Neurology and Therapy最新文献

{"title":"Positioning Cenobamate in the Treatment Algorithm of Focal Epilepsy: Seizure Control and Benefits Beyond Seizures.","authors":"Manuel Toledo, Vicente Villanueva, Irene García-Morales, Juan Jesús Rodríguez-Uranga, Mar Carreño, José María Serratosa","doi":"10.1007/s40120-026-01067-y","DOIUrl":"https://doi.org/10.1007/s40120-026-01067-y","url":null,"abstract":"<p><p>This work integrates the opinion on the current use of cenobamate (CNB) of an expert panel structured across seven thematic domains: efficacy, patient profiles, titration and dosing, pharmacokinetic interactions, safety, parallel effects, and therapeutic positioning. According to personal experience and scientific evidence, experts unanimously regarded CNB as likely more efficacious than other newer-generation antiseizure medications (ASMs), particularly based on the long-term sustained seizure-freedom rates, despite the absence of comparative head-to-head studies. Priority candidates are patients with focal epilepsy failing two or more ASMs, including older patients, with a clear inclination toward earlier introduction. Initial response is expected at 100-200 mg/day, although maintenance is typically 200 mg/day or higher, alongside reduction of concomitant ASMs particularly sodium channel blockers and benzodiazepines. The most relevant drug-drug interaction is with clobazam, which may have a synergistic efficacy effect and in parallel increases plasma concentrations of clobazam, thereby inducing adverse events. The most frequent adverse events (somnolence, dizziness, fatigue) are dose-dependent and are reduced by anticipatory reduction of concomitant medication. Beyond seizure reduction, an early intervention with CNB may modify the prognosis of epilepsy, reducing the long-term mortality risk, cognitive impairment, or psychiatric disorders. The panel converged on a priority to position CNB as a third-line treatment in the focal epilepsy treatment algorithm owing to its high efficacy, which will probably lead to modification of the long-term global outcomes of people with epilepsy.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brexpiprazole for Individual Agitation Symptoms in Alzheimer's Dementia: A Caregiver-Centered Post Hoc Analysis.","authors":"Anton P Porsteinsson, Sanjeda R Chumki, Anton M Palma, Zhen Zhang, David Wang, Pedro Such, C Brendan Montano","doi":"10.1007/s40120-026-01037-4","DOIUrl":"https://doi.org/10.1007/s40120-026-01037-4","url":null,"abstract":"<p><strong>Introduction: </strong>People with Alzheimer's dementia commonly experience agitation symptoms, which are distressing to caregivers and can influence long-term care decisions. The aim of this exploratory post hoc analysis was to test the hypothesis that brexpiprazole can improve individual agitation symptoms over 12 and 24 weeks, including symptoms that caregivers find the most distressing.</p><p><strong>Methods: </strong>Data were included from two phase 3, 12-week, randomized (brexpiprazole or placebo), double-blind trials and a phase 3, 12-week, brexpiprazole-treatment extension trial. Participants had Alzheimer's dementia with agitation, and lived at home or in long-term care. The frequency of 29 agitation symptoms over 12 and 24 weeks was assessed using Cohen-Mansfield Agitation Inventory (CMAI) item scores. The focus of this post hoc analysis was the 11 CMAI agitation symptoms that caregivers found the most distressing in a prior survey.</p><p><strong>Results: </strong>Among 610 participants (median age 74 years, 55.5% female, 44.5% male), each of the 11 most-distressing agitation symptoms reduced in frequency from baseline to Week 12, with further improvements to Week 24 (n = 159). Improvements over 12 weeks were numerically greater with brexpiprazole 2 or 3 mg/day (n = 363) compared with placebo (n = 247) on 9 of 11 symptoms: cursing or verbal aggression, spitting, repetitive sentences or questions, hitting, constant unwarranted requests for attention/help, trying to get to a different place, pacing or aimless wandering, grabbing onto people or things, and kicking. Each of the 18 other agitation symptoms (beyond the most distressing) also reduced in frequency. After 24 weeks, 15 of 29 agitation symptoms occurred less than once a week.</p><p><strong>Conclusion: </strong>Brexpiprazole was associated with improvement in a range of agitation symptoms in people with Alzheimer's dementia, including those that are the most distressing to caregivers. These exploratory results suggest that brexpiprazole may improve the specific agitation symptoms that can have the biggest impact on the caregiver experience.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers: NCT01862640, NCT03548584, NCT03594123.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Health Care Resource Utilization, Adherence, and Persistence Following Subcutaneous IgPro20 Initiation Among US Patients with Chronic Inflammatory Demyelinating Polyneuropathy.","authors":"Batyrkhan Kuatov, Shicheng Weng, Alphonse Hubsch, Laurence Undreiner, Aisara Chansakul, Ann Madsen, Elizabeth C Dabrowski","doi":"10.1007/s40120-026-01051-6","DOIUrl":"https://doi.org/10.1007/s40120-026-01051-6","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, inflammatory peripheral nervous system disorder. Intravenous immunoglobulin (IVIG) has been the standard maintenance therapy, but since 2018, Immune Globulin Subcutaneous (Human), 20% liquid (IgPro20), a subcutaneous immunoglobulin (SCIG) therapy, has offered an alternative, demonstrating benefit in maintaining CIDP improvement and remission. This study aimed to evaluate real-world healthcare resource utilization (HCRU), adherence, and persistence following IgPro20 initiation in patients with CIDP, given limited real-world evidence on these SCIG-related outcomes.</p><p><strong>Methods: </strong>This observational, descriptive study used Optum's de-identified Clinformatics^® Data Mart Database (Optum^® CDM) data to examine adults with CIDP initiating IgPro20 (index date). Adult patients with ≥ 2 CIDP diagnosis claims at least 14 days apart and ≥ 6 months of enrollment pre- and post-index between January 1, 2014 and December 31, 2024 were included. Those on other SCIG products were excluded.</p><p><strong>Results: </strong>Patients with CIDP initiating IgPro20 (N = 207) were 53.6% male, with a median age of 60.00 and few comorbidities. Acute care utilization was low at baseline and decreased further following IgPro20 initiation, with inpatient and emergency department visits per patient per year (PPPY) decreasing from 0.52 to 0.42 and from 1.00 to 0.85, respectively. Overall, outpatient (OP) visits increased from 60.62 PPPY pre-initiation to 92.61 PPPY in month 1 post-initiation, driven by visits for CIDP-related home administration, notably for nursing/home-care for self-administration training. OP visits subsequently declined to 67.43 PPPY by month 6 (n = 141). Most patients (69.1%) were highly adherent, and 63.8% remained persistent at 6 months.</p><p><strong>Conclusion: </strong>Patients on IgPro20 administration demonstrated therapy adherence and decreased utilization of resource-intensive settings. While initial increases in outpatient and home care visits likely reflect training for at-home therapy, other outpatient healthcare utilization decreased. High persistence and adherence indicate sustained, uninterrupted therapy.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil to Lymphocyte Ratio and Neurological Outcome in Ischemic Stroke at 4.5 to 24 Hours: A Post Hoc Analysis of TRACE-III Trial.","authors":"Manjun Hao, Yujie Ma, Lihua Wang, Aoming Jin, Zhe Kang Law, Bruce C V Campbell, Lee H Schwamm, Mark W Parsons, Marc Fisher, Yuming Xu, Anding Xu, Zhixin Cao, Liyuan Wang, Shuangzhe Wu, Yongjun Wang, Yunyun Xiong","doi":"10.1007/s40120-026-01060-5","DOIUrl":"https://doi.org/10.1007/s40120-026-01060-5","url":null,"abstract":"<p><strong>Introduction: </strong>Whether neutrophil to lymphocyte ratio (NLR), as a marker of increased inflammatory response, modifies the efficacy and safety of tenecteplase is uncertain in patients 4.5-24 h after stroke onset. We investigated this in the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE-III) trial.</p><p><strong>Methods: </strong>TRACE-III was a phase 3, multicenter, prospective, open-label, randomized, blinded-endpoint trial that enrolled 516 patients from 58 centers in China between January 2022 and November 2023. Patients had anterior large vessel occlusion and evidence of salvageable brain tissue on perfusion imaging, presented 4.5-24 h after symptom onset, and were randomized 1:1 to intravenous tenecteplase (intervention) or standard medical treatment (control). The primary efficacy and safety outcomes were modified Rankin scale score of 0-1 at 90 days and symptomatic intracranial hemorrhage or death, respectively. This post hoc analysis in 513 patients with complete admission NLR data compared outcomes in patients with elevated NLR (> first quartile) and non-elevated NLR (≤ first quartile).</p><p><strong>Results: </strong>In the elevated NLR group (> 3.0), tenecteplase was associated with increased functional independence (61 [30.2%] vs. 36 [19.6%]; adjusted relative rate [aRR] 1.51; 95% confidence interval [CI] 1.05-2.17; P = 0.03) compared to standard medical treatment. This benefit was not observed in the non-elevated NLR group (26 [41.9%] vs. 25 [38.5%]; aRR 1.12; 95% CI 0.73-1.73). Safety outcomes did not differ in either the elevated or non-elevated NLR groups.</p><p><strong>Conclusion: </strong>Baseline NLR may provide a potential signal for differential treatment response to intravenous tenecteplase in patients with acute ischemic stroke, although these exploratory findings require further validation in independent studies.</p><p><strong>Trial registration: </strong>TRACE-III is registered with ClinicalTrials.gov, NCT05141305.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Serum IgG Reduction as a Potential Indicator of Short-Term Clinical Improvement in AChR-Ab-Positive Generalized Myasthenia Gravis: A Post Hoc Analysis of a Phase III Batoclimab Trial.","authors":"Zhijun Li, Qing Ke, Jianying Xi, Yaoxian Yue, Yuzhou Guan, Ruisheng Duan, Qun Xue, Haishan Jiang, Fei Xiao, Huan Yang, Ting Chang, Zhangyu Zou, Haifeng Li, Song Tan, Haibing Xiao, Hongyu Zhou, Hua Zhang, Qiang Meng, Wenyu Li, Wei Li, Junhong Guo, Yali Zhang, Zunbo Li, Jianglong Tu, Jianquan Shi, Wei Li, Chongbo Zhao, Shuai Zhao, Chen Zong, Hui Deng, Bitao Bu","doi":"10.1007/s40120-026-01019-6","DOIUrl":"https://doi.org/10.1007/s40120-026-01019-6","url":null,"abstract":"<p><strong>Introduction: </strong>Generalized myasthenia gravis (gMG) is an autoimmune disorder often associated with anti-acetylcholine receptor antibodies (AChR-Abs). Identifying short-term predictors or indicators of clinical improvement is crucial for optimizing treatment strategies.</p><p><strong>Methods: </strong>This post hoc analysis utilized data from a phase III, multicenter randomized controlled trial enrolling 65 patients with AChR-Ab-positive gMG across 27 centers in China. We evaluated serum immunoglobulin G (IgG) as a potential short-term indicator of clinical improvement in patients treated with batoclimab. Clinical severity was evaluated using the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales. Spearman correlation analyses, mixed-effects models, and multivariate analyses were performed to assess relations between biomarker changes and symptom improvement.</p><p><strong>Results: </strong>Within-patient Spearman correlation showed significant associations between reductions in IgG or AChR-Ab levels and symptom improvement (ΔIgG vs. MG-ADL change: r = 0.372, p < 0.001; ΔIgG vs. QMG change: r = 0.492, p < 0.001). Mixed-effects modeling indicated that an 80% reduction in IgG corresponded to a 59% probability of MG-ADL improvement by ≥ 3 points and a 77% probability of QMG improvement by ≥ 3 points. High baseline body mass index (BMI) was identified as an independent risk factor for slower IgG decline.</p><p><strong>Conclusion: </strong>Batoclimab rapidly reduced IgG and pathogenic AChR-Ab levels, leading to improved clinical outcomes in patients with gMG. The reduction rate in total IgG may serve as a valuable short-term indicator of clinical response in patients with AChR-Ab-positive gMG following neonatal fragment crystallizable receptor antagonist therapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier NCT05039190.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards a Better Definition of Patient-Centered Therapeutic Strategy of Parkinson's Disease: An Opinion Paper.","authors":"Heinz Reichmann, Angelo Antonini, Kallol Ray Chaudhuri, Teodor Danaila, David Devos, Thomas Foltynie, Silvia Jesús Maestre, Wolfgang H Jost, Valtteri Kaasinen, Regina Katzenschlager, Lydia López Manzanares, Javier Pagonabarraga Mora, Patrick Santens, Diego Santos García, Stefano Tamburin, Jürgen Winkler, Olivier Rascol","doi":"10.1007/s40120-026-01055-2","DOIUrl":"https://doi.org/10.1007/s40120-026-01055-2","url":null,"abstract":"<p><p>Recent Parkinson's disease (PD) treatment guidelines remain predominantly drug- and stage-centric and only inconsistently articulate a patient-centered medication strategy. We aimed to identify this gap and propose pragmatic, consensus-based principles for fully individualized, preference-sensitive pharmacological care across the patient journey. Seventeen movement disorder experts from eight European countries convened (March 2026) and generated key clinical questions spanning early to advanced PD. Panelists completed an anonymized questionnaire; semantic AI supported identification of areas of consensus and dissensus, followed by a single-round Delphi-style discussion to refine agreed statements. The panel reached consensus on eight statements across five focus areas: (i) incorporating patient characteristics and contextual factors underrepresented in guidelines (comorbidities, co-medications, behavioral/cognitive risk, non-motor symptom burden, and-when appropriate-genetics); (ii) treating therapy initiation as a longitudinal process with shared decision-making, education, and non-pharmacological foundations; (iii) legitimizing watchful waiting or dose reduction in selected scenarios; (iv) using both motor and non-motor symptoms and lifestyle goals as primary drivers of oral therapy selection; and (v) transparently managing evidence gaps while providing good-practice guidance on reassessment. Examples on how these recommendations can be used to plan a therapy strategy are presented for different patients' personae. In conclusion, a patient-centered medication strategy in PD should be explicit, structured, and revisited over time, aligning therapeutic choices with symptoms, risks, context, and individual goals and preferences. A wide range of treatments must always be available throughout the patient's care pathway to allow for greater individualization of care, particularly regarding treatment sequencing, drug combinations, and dosage thresholds. This requires new forms of validation beyond traditional standardized clinical trials.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Pain Intensity: A Patient-Informed Framework for Documenting Burden in Small Fiber Neuropathy.","authors":"Guy Hochman","doi":"10.1007/s40120-026-01063-2","DOIUrl":"https://doi.org/10.1007/s40120-026-01063-2","url":null,"abstract":"<p><p>Small fiber neuropathy (SFN) is a sensory-autonomic neuropathy of thinly myelinated Aδ and unmyelinated C fibers that can produce neuropathic pain and multisystem autonomic symptoms. Although diagnostic criteria and confirmatory testing have improved recognition, SFN burden may remain underrecognized even after diagnosis. This narrative review identifies two complementary documentation failures. The translation problem arises when symptom labels and intensity ratings do not capture effects on sustainable function, cognitive workload, emotional well-being, and participation. The fragmentation problem arises when specialties assess multisystem symptoms without preserving their temporal pattern, co-occurrence, shared triggers, treatment trade-offs, and recovery costs. Reverse availability bias is proposed as a conceptual mechanism that may intensify both failures: symptoms or mechanisms not represented in clinicians' mental models may be overlooked in consideration and documentation. The review proposes an SFN Burden Integration Framework (SFN-BIF) that separates symptom presence, burden, and causal attribution and combines validated measures with six core documentation fields: temporal pattern, triggers and relievers, co-occurrence, recovery cost, functional consequences, and cognitive-emotional consequences. Longitudinal patient-reported information is integrated with neurological examination, skin biopsy, quantitative sensory testing, autonomic or organ-specific testing, and cognitive or functional assessment when indicated. Better integration may inform diagnosis and referral, treatment selection and trade-offs, rehabilitation and psychological care, disability assessment, phenotyping, and clinical trial outcome selection while preserving diagnostic rigor. The framework remains conceptual and requires prospective evaluation of validity, feasibility, clinical utility, and administrative burden.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wearable Electromyography and Inertial Sensor Phenotypes Across Clinical Subtypes of Parkinson's Disease.","authors":"Ruizi Tu, Li Xue, Xian Liu, Kunpeng Qin, Zihan Wang, Bohan Yang, Can Liu, Yixuan Tao, Min Cai, Anmu Xie","doi":"10.1007/s40120-026-01054-3","DOIUrl":"https://doi.org/10.1007/s40120-026-01054-3","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is clinically heterogeneous, yet whether the mild motor-predominant, intermediate, and diffuse malignant (MMP/IM/DM) subtypes show objective neuromuscular and kinematic phenotypic differences remains unclear.</p><p><strong>Methods: </strong>We studied 120 patients with PD (55 men and 65 women) in the medication ON state. Subtypes were assigned using motor, cognitive, rapid eye movement sleep behavior disorder, and autonomic domains. Synchronized surface electromyography and inertial recordings were obtained from the more affected upper limb during three tremor and three movement tasks. Digital motor features were compared across subtypes using covariate-adjusted linear mixed-effects models with false discovery rate (FDR) correction. Subject-level associations with DM membership were examined using Firth penalized logistic regression with LASSO-based feature selection.</p><p><strong>Results: </strong>Of 120 patients, 54 were classified as MMP, 46 as IM, and 20 as DM. Clinical burden showed a graded pattern, with the greatest motor and non-motor impairment in DM. Among all digital motor domains, only amplitude/speed remained significant after FDR correction (p = 0.006). Greater amplitude/speed impairment was associated with DM versus non-DM membership in the Firth logistic regression (OR 2.902, 95% CI 1.201-10.186) and in the subsequent LASSO-selected Firth model (OR 4.444, 95% CI 1.879-13.986). Lower tremor amplitude also independently distinguished DM from non-DM (OR 0.019, 95% CI < 0.001-0.327).</p><p><strong>Conclusions: </strong>MMP/IM/DM subtypes exhibit measurable EMG/IMU phenotypic differences beyond conventional clinical evaluation. The amplitude/speed domain may represent a candidate digital marker for the DM phenotype, outperforming tremor and other motor domains. Longitudinal and multimodal studies are warranted to validate its prognostic and mechanistic significance.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the Use of Anti-CD20 Agents in Multiple Sclerosis and Other Autoimmune Central Nervous System Disorders: A Narrative Review.","authors":"Diana Ferraro, Gianmarco Abbadessa, Federica Azzolini, Assunta Bianco, Sara Carta, Alessandro Dinoto, Gabriele Di Sante, Giorgia Teresa Maniscalco, Sara Mariotto, Gabriela Constantin, Massimiliano Di Filippo, Raffaele Iorio, Roberta Magliozzi, Rosella Mechelli, Claudio Procaccini, Elisabetta Signoriello, Diego Centonze","doi":"10.1007/s40120-026-01048-1","DOIUrl":"https://doi.org/10.1007/s40120-026-01048-1","url":null,"abstract":"<p><p>Anti-CD20 monoclonal antibodies have become central therapies for multiple sclerosis (MS) and other autoimmune disorders of the central nervous system, including neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and autoimmune encephalitis. These agents robustly suppress inflammatory disease activity through prolonged B-cell depletion; however, cumulative exposure is associated with increased infection risk, hypogammaglobulinemia, and impaired vaccine-induced humoral responses. In recent years, extended interval dosing (EID) and dose-reduction strategies have emerged as potential approaches to mitigate long-term safety concerns while preserving therapeutic efficacy. This review, a joint effort of the Steering Committees of the Italian Neuroimmunology Association and of the Neuroimmunology Study Group of the Italian Society of Neurology, summarizes current evidence on long-term anti-CD20 treatment optimization across autoimmune central nervous system (CNS) disorders, with particular focus on cumulative exposure, extended-interval dosing, dose reduction, B-cell-guided retreatment, treatment discontinuation, and safety monitoring. This review does not provide formal consensus recommendations but highlights disease-specific considerations that may help clinicians balance sustained disease control against cumulative treatment-related risks. Observational studies in MS suggest that EID of ocrelizumab and rituximab may maintain short-term clinical and radiological disease control in selected stable patients while potentially reducing immunoglobulin decline and improving vaccine responsiveness. However, the available evidence remains heterogeneous and largely based on retrospective real-world cohorts. In NMOSD, rituximab remains widely used despite the availability of newer targeted therapies, and individualized reinfusion strategies based on B-cell monitoring may help balance efficacy and safety. By contrast, anti-CD20 efficacy in MOGAD appears less consistent, whereas in autoimmune encephalitis rituximab is particularly effective in antibody-mediated disease associated with neuronal surface antigens. Overall, strategies to reduce cumulative anti-CD20 exposure represent a promising direction for long-term treatment optimization, although prospective randomized studies are still needed to define the safest and most effective dosing approaches.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraneoplastic Intracellular Neuropathies: A Narrative Review.","authors":"Giovanni Siconolfi, Benjamin Mathews Varghese, Francesca Vitali, Maria Ausilia Sciarrone, Francesca Alfano, Marco Luigetti","doi":"10.1007/s40120-026-01038-3","DOIUrl":"https://doi.org/10.1007/s40120-026-01038-3","url":null,"abstract":"<p><p>Paraneoplastic neuropathies are rare, immune-mediated disorders caused by an antitumor immune response that cross-reacts with components of the peripheral nervous system, such as peripheral nerves and dorsal root ganglia. Unlike syndromes associated with antibodies targeting neuronal surface or extracellular antigens, in which auto-antibodies are considered directly pathogenic, neurological syndromes associated with intracellular onconeural antigens are predominantly mediated by cytotoxic T-cell responses. Accurate diagnosis of these syndromes relies on early identification of high-risk clinical phenotypes, combined with appropriate serum and cerebrospinal fluid antibody testing, neurophysiological investigations, imaging, and a comprehensive differential diagnostic work-up. Current treatment is primarily based on tumor control and immunomodulatory or immunosuppressive therapies. Nevertheless, no treatment has demonstrated consistent efficacy in neurological syndromes associated with intracellular onconeural antigens, particularly once irreversible neuronal damage has occurred. Emerging strategies, including chimeric antigen receptor T-cell therapies and agents targeting T-cell activation or co-stimulatory pathways, warrant further investigation. Close collaboration between neurologists and oncologists is therefore essential to improve early diagnosis, therapeutic management, functional outcomes, and prognosis.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}