Therapeutic Advances in Neurological Disorders最新文献

Background: Anti-Yo antibodies, which target the onconeural antigen cerebellar degeneration-related 2-like (CDR2L), have been only sporadically reported in patients with post-immune checkpoint inhibitor (post-ICI) neurological syndromes.

Objectives: To analyze the clinical and tumor features of patients with post-ICI anti-Yo neurological syndromes identified in a national reference center.

Design: Retrospective observational study.

Methods: All patients with post-ICI neurological syndromes and anti-Yo antibody positivity confirmed in a national reference center (2019-2024) were included. Comparative genomic hybridization array, immunohistochemistry against CDR2L, and analysis of Yo immunoreactivity using biotinylated anti-Yo sera were performed on the available tumor samples.

Results: In the five patients (4/5 female, median age 61 years) included, the neurological syndrome occurred after a median of 2 cycles of PD1 inhibitor. Four patients developed a rapidly progressive cerebellar syndrome (RPCS), while one presented with myelitis. All cases were severe (modified Rankin scale score 4-5) and did not improve with treatment. Cancer types were lung adenocarcinoma (2/5), endometrial serous carcinoma (2/5), and ovarian clear cell carcinoma (1/5). Anti-Yo antibodies were retrospectively detected before ICI initiation in one patient with RPCS and an ovarian tumor. This tumor showed a gain in the CDR2L locus, CDR2L overexpression, and Yo immunoreactivity with biotinylated anti-Yo sera, similar to ovarian tumors from patients with spontaneous anti-Yo paraneoplastic neurological syndrome. By contrast, CDR2L was not overexpressed in the lung tumor from one patient with myelitis, which nevertheless had a strong immunoreactivity with anti-Yo sera, absent in the control lung tumor.

Conclusion: Post-ICI anti-Yo neurological syndromes may occur with atypical cancer associations, but mostly manifest with a RCPS indistinguishable from spontaneous anti-Yo paraneoplastic neurological syndromes, suggesting a similar immune-mediated attack on the cerebellum. The CDR2L antigen overexpression and the pre-ICI anti-Yo antibody positivity in the patient with ovarian cancer suggest that the ICI boosted a pre-formed, tumor-driven anti-Yo autoimmunity. Further studies are needed to clarify whether this mechanism applies to all patients and if other types of tumor alterations and/or immune dysfunctions could be involved.

Background: Subcutaneous natalizumab (scN) was recently approved in Argentina for people with multiple sclerosis (pwMS). The impact of this change in this population is unknown.

Objectives: To evaluate the use, access and satisfaction of scN and correlate it with clinical and demographic variables. Desing: cross-sectional study was conducted, surveying pwMS who received scN and ivN from public and private MS Centres since its approval.

Methods: Treatment adherence was assessed using the MS Treatment Adherence Questionnaire (MS-TAQ) and satisfaction using Treatment Satisfaction of Questionnaire for Medication (TSQM). Clinical and demographic variables were also recorded. Results: 84 pwMS were included, 58.3% female, mean EDSS: 2.4 ± 1.2, mean age: 34.8 ± 10.8 years, mean disease duration: 7.8 ± 4.5 years, mean time under N: 43.7 ± 28.7 months, 45.2% naïve of prior disease modifying treatments, 77.4% (n = 65) under scN (60.7%, n = 51 are switchers from ivN, 49% due to difficult access to an infusion centre); and 22.6% 8 (n = 19) under ivN. The main barrier for change from iv to sc was the refusal from health insurance. Of the total of pwMS, 42% (n = 36) had a delay or lack of at least one dose from their social insurance, all from public hospitals. We found an association between scN use and high scores on the convenience items of TSQM (p < 0.0001, X ² = 74), unlike ivN. Regardless of route of administration, most of pwMS showed high percentages of satisfaction in the effectiveness and global satisfaction items, without differences between ivN and scM.

Conclusion: We found a high rate of change to scN from ivN, associated with a higher score in the comfort and convenience items in people receiving scN, compared to ivN. Access barriers should be addressed in order to improve treatment comfort.

Pediatric-onset multiple sclerosis (POMS), accounting for ~5% of all MS cases, is a chronic immune-mediated demyelinating disorder of the central nervous system. Relapse prevention remains a challenge, and B cells play a central role in the pathogenesis. Ofatumumab (OFA), a fully human anti-CD20 monoclonal antibody, is approved for adult MS. To assess the safety and efficacy of off-label OFA use in pediatric MS patients. We retrospectively analyzed clinical data from four pediatric patients with MS who received OFA. Retrospective case series. Four pediatric MS patients received OFA as disease-modifying treatment at ages ranging from 9.7 to 12.8 years for durations between 6 and 20 months. Three patients received OFA treatment for uncontrolled relapses, while one switched from rituximab. After the initial treatment phase of OFA, B-cell depletion was achieved in three patients, and this depletion was not consistently maintained throughout the maintenance phase. All patients remained relapse-free, with no new or enlarging T2 lesions or contrast-enhancing lesions observed on MRI or EDSS progression. The annual relapse rate after OFA treatment decreased compared with that before OFA treatment. One patient reported mild adverse events, including transient fever and atopic dermatitis, all of which were manageable. Ofatumumab showed favorable tolerability and potential benefit in this small pediatric MS cohort. Its subcutaneous administration offers practical advantages. While these findings suggest feasibility, the limited evidence precludes clinical recommendation at this stage. Larger prospective studies are warranted.

Background: Detection of atrial fibrillation (AF) after ischemic stroke (IS) is crucial for starting anticoagulant therapy to prevent IS recurrence. Strategies to identify patients who might benefit the most from extended electrocardiography (ECG) monitoring would be highly desirable.

Objectives: We aimed to investigate the role of brain natriuretic peptide (BNP) and echocardiographic parameters as biomarkers for predicting new AF detection in a large cohort of patients with acute IS.

Design: We retrospectively analyzed data of 2411 consecutive patients admitted for IS to a single Stroke Center from January 1, 2018, to May 31, 2023.

Methods: BNP levels were measured within 48 h of onset. Clinical and echocardiographic variables were evaluated. Single or multiple 12-lead ECG and continuous monitoring with external or implantable devices were used to detect new AF. The outcome measure was new AF detection at 3 months.

Results: Of 2337 included patients, 1907 (81.6%) had not previously known AF, and new AF was detected in 422 (22%) patients. In the multivariate analysis, older age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02-1.05, p < 0.001), higher National Institutes of Health Stroke Scale score (OR 1.05, 95% CI 1.03-1.07, p < 0.001), BNP ⩾150 pg/ml (OR 4.10, 95% CI 2.95-5.69, p < 0.001), and left atrium (LA) enlargement (OR 2.88, 95% CI 1.99-4.18, p < 0.001) were independently associated with new AF detection. The combination of both BNP ⩾150 pg/ml and LA enlargement showed a strong association (adjusted OR 4.74, 95% CI 3.47-6.48, p < 0.001) and a good discriminative performance for predicting new AF detection at 3 months (area under the receiver operating characteristic curve 0.74, 95% CI 0.71-0.77, sensitivity 0.70 (95% CI 0.65-0.74), specificity 0.78 (95% CI 0.76-0.80)).

Conclusion: BNP ⩾150 pg/ml within 48 h of IS onset and LA enlargement, especially if combined, may be valuable biomarkers for predicting new AF detection and identifying patients who might benefit the most from extended ECG monitoring.

Background: Timely treatment of ischaemic stroke with intravenous thrombolysis (IVT) and endovascular treatment (EVT) depends on efficient communication within a multiprofessional team. Mobile applications can streamline communication and documentation processes in acute stroke care.

Objective: This study aims to implement a mobile app to facilitate digital documentation and communication in acute stroke care and evaluate its impact on documentation rates and treatment times. Furthermore, a user experience survey was performed to gather information about the app usage in an acute medical process.

Design: The study is designed as an observational post-market clinical follow-up cohort study.

Methods: The mobile app 'Join' was implemented in a tertiary stroke care centre. Feasibility was assessed by monitoring documentation rates and process times, that is, 'door-to-needle time' (DNT) and 'door-to-groin time' (DGT). All patients treated for suspected stroke or transitory ischaemic attack were included in a 6-month period prior to (T1) and a 3-month period after (T2) implementation of the Join app. User experience was evaluated through a standardized survey including technical features.

Results: The interface between the mobile application, hospital information, picture archiving and communication, and quality assurance system as well as various magnetic resonance imaging/computer tomography scanners was implemented for acute stroke care. A total of 504 stroke patients was treated, 334 in T1 and 170 in T2. Of these, 65 received IVT and 87 received endovascular treatment (EVT). DNT (T1 vs T2, 27.5 vs 32 min, p = 0.987) and DGT (T1 vs T2, 50 vs 61.5 min, p = 0.481) were numerically longer during T2. Documentation rates increased threefold for all patients and 1.5 times for those receiving recanalization therapy. The survey revealed that documentation (76%) and case information retrieval (52%) were the most used app features, while other functionalities were less frequently utilized.

Conclusion: Implementing a mobile app facilitated real-time digital documentation accessible to the entire stroke care team. The introduction of the app did not improve treatment times for patients receiving acute recanalizing therapies. We recommend systematic training programmes to promote user acceptance and effective use.

Background: Migraine is a highly prevalent neurological disorder and a leading cause of disability worldwide. Although triptans and non-steroidal anti-inflammatory drugs are widely used, a substantial proportion of patients show inadequate responses. Lasmiditan, a selective 5-HT1_F receptor agonist introduced in Japan in January 2022, represents a novel acute treatment option that lacks vasoconstrictive activity and can be prescribed even in patients with cardiovascular risk. However, little is known about the trend of its long-term real-world use.

Objectives: To characterize 2-year lasmiditan prescription patterns using time-series clustering.

Design: A retrospective observational study using nationwide health insurance claims data in Japan.

Methods: Data were extracted from the REZULT database for patients aged ⩾15 years diagnosed with migraine (ICD-10 code G43) between January 2022 and December 2024. Prescription claims were analyzed in 90-day intervals for up to 24 months after the initial lasmiditan prescription. Time-series clustering was applied to identify subgroups with distinct trajectories of lasmiditan use.

Results: Lasmiditan was prescribed to 21,199 of 167,461 (12.7%) migraine patients (mean age 33.8 ± 10.3 years; 76.6% female). In the first 3 months, 86.2% received 50 mg, 12.8% received 100 mg, and 1.0% received both doses. About half were also prescribed analgesics, 66.7% triptans, and 33.9% prophylactic drugs. Lasmiditan prescriptions were gradually tapered over 2 years, with the most common long-term pattern being combination therapy with analgesics and triptans. Clustering identified three groups: Cluster 1 (massively continuous use), Cluster 2 (gradual tapering), and Cluster 3 (early discontinuation).

Conclusion: This nationwide claims-based study provides the first real-world evidence of long-term lasmiditan prescribing patterns. The identification of three distinct trajectories highlights the heterogeneity of clinical practice. It underscores the need for further research on lasmiditan's optimal use, particularly regarding combination therapy and potential medication overuse.

Background: Neuromyelitis optica spectrum disorder (NMOSD) may be triggered by environmental risk factors.

Objectives: We aimed to explore and integrate the recent research advances in this field. Here we describe relevant studies and summarize current knowledge on non-genetic factors that influence the onset of the disease.

Design: Systematic review.

Methods: We performed a systematic review up to May 21, 2024, following preferred reporting items for systematic reviews and meta-analyses guidelines. Two independent reviewers evaluated the quality of the included studies using the Joanna Briggs Institute checklist for risk of bias assessment.

Data sources: MEDLINE, EMBASE, Scopus, and Web of Science databases.

Results: A total of 15,869 articles were evaluated. Of those 50 studies met the eligibility criteria. A total of 21,410 NMOSD patients were included in the studies; 17,080 patients were females. Totally, 14 risk factors, including vitamin D deficiency, vaccination, virus infections, lifestyle, and dietary factors, were assessed. A total of 37% of the included articles were conducted in East Asia, mainly focusing on the effects of infection and vitamin D deficiency. These studies suggested vitamin D deficiency as a possible NMOSD risk factor. A total of 25% of the studies included Caucasian populations from Western countries. They showed that smoking decreased the odds of NMOSD, in contrast to observations from Eastern studies. Few cases reported NMOSD onset after COVID-19 vaccination. Antibodies against Epstein-Barr virus, Mycobacterium paratuberculosis, and Helicobacter pylori were observed to be more frequently positive in the serum of NMOSD patients. Lower protein and fat and higher carbohydrate intakes were correlated with NMOSD development.

Conclusion: Vitamin D deficiency, cigarette smoking, Mycobacterium avium subspecies paratuberculosis infection, and diet were reported as environmental risk factors for NMOSD. The difference in the onset of NMOSD between Asian and Caucasian populations could be affected by smoking and vitamin D deficiency. Knowledge of modifiable risk factors for NMOSD may be beneficial in preventing and improving disease outcomes.

Acute ischemic stroke (AIS) is a leading cause of long-term disability and mortality worldwide, necessitating the rapid implementation of time-sensitive reperfusion therapies to improve outcomes. The "drip and ship" (DS) model, in which intravenous thrombolysis (IVT) is initiated at a primary stroke center (PSC) followed by transfer for endovascular thrombectomy (EVT) at a comprehensive stroke center, is widely adopted, particularly in regions with limited immediate EVT access. This narrative review synthesizes evidence from randomized-controlled clinical trials, large-scale observational registries, meta-analyses, and expert-consensus statements to comprehensively analyze the DS model in AIS management, compare it with the mothership (MS) paradigm, and evaluate current evidence regarding workflow optimization, pharmacologic strategies, and system-level innovations. Evidence comparing DS and MS models highlights the complexity of balancing early IVT with minimizing delays to EVT, with regional factors influencing the optimal approach. Reducing door-in-door-out times is critical within DS pathways, as prolonged interhospital transfer is associated with worse outcomes, emphasizing the need for streamlined protocols, prehospital notification, and telemedicine integration. Bridging therapy with IVT, particularly using tenecteplase, is associated with improved rates of early recanalization, supporting its continued use within DS workflows. Emerging adjunctive therapies offer potential for enhancing arterial recanalization and microcirculatory reperfusion without delaying transfer. The "drive-the-doctor" paradigm, involving the transfer of neurointerventionalists to PSCs, may further reduce onset-to-reperfusion times in geographically challenging settings. Mobile stroke units, equipped with CT imaging and telemedicine capabilities, represent an additional strategy to initiate IVT in the field while expediting triage decisions for EVT. Collectively, these advancements support the continued refinement of the DS model, emphasizing the need for structured system-level improvements to optimize timely reperfusion and functional recovery in AIS patients. Continued research is necessary to further define optimal strategies within the DS framework to ensure equitable and effective stroke care across diverse healthcare environments.

Migraine with brainstem aura (MBA) constitutes a rare subtype of migraine, characterized by aura symptoms including vertigo, dysarthria, diplopia, tinnitus, ataxia, and impaired consciousness. Patients with MBA have been reported to exhibit abnormal electroencephalograms (EEGs) featuring diffuse slow-wave activity and bilateral slowing of the posterior head activity. Notably, there have been no documented reports of abnormal discharges specifically localized in the anterior head. The presence of abnormal EEG discharges in MBA patients who experience loss of consciousness may lead to potential misdiagnosis, especially as epilepsy, in the early stages. This study describes three patients who were ultimately diagnosed with MBA, offering a retrospective analysis of their clinical features, electroencephalographic manifestations, and diagnostic procedures. In the three cases described, all patients were female, aged 16-21, and had been admitted to the hospital due to recurrent loss of consciousness. They exhibited a consistent EEG pattern, characterized by paroxysmal moderate-to-high amplitude theta activity in the anterior head, interspersed with spikes and sharp waves. Laboratory tests and imaging studies yielded unremarkable results. They all received a diagnosis of epilepsy and were treated with antiseizure medication, which proved ineffective. After evaluation by an epilepsy specialist, they received a final diagnosis of MBA. Following flunarizine administration, all three patients demonstrated improvement, with no subsequent occurrences of loss of consciousness during the follow-up period. This study describes the pattern of abnormal discharges that may be observed in the interictal EEGs of these MBA patients, which is characterized by a predominantly anterior head pattern. Recognizing this specific condition constitutes a crucial element in the differential diagnosis of epilepsy, with the aim of preventing misdiagnosis. Concurrently, we investigate their pathophysiological origins.