from the second MRI, median EDSS change was 0.0 and 12% patients experienced 6-month CDP. Cross-sectional BV and GMV at the later MRI showed a trend for association with CDP (HR 0.99; 95% CI 0.98 to 1.00; p=0.06). Only BV at the later MRI was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (β -0.001, SE 0.0003, p=0.02). There was no association between longitudinal PBVC or PGMC and CDP or EDSS (p>0.05).

Conclusion: In this highly treated MS cohort with low disability accrual, only cross-sectional BV showed an association with future EDSS scores, while no MRI metric predicted 6-month CDP. These findings highlight the limitations of current clinical MRI measures in predicting disability worsening in real-world settings.

Background: Dementia is a syndrome characterised by progressive cognitive and functional decline arising from a neurodegenerative disease. Genetic testing, imaging and fluid biomarkers mean that levels of risk of dementia diagnosis are becoming frequent and complex. How risk is communicated in this context is an increasingly important topic.

Aims: The aim of this scoping review is to map the existing literature regarding the components of risk communication, the factors influencing its outcomes and the guidelines developed to support clinicians in this process.

Methods: This is a systematic scoping review addressing the communication of risk to individuals living with or at risk of dementia, as well as perspectives of family, carers and healthcare professionals.

Results: 115 articles were identified, including genetic (n=41), amyloid (n=45) and other biomarkers (n=9). Patients expressed a desire to be informed about their risk of developing dementia, listing future planning and participation in clinical research as benefits of disclosure. While risk disclosure did not significantly impact anxiety or depression, it was associated with increased event distress among participants identified as elevated risk. Individuals at high risk frequently overestimated their likelihood of developing dementia. Tools and guidelines that have supported clinicians in risk disclosure emphasised the use of educational materials, clear communication about risk and prognosis, and regular follow-up appointments. Gaps in literature include blood biomarkers, non-Alzheimer's disease dementias and communication to people with cognitive impairment.

Conclusions: Risk communication is a crucial topic for healthcare professionals, especially since the emergence of novel techniques to predict dementia.

Background: Functional neurological disorder (FND) frequently co-exists with chronic pain (CP), notably nociceptive and nociplastic (primary) pain disorders. The considerable overlap implies shared underlying mechanisms because of their similar clinical and epidemiological profiles. Although standard neuroimaging and electrophysiological tests typically show normal results in both FND and primary pain disorders, recent advancements in neuroimaging techniques have begun identifying neural biomarkers common to both conditions, though these findings remain preliminary and require further exploration.

Method: We performed a detailed literature review of studies investigating neural activity in FND and chronic pain using electroencephalogram, magneto-encephalography, functional MRI, positron emission tomography and single photon emission computed tomography. Given the diverse nature of the reviewed studies, the synthesis is presented narratively.

Results: Despite methodological differences, convergent data suggest disrupted neural networks across both FND and CP. Common findings include (1) hyperactivation of sensorimotor networks, (2) altered activity within the default mode network-a critical region for self-referential thought-and (3) dysfunction in emotional processing regions, notably the anterior cingulate cortex and insula. Thalamocortical dysrhythmia was identified as a potential unifying concept, characterised by abnormal theta and beta oscillations that enhance pain perception in CP and trigger functional symptoms in FND. Both conditions also exhibit reduced alpha oscillations, likely amplifying sensory sensitivity and emotional responsiveness.

Conclusion: This review highlights shared neural abnormalities (Triple Network model) and introduces thalamocortical dysrhythmia as a novel explanatory framework linking FND and CP. Future research should target populations with coexisting disorders, potentially paving the way for innovative treatments, including hypnosis and neuromodulation/neurofeedback.

Background: Functional weakness is common, and the prognosis can be poor without treatment. Transcranial magnetic stimulation (TMS) and specialist physiotherapy have each been trialled separately as interventions for functional weakness. We tested a novel approach for treating functional weakness and gait disorder using TMS as a primer before specialist physiotherapy.

Methods: Single-pulse TMS, therapeutic education and limb pressure feedback were used as a primer for immediate specialist physiotherapy. TMS-primed physiotherapy was used for the first time in three consecutive patients with functional limb weakness and immobility.

Results: Two women and one man (aged 30-55 years) with severe functional limb weakness such that they were unable to stand or walk independently, with symptom duration between 3 weeks and 7 years, were studied. All three had a rapid return of voluntary limb movement and achieved unassisted walking within a few hours of a single TMS-primed physiotherapy session. Treatment was well-tolerated, and outcomes were sustained at follow-up.

Conclusions: These cases provide preliminary evidence supporting the efficacy of this approach, which may be further developed with future research. They also illustrate a practical approach for treating a clinically challenging population with severe functional weakness.

Objective: Atrial fibrillation (AF) is an important risk factor for cerebral stroke. We studied whether anticoagulation affected histological age aspects of thrombi retrieved from patients with AF-related stroke.

Methods: In this monocentric study, AF patients according to criteria (Trial of Org 10 172 in Acute Stroke Treatment) with occlusion of the middle cerebral artery were prospectively and consecutively included. They were assigned to three groups: anticoagulation naïve, adequately anticoagulated, and with paused anticoagulation. In addition to patient characteristics and stroke workup, extracted thrombi were histologically classified into different age categories according to their cellular to fibrotic transition.

Results: A total of 244 patients were studied, from which 136 (58 females; 78±9 years) were drug naïve, 34 (15 females; 78±8 years) had paused anticoagulation, and 74 (29 females; 79±9 years) were adequately anticoagulated. Groups did not differ regarding stroke severity at admission (modified Rankin Score, mRS: median, IQR: 5 (1); 5 (0.75); 5 (1), respectively; National Institutes of Health Stroke Scale (NIHSS): median, IQR: 16 (8); 16 (8); 16 (7), respectively). Due to thrombectomy, median scores declined in all groups without differences between groups (mRS: 3.5 (4); 4 (4); 4 (4); NIHSS: 5 (16); 11 (31); 7 (18)). With a small but significant effect (p=0.043), thrombus age differed between the groups due to significantly younger thrombi in the paused medication group as compared with the adequately anticoagulated patients.

Conclusions: Thrombus age distribution seems not to be affected by anticoagulation. The younger thrombi in patients with paused anticoagulation possibly point to a rebound effect needing further investigations.

Background: Evidence is scarce concerning the impact on postpartum relapse activity of disease-modifying therapy (DMT) use during pregnancy after assisted reproductive technology (ART) treatment. We investigated relapse activity before pregnancy, during pregnancy and 3 and 12 months postpartum overall and according to DMT exposure during pregnancy.

Methods: Women with relapsing-remitting multiple sclerosis (MS) from the Danish MS Registry who gave birth after ART from 1995 to 2018 were eligible for inclusion. Annualised relapse rate (ARR) before pregnancy, during pregnancy and postpartum was evaluated using a negative binomial regression model with relapse count as the dependent variable overall and according to DMT exposure during pregnancy. Logistic regression was used to identify predictors of being relapse-free 12 months postpartum.

Results: A total of 111 women, median age 32 years (IQR: 29-35), were included. Overall, ARR (95% CI) was 0.14 (0.08 to 0.24) before pregnancy, 0.13 (0.07 to 0.25) during pregnancy and 0.33 (0.17 to 0.61) 3 months postpartum; rate ratio difference between before pregnancy and postpartum was 2.42 (1.03 to 5.67), and between during pregnancy and postpartum was 2.46 (1.18 to 5.13). Age ≥35 years and no DMT exposure before pregnancy were predictors of being relapse-free 12 months postpartum.

Conclusions: Relapse activity was more than two times higher 3 months postpartum than before and during pregnancy. Stratified for DMT exposure during pregnancy, rate ratios were similar and did not reach statistical significance. Postpartum relapse activity more than doubled from both low ARR (unexposed to DMT during pregnancy) and higher ARR (exposed to DMT during pregnancy) pre-pregnancy.

Abstract:

Background: Given the increasing diversity among neurological patients, standardised protocols are essential for evaluating the severity and complexity of the variety of conditions. The aim of the present work was to standardise the assessment of the severity and complexity of neurological impairment in an acute setting by using a modified version of the Neurological Impairment Scale (mNIS).

Methods: Consecutively hospitalised neurological inpatients underwent a multidimensional standardised assessment of multimorbidity, frailty, functional dependency and neurological impairment using mNIS and other validated scales. Inter-rater reliability of the mNIS total and subscores was evaluated. Construct validity was assessed separately in patients with cerebrovascular disease, performing correlations between corresponding subscores of mNIS, original NIS and National Institutes of Health Stroke Scale. mNIS Complexity Index (mNIS-CI) for neurological severity was used to classify patients into subtle, mild, moderate and severe impairment.

Results: 1081 neurological patients admitted to a neurological ward from the emergency setting were enrolled. The inter-rater reliability was remarkable for mNIS total and subscores (intraclass correlation coefficient 0.90, 95% CI 0.82 to 0.95). The mNIS showed strong construct validity for total and subscores compared with other clinical scales (r 0.47-0.97, p<0.001) and 52.7% of patients scored at least one in one of the four newly listed items. The stratification of patients according to mNIS-CI exhibited high construct validity, distinguishing the extent of impairment and involved domains.

Conclusions: The mNIS is valuable for measuring neurological severity and complexity in acute inpatients and holds significant potential for application in different settings.

Background: Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND. This study confirmed positive signs of functional limb weakness (hereafter positive signs) in patients with long COVID.

Methods: This was an observational, retrospective, single-centre study at an outpatient clinic conducted from 1 June 2021 to 31 May 2024. We collected patients' clinical data, including positive signs. The primary outcome was the prevalence of positive signs. Patients with positive signs were followed up over 2 months, and subjective patient perceptions of symptomatic improvements and changes in positive signs were analysed.

Results: Overall, 502 were diagnosed with long COVID, and 100 assessed patients had positive signs. Female sex, time of infection after 2022, comorbidity of psychiatric diseases, fatigue, headache and muscle weakness were statistically significant in patients with positive signs compared with those in patients without positive signs. 89 patients (41 with positive signs and 48 without positive signs) were followed up, and 28 (68.3%) with positive signs and 33 (68.8%) without positive signs reported improvements. Positive signs disappeared in patients with symptomatic improvements but not in patients without symptomatic improvements (p=0.0001).

Conclusions: Positive signs were found in over one-third of patients (33.9%) who were investigated in this study. Some positive signs disappeared concurrently with their symptomatic improvement.