Neurology and Therapy最新文献

Introduction: Embolic stroke is connected to a higher risk of hemorrhagic transformation (HT), functional disability, and mortality. There is a gap of knowledge regarding the predictors of long-term post-alteplase functional outcomes, especially in patients with atrial fibrillation (AF), which limits delivering adequate care and support to stroke survivors. We aimed to assess the predictors of long-term post-thrombolysis unfavorable functional outcomes in patients with atrial fibrillation who presented with first-ever embolic stroke in the Middle East and North Africa (MENA).

Methods: Our prospective cohort study was conducted between May 2021 and May 2025 and included patients with AF who presented with first-ever embolic stroke and received thrombolytic therapy, and who were recruited from Kafr Elsheikh University Hospital, Kafr Elsheikh General Hospital, Al-Sahel Teaching Hospital, NMC Royal Hospital, and Al-Obour Hospital in the period from May 2021 to May 2023. Our longitudinal study included two groups; the unfavorable outcomes group, and the favorable outcomes group.

Results: A total of 580 patients completed the 2-year follow-up period. National institute of health stroke scale (NIHSS) at the time of admission [odds ratio (OR), 2.06; 95% CI, 1.86-4.39; P = 0.03], sustained atrial fibrillation (OR, 1.98; 95% CI, 1.42-3.80; P = 0.03), heart failure (OR, 1.79; 95% CI, 1.23-2.96; P = 0.03), HAS-BLED score (OR, 1.64; 95% CI, 1.41-3.65; P = 0.03), CHA₂DS₂VASc score (OR, 1.72; 95% CI, 1.72-3.53; P = 0.04), post-thrombolysis intracranial hemorrhage (OR, 2.89; 95% CI, 1.74-3.63; P = 0.02), and recurrent symptomatic stroke (OR, 1.98; 95% CI, 1.22-3.73; P = 0.04) were predictors of long-term post-thrombolysis unfavorable outcomes.

Conclusion: Higher baseline NIHSS, heart failure, post-thrombolysis intracranial haemorrhage, and recurrent symptomatic stroke were independent predictors of long-term post-thrombolysis unfavorable functional outcome in embolic stroke patients. Novelly, higher HAS-BLED and CHA2DS2-VASc scores were independent predictors of long-term post-thrombolysis unfavorable functional outcome in Arabian patients. Moreover, sustained AF was an independent predictor of long-term post-thrombolysis unfavorable functional outcome.

Introduction: Ofatumumab (OFA) is a highly effective therapeutic option for multiple sclerosis (MS), but real-world data on its efficacy and safety remain limited. We evaluated the real-world efficacy and safety of OFA in patients with MS and explored the predictive value of frailty.

Methods: We retrospectively collected clinical and MRI data from 12 MS centers in Central Italy, including patients who initiated OFA between April 2022 and January 2024. We assessed annualized relapse rate (ARR), clinical relapses, radiological activity, and safety. Frailty, defined as increased vulnerability due to age-related health deficits, was measured using a frailty index (FI). The study was approved by the local Ethics Committee (No. 6357).

Results: A total of 242 patients with MS were included (66.8% female and 33.2% male; mean age: 38.9 ± 10.3 years; disease duration: 7.7 ± 7.6 years). Of these, 95 (39.2%) were treatment-naïve, and 147 (60.8%) had switched from another therapy, mostly a first switch. The mean follow-up was 15.4 ± 5.4 months; all patients completed 12-month follow-up, and 103 completed 24 months. ARR dropped from 0.9 to 0.02 (p < 0.001). Only 4 patients (1.6%) had a clinical relapse, all within 6 months (mean time: 3.0 ± 1.8 months). Expanded Disability Status Scale (EDSS) scores remained stable (p > 0.05). MRI activity occurred in 10 patients (4.1%) at 6 months and 3 (1.2%) at 12 months; none at 24 months. Adverse events included flu-like symptoms (34.3%), injection site reactions (8.2%), and infections (18.5%). Among 239 patients assessed for frailty (mean FI: 0.06 ± 0.08), 187 were relatively fit (FI ≤ 0.10), 30 least fit, and 22 frail. FI predicted 24-month confirmed disability progression (p = 0.0068), with significant variation by frailty level (p = 0.0009).

Conclusion: This real-world study suggests that OFA is effective and safe for MS, offering rapid disease control. Lower frailty levels suggest preferential use in patients with lower baseline disability. Further large-scale, long-term studies are needed.

Introduction: Generalized myasthenia gravis (gMG) is a chronic autoimmune neuromuscular disorder for which treatment decision-making is increasingly complex due to the emergence of biologic targeted therapies. This study aimed to evaluate neurologists' treatment preferences in acetylcholine receptor seropositive gMG using conjoint analysis to simulate real-world clinical decision-making.

Methods: We conducted a cross-sectional, web-based study among neurologists involved in the management of gMG in collaboration with the Spanish Society of Neurology. Participants were presented with eight hypothetical treatment scenarios comprising five key attributes: intensity of improvement, onset of action, duration of effect, adverse events, and route/frequency of administration. Utility values and importance of each attribute were estimated using ordinary least squares regression. Demographic, professional, and behavioral characteristics were assessed to explore variability in preference patterns.

Results: A total of 149 neurologists participated in the study. The mean age was 39.0 (SD 9.4) years, and 54.4% were male. Participants had a mean of 9.9 years (8.4) of experience treating patients with MG. The most valued treatment attribute was intensity of improvement (mean relative importance: 38.6%), followed by onset of action (21.5%) and duration of effect (17.4%). At the individual level, route and frequency of administration accounted for up to 21.9% of decision weight in some participants. Preferences were consistent across neuromuscular specialists and general neurologists but differed based on empathy and conscientiousness. Model fit was robust (Pearson's R = 1.000, p < 0.001).

Conclusions: Neurologists treating gMG placed the highest value on rapid and clinically meaningful symptom improvement, consistent with the therapeutic goals of emerging targeted therapies. However, substantial heterogeneity in preferences, especially regarding administration burden, emphasizes the need for individualized approaches and shared decision-making.

Introduction: Guillain-Barré syndrome (GBS) is an acute immune-mediated disorder of the peripheral nervous system, marked by rapid onset of neurological symptoms. Despite progress in understanding the etiology and improving clinical management, no validated biomarkers are currently available to predict disease severity or treatment response during the acute phase. This meta-analysis aims to evaluate the role of serum neurofilament light chain (NfL) as a biomarker of acute disease activity and prognostic outcomes in GBS.

Methods: A systematic review and meta-analysis was conducted using PubMed, Scopus, and Cochrane Library databases to identify studies assessing NfL levels in patients with GBS. In addition, we included data from our own cohort of patients with GBS-whose NfL levels were measured at disease onset-and from healthy controls. The primary outcome was the difference in NfL levels-both in serum and cerebrospinal fluid (CSF)-between patients with GBS and controls. Secondary outcomes included the correlations between acute-phase NfL levels, clinical severity at admission as measured by the Guillain-Barré Disability Scale (GBDS) or the Hughes Functional Scale (HFS), and long-term outcomes such as the inability to walk or run 1 year after disease onset.

Results: In this meta-analysis of nine studies, which also included data from our cohort, serum NfL levels were significantly higher in patients with GBS compared with controls (mean difference 143.17 pg/mL, 95% CI 67.7-218.6; p < 0.01; I² = 83%). In contrast, the difference in CSF NfL levels only approached statistical significance (mean difference 2091.1 pg/mL, 95% CI 171.2-4353.4; p = 0.07, I² = 92.1%). These findings were corroborated in our cohort, where median serum NfL concentrations were markedly higher in patients with GBS compared to controls (97 pg/mL, IQR 79-194 vs. 15 pg/mL, IQR 13-20; p < 0.05, Wilcoxon rank-sum test). Serum NfL levels were higher in patients with the acute motor axonal neuropathy (AMAN) compared to those with acute inflammatory demyelinating polyneuropathy (AIDP) (MD 531.9 pg/mL, 95% CI 32.8-1031.01; I² = 81.1%; p = 0.04). Moreover, NfL levels positively correlated with disease severity at admission (r = 0.38; p < 0.001) and poor long-term outcomes (OR 3.74, 95% CI 1.05-13.37; p < 0.001).

Conclusion: Serum NfL is a promising biomarker for early diagnosis and prognosis in GBS and may support risk stratification at hospital admission.

Introduction: Dementia with Lewy bodies (DLB), a common cause of dementia, has no FDA-approved therapies, and clinical trials to date have had limited ability to demonstrate efficacy. The lack of validated DLB-specific clinical trial outcomes may hinder these efforts. Here, we test whether the Clinical Dementia Rating (CDR) and other commonly used clinical evaluation tools for Alzheimer's disease (AD) and Parkinson's disease (PD) could potentially be used as outcome measures in future DLB clinical trials.

Methods: A retrospective, cross-sectional chart review of 600 patients (359 AD, 241 DLB) who completed a comprehensive clinical, cognitive, functional, and behavioral evaluation over a 10-year period was carried out. Performance of the CDR, its sum of boxes (CDR-SB), and other AD and PD evaluation measures were assessed for stage-wide performance from mild cognitive impairment (CDR 0.5) to moderate-severe dementia (CDR 2).

Results: The CDR and CDR-SB characterize important differences between AD and DLB across different cross-sectional stages of disease severity, with the greatest differences seen at the CDR 0.5 stage. DLB showed greater deficits in commonly used AD functional and behavioral measures at the CDR 0.5 stage, while more DLB-specific measures showed significant differences from AD across the entire disease spectrum. The patient version of the Quick Dementia Rating System showed greater stage-wide impairment in DLB than AD, supporting its use as a patient-reported outcome. The Montreal Cognitive Assessment showed greater stage-wide impairment in AD than in DLB patients, suggesting lack of sensitivity as an outcome measure for DLB clinical trials.

Conclusion: Improved study design and selection of appropriate outcome measures in DLB clinical trials can facilitate demonstration of efficacy. While the CDR-SB could work on a DLB clinical trial, the field would be most advanced by the development of a DLB-specific global rating instrument.

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder causing significant suffering and mental health problems for patients. Many patients with ALS have a severe psychological reaction to the serious diagnosis when they are first diagnosed. This study aims to investigate the impact of a brief mindfulness intervention on emotions, sleep, and quality of life (QOL) in patients with ALS who have recently been diagnosed.

Methods: This prospective intervention study enrolled patients who had been newly diagnosed with ALS. Participants received cognitive training and audio-led mindfulness exercises involving breathing awareness and body scan sessions for 10 days. The effectiveness of the intervention was evaluated by several scales.

Results: Ninety-one patients (aged 54.15 [10.10] years, 52 male/39 female [57.10%/42.90%]) were finally enrolled in the analysis. The Chinese Version Perceived Stress Scale (CPSS) (t = 2.05, P = 0.04) and Epworth Sleepiness Scale (ESS) (Z = -2.03, P = 0.04) scores significantly decreased, and the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ40) significantly increased (Z = -2.93, P < 0.01) following the brief mindfulness intervention. The Patient Health Questionnaire-9 (PHQ-9) (Z = -2.97, P < 0.01) and the 17-Item Hamilton Rating Scale for Depression (HAMD-17) (Z = -3.43, P < 0.01) were significantly reduced in patients with ALS diagnosed with depression. QOL was significantly improved in other patients with ALS (Z = -2.51, P = 0.01).

Conclusion: Our study indicated that a brief mindfulness intervention could be a potential way to reduce depression and improve daytime sleepiness, while also improving the QOL for newly diagnosed patients with ALS.

Introduction: Sphingosine-1-phosphate receptor (S1PR) modulators are effective therapies for multiple sclerosis (MS) that block lymphocyte egress from secondary lymphoid organs. This migration inhibition carries the risk of reduced infection-control as reported for the non-selective S1PR modulator, fingolimod. CXCL13:CXCR5-associated immune activities play a key role in protective antibody-based immunity but are also linked to inflammation in MS. Utilizing the ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, we aimed to determine whether selective S1PR modulation with ozanimod acts on the CXCL13:CXCR5 axis for modulating MS activity and whether this impacts anti-viral immune responses.

Methods: This 1-year observational study included 20 patients with MS receiving ozanimod and 10 healthy probands. CXCR5⁺ T cells, B cells, serum CXCL13, anti-SARS-CoV-2 serostatus, and SARS-CoV-2-spike protein (ProtS)-reactive T cell responses were measured at 3-month intervals.

Results: CXCR5⁺ T and B cell frequencies and serum CXCL13, but not anti-SARS-CoV-2 responses, declined after ozanimod initiation. Anti-SARS-CoV-2 antibody and ProtS-reactive T cell responses peaked after recall vaccinations and break-through infections. Notably, ProtS-reactive T cell frequencies shifted from CD4⁺ to CD8⁺ T cell responses in patients treated with ozanimod compared to controls.

Conclusion: Selective S1P receptor modulation with ozanimod affects the CXCL13:CXCR5 axis by reducing circulating CXCR5⁺ lymphocytes and serum CXCL13, which may contribute to reduce meningeal inflammation in MS. Moreover, the anti-SARS-CoV-2 immune defense appeared to be preserved during treatment with SARS-CoV-2-reactive CD8⁺ T cells, possibly compensating the lack of CD4⁺ T cell responses. Our immunological data may well apply to other viral infections and underscore the favorable safety and efficacy profile of ozanimod.

Introduction: Despite the availability of effective treatments, some patients with migraine in Japan do not receive appropriate medical management and treatment for migraine, potentially due to the lack of effective patient-doctor communication. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan)] 2nd study described the current state and challenges of patient-doctor communication in migraine treatment in Japan.

Methods: This analysis included adults with migraine who consulted doctors for headaches/migraine and reported details of their first consultation: their experiences with doctors regarding migraine diagnosis and treatments, migraine-related topics, and treatment goals discussed, and challenges in communication.

Results: Among the 6762 included respondents, 55.1% (3729/6762) consulted a general practitioner (GP) first for headaches. Of the 3192 respondents diagnosed with migraine and reported the diagnosing doctor's specialty (as GP, specialist, or non-headache specialist), specialists (64.0%; 2044/3192), followed by GPs (31.4%; 1001/3192), mostly commonly diagnosed migraine. In the first consultation, doctors told 48.0% (3249/6762) of respondents they had migraine. In the past year, 3854 respondents discussed migraine-related topics with doctors; most commonly, the use and effectiveness of prescription drugs, and headache symptoms, severity, and frequency [48.9% (1885/3854) to 67.8% (2612/3854)]. Specialists most commonly discussed migraine-related topics with respondents, but non-headache specialists, i.e., obstetricians and gynecologists, most commonly discussed menstrual-related migraine. A total of 1978 respondents had migraine-related topics they wanted to but could not discuss with doctors in the past year. Among them, 32.9% (651/1978) of respondents did not discuss the topics because the doctor did not ask. Although 96.6% (3724/3854) of respondents had treatment goals in mind, 36.0% (1388/3854) never discussed it with doctors.

Conclusion: Open and considerate patient-doctor communication and appropriate medical judgment are needed for timely and adequate medical management of migraine. Training doctors in effective communication techniques and considering a migraine diagnosis during consultations may be associated with better patient outcomes.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease, affects the optic nerves and spinal cord. Rituximab is often used off-label to treat NMOSD; however, comparator-controlled trial data are limited. Eculizumab is approved for treatment of anti-aquaporin-4 antibody-positive (AQP4-Ab+) NMOSD. Outcomes data for patients who switch from rituximab to eculizumab are limited.

Methods: This retrospective study used claims data from the IQVIA PharMetrics^® Plus database (1/1/2015-3/31/2022). Patients aged ≥ 18 years with NMOSD treated with rituximab were identified and split into two groups: patients with an eculizumab claim after rituximab (switch group, n = 20) and patients without an eculizumab claim (control group, n = 525). Hospitalization rates and duration were assessed 6 months before and 6 months after the switch date (switch group) or reference date (1-year post-rituximab initiation; control group).

Results: The percentage of patients hospitalized in the switch group decreased after transitioning to eculizumab (45.0% vs. 10.0%; p = 0.034) corresponding to a decreased mean number of hospitalizations per patient from 1.1 to 0.1 (p = 0.005). The percentage of patients hospitalized in the control group was similar before and after the reference date (10.1% vs. 9.3%; p = 0.755) corresponding to a mean number of hospitalizations per patient of 0.160 and 0.156 (p = 0.922), respectively. In the switch group, median (interquartile range [IQR]) hospitalization duration decreased from 8.5 (5.0-11.0) days before switching to eculizumab to 2.5 (2.2-2.8) days after switching (p < 0.001). Median (IQR) hospitalization duration in the control group was 4.0 (2.0-9.0) days before and 4.0 (2.0-6.0) days after the reference date.

Conclusion: Although the claims-based analysis and small patient numbers limit generalizability, we observed a reduction in hospitalizations number and length of stay in a cohort of patients with NMOSD who switched from rituximab to eculizumab.

Central post-stroke pain (CPSP) is an intractable neuropathic pain syndrome. Dual-target deep brain stimulation (DBS), which integrates sensory thalamic modulation and endogenous analgesic pathways, has emerged as a potential intervention; however, clinical evidence remains scarce. We report a 54-year-old woman who developed right-sided limb paresthesia progressing to persistent right hemibody pain following a left thalamic hemorrhage. Asymmetric DBS electrodes were implanted in the right periaqueductal gray (R-PAG) and left ventral posterior thalamus (L-VP). Longitudinal assessments utilized standardized scales-including the Visual Analog Scale (VAS), Douleur Neuropathique 4 (DN4) and Hamilton Depression Scale (HAMD). These evaluations demonstrated sustained improvements in pain intensity (VAS: 7 → 1), neuropathic symptoms (DN4: 4 → 1) and depressive symptoms (HAMD: 22 → 8) at the 12-month follow-up. Pain and transient numbness were mitigated by applying cyclic stimulation (5-min on/off intervals). This case highlights the potential of asymmetric dual-target DBS targeting both the PAG and VP to achieve multidimensional analgesia in CPSP and provides insights for optimizing patient selection and treatment strategies, including choices of targets, stimulation parameters and modalities. These findings enhance understanding of neural pathways in chronic pain modulation, specifically the interplay between sensory and emotional processing, and suggest a potential role for asymmetric DBS in treating neuropathic pain.