Neurology and Therapy最新文献

Introduction: Adrenocorticotropic hormone (ACTH) is a first-line drug and standard therapy in infantile epileptic spasm syndrome (IESS) with different response rates. The mechanism of ACTH for treatment of IESS remains incompletely understood. This study aimed to evaluate short-term outcomes and immunologic mechanisms of ACTH in treating pediatric patients with IESS.

Methods: A multicenter prospective trial of pediatric patients with IESS treated with ACTH over 2 weeks was performed. Short-term responders were defined as those with resolution of epileptic spasms and hypsarrhythmia (if present) at day 14 without epileptic spasm recurrence over 30 days after ACTH therapy, while non-responders included those with persistent spasms or hypsarrhythmia after treatment, or recurrence within 30 days. The risk factors for short-term efficacy were analyzed. The receiver operating characteristic (ROC) curve analysis was adopted to reveal the optimal critical value of peripheral blood lymphocyte subpopulations before ACTH treatment.

Results: Among 151 included pediatric patients, 44 (29.1%) were short-term responders. The presence of hypsarrhythmia on pre-therapy electroencephalogram (EEG) was a risk factor for the short-term efficacy (p = 0.029). A total of 81 patients accepted lymphocyte subpopulation investigation. The short-term responder group had a lower percentage of CD3⁺CD8⁺ T cells (p = 0.080) and a higher CD3⁺CD4⁺/CD3⁺CD8⁺ ratio (p = 0.077) compared to the non-responder group, but the differences were not statistically significant. ROC analysis yielded area under the curve (AUC) values of 0.599 for CD3⁺CD8⁺ T cell percentage and 0.600 for the CD3⁺CD4⁺/CD3⁺CD8⁺ratio. Patients with a CD3⁺CD8⁺ T cell percentage below 19.495% (p = 0.04) and a CD3⁺CD4⁺/CD3⁺CD8⁺ above 2.585 (p = 0.013) had a significantly higher short-term responder rate to ACTH therapy.

Conclusion: About 30% children with IESS were short-term responders to ACTH therapy. The presence of hypsarrhythmia on the pre-therapy EEG was a risk factor for short-term efficacy of ACTH administration. The CD3⁺CD8⁺ T cell percentage and CD3⁺CD4⁺/CD3⁺CD8⁺ ratio may exhibit a predictive capacity.

Stroke remains a leading cause of global disability, perpetuated by maladaptive neuroinflammation that drives secondary injury and impairs recovery. An early reparative (M2) state rapidly transitions into a dominant destructive (M1) phenotype within days, worsening tissue damage through the release of cytokines [tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6)], blood-brain barrier disruption, and amplified peripheral immune cell infiltration. Emerging pharmacological interventions, such as the free radical scavenger edaravone, the neurotrophic factor cerebrolysin, and the excitotoxicity modulator citicoline, demonstrate promising neuroprotective potential when strategically timed. Additionally, novel non-pharmacological approaches, including repetitive transcranial magnetic stimulation, stem cell therapy, and nanoparticle-based drug delivery, offer innovative pathways for targeting neuroinflammation. However, translational challenges persist, including narrow therapeutic windows, biomarker heterogeneity, and preclinical-to-clinical gaps. Future progress necessitates precision medicine paradigms integrating spatiotemporal drug delivery, biomarker-guided intervention timing, and synergistic combinatorial regimens targeting acute injury and chronic repair phases. By bridging mechanistic insights with clinical applications, this review delineates neuroinflammatory modulation as a pivotal frontier for redefining stroke recovery while outlining essential research trajectories to overcome existing barriers. Systematic search of electronic databases including PubMed, Web of Science, Embase, and Cochrane (1996-2025) was performed, with eligible studies assessed using PRISMA guidelines. Findings on neuroinflammation, mechanism, or interventions in ischemic stroke were narratively synthesized through thematic analysis. This review summarizes current insights into post-stroke neuroinflammatory mechanisms, with a focus on the dual role of microglial polarization.

This Summary of Research summarizes a previously published original article, "Fertility Outcomes in Risdiplam-Treated Male Patients with Spinal Muscular Atrophy: A Multicenter Case Series." Risdiplam (EVRYSDI^®) is a medication approved for the treatment of spinal muscular atrophy (SMA), a genetic disease that causes muscle weakness. SMA has been associated with an increased likelihood of decreased fertility compared with the general population. Studies carried out in animals have shown that risdiplam and medications similar to risdiplam disrupt the process by which sperm cells are made. This prompted researchers to question if risdiplam may affect male fertility in humans. This study presented fertility outcomes from three male adults with SMA who conceived with their partners while receiving risdiplam. These cases indicated that there was sufficient sperm production while on risdiplam to result in pregnancy. Two of the pregnancies resulted in healthy, full-term babies who were developing as expected, and one pregnancy was ended voluntarily. Further research is needed to fully understand the effect of risdiplam on male fertility in the broader SMA population. Findings from this research are relevant to male individuals with SMA, their families, caregivers, patient advocates, and healthcare professionals involved in the diagnosis and treatment of SMA.

Synovial cysts originating from the hip joint are rarely symptomatic and are mostly found incidentally by imaging. When the cyst intrudes into the surrounding structures, local pain and swelling, arterial/venous compression, and rarely neurologic symptoms related to disturbance of femoral nerve function can be observed. We report a case of a 78-year-old man who was admitted because of recurrent falls at home over the last weeks. He had been noticing weakness in the right leg, and clinical and neurophysiologic examinations corroborated femoral nerve palsy. A pelvic computed tomography scan depicted a 5-cm-diameter cystic lesion within the right iliopsoas muscle in close contact with the femoral nerve. An ultrasound-guided needle aspiration with evacuation of 5 ml of clear fluid led to a nearly complete resolution of the palsy. We review the available literature on this subject and discuss further differential diagnoses of isolated femoral neuropathy and treatment options for hip joint cysts. Many conditions are associated with falls in older adults. Non-palpable cystic lesions of the hip joint must be considered when clinical examination reveals symptoms of femoral neuropathy. Treatments for symptomatic cysts range from rest, nonsteroidal anti-inflammatory drug administration, and needle aspiration to surgical excision.

Introduction: This analysis used pharmacokinetic (PK) modeling to characterize dosing conversions and switching strategies from R064766, a once-every-2-weeks, intramuscular long-acting injectable antipsychotic (LAI) formulation of risperidone microspheres, and RBP-7000, a subcutaneous (sc) LAI formulation of risperidone administered in the abdomen once monthly (q1m), to TV-46000, a q1m or once-every-2-months (q2m) sc LAI formulation of risperidone.

Methods: Total active moiety (TAM; risperidone + 9-OH risperidone) concentration-time profiles were simulated on the basis of published population PK models with virtual populations of 5000 patients. Simulations were performed to predict TAM exposures when switching to TV-46000 q1m and q2m 2-6 weeks after the last steady-state R064766 injection and 4 weeks after the last dose of RBP-7000.

Results: Comparable doses of oral risperidone, TV-46000, R064766, and RBP-7000 were identified. Initiating TV-46000 4-6 weeks after the last dose of R064766 resulted in similar trends for maximal (C_max) and minimal (C_min) plasma concentration ratios after the first injection for all TV-46000 doses and durations (q1m, q2m) compared with R064766 at steady state. Initiating TV-46000 q1m 4 weeks after the last dose of RBP-7000 resulted in slightly higher, but generally comparable, average plasma concentrations, C_max, and C_min at first dose and at steady state for TV-46000 compared with RBP-7000; C_min of TV-46000 q2m and RBP-7000 were also comparable. Similar trends in plasma concentrations were observed for both back-of-the-upper-arm and abdominal administration when switching from R064766 and RBP-7000 to TV-46000.

Conclusion: These simulations revealed switching to TV-46000 4-6 weeks after the last dose of R064766 and 4 weeks after the last dose of RBP-7000 provided generally comparable PK exposures at first dose and steady state of TV-46000. Clinician discretion will determine which switching strategy is most appropriate in context based on factors such as patient preference, scheduling convenience, and concerns about tolerability.

Introduction: A large-scale post-marketing surveillance (PMS) study is ongoing to evaluate the safety and effectiveness of satralizumab over 6 years in Japanese patients with neuromyelitis optica spectrum disorder (NMOSD) in real-world settings. We present the results of a 30-month interim analysis of the study.

Methods: This PMS is being conducted across 234 sites in Japan. In this 30-month interim analysis, the end of the observation period was defined as either the date of data lock for the 30-month case report form for all patients or the last observation date for patients with satralizumab discontinuation. Primary outcomes include proportion of patients experiencing adverse drug reactions (ADRs), event rate, and oral glucocorticoid use. Secondary outcomes include time to relapse and relapse rate.

Results: Of 571 patients included (mean age: 52.4 years), 91.76% were female. At baseline, 85.98% of patients received oral glucocorticoids. ADRs were reported in 28.72% of patients (event rate: 27.69 events/100 person-years), with infections being most common (11.73%; 8.97 events/100 person-years). Univariate analysis showed that at 30 months, serious infections occurred in 6.83% of patients (5.00 events/100 person-years vs 8.13 events/100 person-years during 0-6 months) and were more frequent in patients aged ≥ 75 years, with diagnosis-to-treatment initiation duration ≥ 10 years, ≥ 3 relapses within 2 years, and Expanded Disability Status Scale score ≥ 6. Mean glucocorticoid dose decreased from 12.27 mg/day (baseline) to 3.48 mg/day (30 months). Kaplan-Meier cumulative relapse-free rate was 85.86% at 30 months. The annualized relapse rate was 0.08/person-year. Overall, 9.63% and 3.50% of patients discontinued treatment because of adverse events and relapses, respectively.

Conclusion: Serious infections were more common during the satralizumab treatment period, occurring most frequently within the first 6 months, highlighting the need for continuous monitoring of infections throughout satralizumab treatment. Satralizumab was found to be safe, without new safety concerns over 30 months. A reduction in concomitant immunosuppressive therapy usage was observed. The study demonstrated the effectiveness of satralizumab in preventing relapses in Japanese patients with NMOSD.

Trial registration: UMIN Clinical Trials Registry, UMIN000041047.

Introduction: Cognitive impairment (CI) spans a spectrum from mild CI to severe dementia, with Alzheimer's disease (AD) the most prevalent cause of CI and dementia. Although dementia burden and prevalence in Arab countries reflect general global trends, the United Arab Emirates (UAE) differs from Western countries both culturally and regarding management resources. Further guidance is therefore needed for the diagnosis and management of CI in the UAE.

Methods: A task force of eight neurologists and two non-voting collaborators with special dementia expertise was convened to develop evidence-based position statements/recommendations to guide the diagnosis and management of AD, including the use of amyloid-targeting therapies (ATTs), in the UAE clinical setting. A modified Delphi survey method was chosen to obtain a consensus, ensuring that drafted expert statements reflected diverse perspectives and experiences. Discordance was predefined as > 25% of panelists rating an expert statement as ≤ 3 on the Likert scale. Consensus was predefined as a median rating ≥ 7 without discordance. Expert statements achieving consensus were adopted.

Results: A seven-step framework for diagnosing and managing CI in the UAE was developed, with consensus achieved on all statements. Recommendations largely aligned with international guidelines on AD dementia management and treatment, combined with UAE-specific guidance. The framework spans the full patient journey from initial symptoms to diagnosis (including biomarker use), initial treatment (including ATTs where appropriate), and subsequent monitoring and management as the disease progresses.

Conclusions: Management of CI and dementia in UAE requires consideration of international guidelines in the context of regional and local cultural sensitivities and healthcare resources. A holistic approach is recommended, combining appropriate pharmacological treatment with lifestyle interventions, education, and support for patients and care partners. Patients require ongoing monitoring to ensure the approach is tailored to the disease stage and provides optimal quality of life and reduced burden for patients and care partners.

Neurodegenerative diseases are among the most prevalent and debilitating disorders in aging populations. Despite growing insights into their complex pathophysiology, effective disease-modifying treatments remain limited. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, primarily used in type 2 diabetes mellitus, have recently gained attention for their potential neuroprotective effects. This narrative review aims to summarize the current preclinical and clinical evidence on the impact of SGLT-2 inhibitors on neurodegenerative diseases, exploring their mechanisms of action, therapeutic potential, and limitations. The authors reviewed experimental studies, animal models, clinical trials, and observational data focusing on the potential links between SGLT-2 inhibitors and neurodegeneration. We further analyzed proposed mechanisms-including metabolic, inflammatory, and vascular factors-in the context of their potential contribution to, or consequence of, neurodegenerative processes, emphasizing their interdependence rather than treating neurodegeneration as an isolated phenomenon. Preclinical studies consistently show that SGLT-2 inhibitors reduce neuroinflammation, improve mitochondrial function, enhance insulin sensitivity in the brain, and may mitigate amyloid and tau pathology. Observational clinical data suggest a lower incidence of dementia in patients treated with SGLT-2 inhibitors. However, cognitive outcomes have not been directly assessed in major randomized trials to date. SGLT-2 inhibitors hold promise as modulators of neurodegenerative processes, but robust clinical trials with cognitive endpoints are needed to confirm their therapeutic relevance. Their potential to bridge metabolic and neurodegenerative pathways highlights a novel avenue for future research and therapeutic development.

Introduction: Generalised myasthenia gravis (gMG) is a rare autoimmune disorder presenting as variable skeletal muscle weakness and fatigue. Comorbidities are common and symptoms are unpredictable and fluctuating. Many patients rely on immunosuppressive treatments including corticosteroids in their disease management, despite adverse events (AEs) associated with extended or high-dose use. We aimed to investigate clinical characteristics, treatment patterns, and disease burden of patients diagnosed with gMG across the Asia-Pacific region.

Methods: Data were drawn from the Adelphi Real World gMG Disease Specific Programme™, a cross-sectional survey of neurologists and their patients with gMG in Australia, China, Japan, South Korea, Malaysia, and Taiwan, from July 2023 to January 2024. Neurologists reported clinical characteristics from diagnosis, current maintenance treatment initiation, and at survey completion.

Results: Neurologists (n = 173) reported data on 407 patients with gMG. At the time of survey, mean (standard deviation) patient age was 51.5 (15.3) years and 58.2% were female. Also at survey, 77.6%, 20.1%, and 2.2% of patients had a Myasthenia Gravis Foundation of America class of II, III, or IV, respectively. Since diagnosis, myasthenic crises (22.5%) or exacerbations (37.2%) were reported for most patients (52.7%). Acetylcholinesterase inhibitors (82.8%) and corticosteroids (69.5%) were most commonly prescribed gMG treatments at survey completion, and 65.1% of patients were not in pharmacological remission. AEs were experienced by 71.0% of those prescribed corticosteroids. Joint effects of corticosteroid dose and duration on the increased number of comorbidities and AEs was significant (p = 0.0319).

Conclusion: Across the Asia-Pacific, most patients did not achieve pharmacological remission despite prescribed treatments, and experienced treatment-related AEs, indicating significant unmet clinical needs. It is suggested that corticosteroid overreliance in maintenance treatment could be associated with increases in comorbidities and AEs. Further research is needed to understand how novel treatments could impact clinical outcomes and reduce corticosteroid reliance for patients with gMG in the Asia-Pacific.

Introduction: While double-filtration plasmapheresis (DFPP) and intravenously administered methylprednisolone (IVMP) are both established treatments for acute attacks of neuromyelitis optica spectrum disorder (NMOSD), their comparative efficacy and safety profiles remain a critical area of investigation. This study aimed to evaluate the clinical outcomes and adverse events of DFPP versus IVMP in patients with NMOSD, with a focus on disability improvement and treatment tolerability.

Methods: A prospective single-center cohort study was performed with 146 patients with NMOSD, who were treated with DFPP, IVMP, and combination therapy (DFPP + IVMP). Primary efficacy was measured by changes in Expanded Disability Status Scale (EDSS) scores (ΔEDSS). Secondary outcomes included Modified Rankin Scale (mRS) scores. Safety profiles, including liver enzyme elevation and infection rates, were monitored.

Results: The DFPP group (n = 81) demonstrated a significant clinical response, with a median EDSS improvement of 0.5 (IQR 0.0-1.0) points. The response rate (defined as ΔEDSS > 0) was 66.7%, with 33.3% (27/81), 18.5% (15/81), and 14.8% (12/81) of patients achieving improvements of 0.5, 1.0, and ≥ 1.5 points, respectively. This was accompanied by a marked reduction in serum immunoglobulins (IgG: 11.87 ± 4.39 to 3.13 ± 1.76 g/L, p < 0.001). The DFPP group and IVMP monotherapy group showed comparable efficacy, with 66.7% (54/81) and 69.2% (45/65) of patients achieving EDSS improvement, respectively (OR 0.89, 95% CI 0.45-1.77, p = 0.742). The magnitude of EDSS improvement was identical between groups (median ΔEDSS 0.5 points). Combination therapy demonstrated particular utility in severe cases (median baseline EDSS 5.0 [IQR 3.5-6.5]). Adverse events were fewer with DFPP than with IVMP (19.8% vs. 33.8%, p = 0.059).

Conclusion: DFPP exhibited comparable effectiveness to IVMP in improving disability during NMOSD acute attacks, with a trend towards a more favorable safety profile. The combination of DFPP and IVMP may benefit severe cases. These findings support DFPP as a viable therapeutic option, particularly for patients with high baseline disability or steroid-refractory disease.