Expert Review of Neurotherapeutics最新文献

{"title":"The complexities of diagnosing young-onset Alzheimer's dementia and the need for swift identification.","authors":"Ann-Katrin Schild, Claudia Bartels, Richard Dodel","doi":"10.1080/14737175.2026.2733193","DOIUrl":"10.1080/14737175.2026.2733193","url":null,"abstract":"<p><strong>Introduction: </strong>Young-onset Alzheimer's disease (YOAD), defined by symptom onset before 65 years, represents a distinct subtype of Alzheimer's disease with important diagnostic and therapeutic implications. Compared with late-onset Alzheimer's disease (LOAD), YOAD shows greater phenotypic heterogeneity, more frequent atypical non-amnestic presentations, and a stronger genetic contribution, leading to a delay in diagnosis and a substantial psychosocial burden.</p><p><strong>Areas covered: </strong>This review summarizes the current evidence on epidemiology, genetics, clinical phenotypes, and diagnostic strategies. YOAD differs from LOAD in terms of broader differential diagnoses and atypical cognitive syndromes. Advances in biomarker-based diagnostics, neuroimaging, and blood-based markers, are discussed, with an emphasis on early detection, patient stratification, and relevance for emerging disease-modifying therapies. A systematic PubMed literature search covering the years 2010 to 2026, used search terms related to YOAD, clinical phenotypes, biomarkers, neuroimaging, and genetic factors.</p><p><strong>Expert opinion: </strong>YOAD remains underrecognized and diagnostically challenging, limiting timely access to targeted therapies. The integration of multimodal biomarkers and genetic testing is essential for early diagnosis, as is the need for a comprehensive neuropsychological assessment to capture atypical phenotypes. Future neurotherapeutic strategies also require age-specific approaches and the adaptation of health care systems to address the distinct clinical and socioeconomic needs in YOAD.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"923-941"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plain language summary of the mechanisms behind epilepsy in Alzheimer's disease and the use of perampanel.","authors":"Akira Kuzuya, Tomoyuki Ohara, Naoki Akamatsu","doi":"10.1080/14737175.2026.2733194","DOIUrl":"10.1080/14737175.2026.2733194","url":null,"abstract":"","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"1027-1035"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focused ultrasound blood-brain barrier opening: a review of post-procedure MRI outcomes.","authors":"Suzanne LeBlang, Rashi I Mehta, Pierre-François D'haese, Augusto Grinspan, Amit Sokolov, Giulia Frazzetta","doi":"10.1080/14737175.2026.2737272","DOIUrl":"https://doi.org/10.1080/14737175.2026.2737272","url":null,"abstract":"<p><strong>Introduction: </strong>Focused ultrasound (FUS) blood-brain barrier opening (BBBo) is an incisionless technique that facilitates cerebral drug delivery by temporarily increasing BBB permeability. Clinical trials have shown that FUS produces reversible BBBo and is feasible in humans. There are currently no standardized imaging protocols for assessing the safety of FUS-BBBo, although MRI is commonly performed.</p><p><strong>Areas covered: </strong>This structured narrative review summarizes neuroimaging techniques used to assess FUS-BBBo safety in clinical trials of participants with neurological disorders that reported post-procedural MRI findings. A search of PubMed from September 2014 to April 2026 was undertaken to identify clinical trials of FUS-BBBo (13 in patients with brain tumors and 16 in neurodegenerative diseases).</p><p><strong>Expert opinion: </strong>Localized T2* hypointense signals and T2 hyperintense signals are relatively common after FUS-BBBo. While these findings have been thought to be related to transient microhemorrhage or edema, no consistent association has been found between such findings and clinically significant adverse events. Further work incorporating standardized post-FUS-BBBo MRI safety assessments is needed to clarify the biological significance of these signal alterations, and to determine whether they indicate a potential long-term safety concern, are a harmless finding associated with the BBBo procedure, or are associated with the underlying diseases and/or concomitant drugs.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"1-13"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical implications of anosognosia in Alzheimer's disease.","authors":"Valentina Moro, Greta Vianello, Giuseppe Gambina, Valeria Gobbetto, Marina Gasparini, Maddalena Beccherle","doi":"10.1080/14737175.2026.2726416","DOIUrl":"10.1080/14737175.2026.2726416","url":null,"abstract":"<p><strong>Introduction: </strong>Assessing awareness of patients with Alzheimer's disease (AD) is essential for diagnosis and treatment. Anosognosia, defined as impaired awareness of cognitive and functional deficits, is associated with poorer prognosis, reduced decision-making capacity, increased risk of accidents, and earlier institutionalization.</p><p><strong>Areas covered: </strong>This narrative review examines 53 studies. After outlining the main theoretical models of awareness in dementia, the multidimensional nature of anosognosia and its impact on patients' autonomy and decision-making abilities are discussed. This review also describes the main instruments available for assessing awareness deficits and highlights their relevance in clinical practice. Particular attention is given to the implications of anosognosia for treatment adherence, patient care, and decision making.</p><p><strong>Expert opinion: </strong>Taking care of unaware AD patients represents a challenge, and anosognosia is often underestimated in clinical practice. Evidence suggests that awareness deficits may emerge even in the earliest stages of AD, affecting patients' autonomy and capacity to make informed decisions. A two-step assessment process is recommended, consisting of an initial screening followed by a comprehensive evaluation carried out by specialized neuropsychologists. Targeted caregiver training is also essential to address the challenges associated with impaired awareness.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"943-955"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The recognition, diagnosis, and management of late-onset bipolar disorder.","authors":"Bruno Lancksweerdt, An Van Duyse, Bernard Sabbe","doi":"10.1080/14737175.2026.2727099","DOIUrl":"10.1080/14737175.2026.2727099","url":null,"abstract":"<p><strong>Introduction: </strong>Late-onset bipolar disorder (LOBD) represents a clinically relevant but understudied subtype of bipolar. Compared with early-onset bipolar disorder, LOBD may present with distinct clinical features, increased somatic comorbidity, and potential associations with neurodegenerative and vascular processes. Specific diagnostic and therapeutic recommendations for LOBD are currently limited.</p><p><strong>Areas covered: </strong>This narrative review examines the current evidence regarding epidemiology, pathophysiology, diagnostic workup, and management of LOBD. Literature was identified using PubMed to conduct a structured literature search of the MEDLINE database for articles between 2015 and 2025, and review of relevant articles. Particular attention is given to differential diagnosis with secondary mania and neurodegenerative disorders, the role of medical and neurological evaluation, and treatment considerations including pharmacological strategies, neuromodulation, psychosocial interventions, and longitudinal follow-up.</p><p><strong>Expert opinion: </strong>Current evidence suggests that LOBD likely represents a heterogeneous condition with multiple underlying mechanisms, including vascular burden, neurodegenerative processes, and age-related biological vulnerability. Comprehensive somatic and cognitive assessment is essential. While treatment generally follows established bipolar disorder guidelines, careful adaptation is required due to comorbidity, polypharmacy, and age-related pharmacodynamic changes. Lithium, with its potential neuroprotective properties, may be the first-choice medication. Future research should focus on clarifying pathophysiological mechanisms and developing tailored management strategies.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"971-983"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing insights into fibromyalgia: an updated review of diagnosis and differential diagnosis.","authors":"Víctor Segura-Jiménez","doi":"10.1080/14737175.2026.2733188","DOIUrl":"10.1080/14737175.2026.2733188","url":null,"abstract":"<p><strong>Introduction: </strong>Despite advances in understanding nociplastic pain and central sensitization, fibromyalgia remains a challenging clinical diagnosis due to the absence of specific biomarkers, extensive symptom overlap with other conditions, and persistent misconceptions about its pathophysiology.</p><p><strong>Areas covered: </strong>This narrative review covers the evolution of the diagnostic criteria, the clinical presentation, the red flags suggesting alternative diagnoses, and a practical diagnostic approach toward fibromyalgia. Attention is given to its differential diagnosis with rheumatological, neurological, endocrine, sleep, and psychiatric conditions as well as other overlap syndromes, along with emerging tools including quantitative sensory testing, small fiber pathology, neuroimaging, and digital phenotyping. Evidence was identified through a search of PubMed and Web of Science (April to May 2026) for 'fibromyalgia' combined with key terms, supplemented by hand-searching reference lists and recent systematic reviews.</p><p><strong>Expert opinion: </strong>Fibromyalgia should be approached not as a diagnosis of exclusion but as a recognizable nociplastic pain syndrome requiring mechanism-informed evaluation. In practice, this means applying the American College of Rheumatology 2010/2016 criteria positively, limiting work-up to a five-test panel (complete blood count, erythrocyte sedimentation rate, C-reactive protein, thyroid-stimulating hormone, and creatine kinase if weakness is present) unless red flags dictate otherwise, and only when diagnostic uncertainty, red flags, or overlapping inflammatory disease persist.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"985-1003"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric multiple sclerosis: a diagnostic overview and the importance of early identification.","authors":"Monica Margoni, Massimo Filippi, Maria A Rocca","doi":"10.1080/14737175.2026.2726418","DOIUrl":"10.1080/14737175.2026.2726418","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric-onset multiple sclerosis (POMS) is uncommon but clinically relevant, as inflammatory demyelination occurs during brain maturation. Compared with adult-onset MS, POMS is characterized by higher early relapse rate and MRI inflammatory activity, better recovery from individual relapses, yet disability milestones are reached at a younger age. Early identification is essential to avoid treatment delays, while preventing misdiagnosis of mimics.</p><p><strong>Areas covered: </strong>This review summarizes the diagnostic work-up of children with a first acquired demyelinating syndrome, differential diagnosis, the role of MRI, cerebrospinal fluid (CSF) markers, antibody testing, serum neurofilament light chain, optical pathway assessment and the 2024 McDonald criteria. Early prognostic factors and therapeutic implications are discussed, including evidence supporting early high-efficacy therapies in selected children. References for this review were identified through searches of PubMed, authors' own files, abstracts presented at main congresses, from 1 January 1979 to 1 July 2026.</p><p><strong>Expert opinion: </strong>Early identification of POMS requires integrated assessment of clinical presentation, MRI lesion topography, CSF findings, antibody testing, and emerging biomarkers. Although central vein sign, paramagnetic rim lesions, kappa free light chains and serum neurofilament light chain may refine stratification, pediatric validation remains incomplete. Earlier, more accurate diagnosis should support individualized treatment to preserve long-term outcomes.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"957-970"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HAND-IN (hand function after neuromodulation and intensive training in children with cerebral palsy): study protocol for a randomized, triple-blind, controlled trial with embedded implementation and cost-effectiveness analyses.","authors":"Andréa Vancetto Maglione, Juliana Firmo Dos Santos, Ana Carolina Rodrigues da Silva, Lais Ester Roveron Souto, Gabriela da Silva Matuti, Elcinete Wentz Moura, Maristela Costa Cespedes, Carina Gonçalves Pedroso Uchida, Acary Souza Bulle Oliveira, Sandra Regina Alouche","doi":"10.1080/14737175.2026.2727670","DOIUrl":"10.1080/14737175.2026.2727670","url":null,"abstract":"<p><strong>Aim: </strong>The following clinical trial protocol aims to investigate the additional effects of bilateral transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) compared to CIMT alone in children and adolescents with spastic hemiparetic cerebral palsy.</p><p><strong>Methods: </strong>This randomized, triple-blind, controlled trial will enroll 32 participants aged 7-16 years with spastic hemiparetic cerebral palsy (MACS I-II). Participants will be allocated to CIMT with sham or active bilateral tDCS (C3-C4, 1 mA, 20 min), with electrode placement guided by transcranial magnetic stimulation mapping. The intervention will last 3 weeks (5 days/week, 3 h/day). Primary outcomes will assess upper limb use (PMAL/TMAL). Secondary outcomes include dexterity (Box and Block Test), strength (dynamometry), functional performance (PAFT), and participation (COPM, GAS). Assessments will occur post-intervention and at 1, 3, and 6 months. Implementation of outcomes and cost-effectiveness will also be evaluated. Once completed, the study team will perform intention-to-treat analyses using linear mixed-effects models.</p><p><strong>Expected results: </strong>The HAND-IN trial will provide evidence on the clinical, implementation, and economic effects of combining CIMT with bilateral tDCS in children with spastic hemiparetic cerebral palsy. If effective, this approach may enhance the durability of upper limb functional gains and support the adoption of neuromodulation in pediatric neurorehabilitation.<b>Trial Registration Number (Brazilian Clinical Trials Record- REBEC)</b>: RBR-2fczbt2 (https://ensaiosclinicos.gov.br/rg/RBR-2fczbt2). Registration on January 15, 2026.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"1017-1026"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy with myoclonic-atonic seizures: a comprehensive review with emphasis on current and emerging pharmacotherapies.","authors":"Debopam Samanta","doi":"10.1080/14737175.2026.2735961","DOIUrl":"https://doi.org/10.1080/14737175.2026.2735961","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy with myoclonic-atonic seizures (EMAtS), historically termed Doose syndrome, is a developmental and epileptic encephalopathy characterized by the usually abrupt onset of multiple generalized seizure types, including myoclonic-atonic seizures, in early childhood. Advances in genetic diagnostics, antiseizure treatments, and precision therapies have reshaped understanding and management of EMAtS.</p><p><strong>Areas covered: </strong>This review synthesizes the clinical spectrum of EMAtS, including core clinical features and diagnostic approach based on a literature search of PubMed, Embase, and OVID/MEDLINE. The genetic landscape is discussed to contextualize emerging precision therapies. Treatment is reviewed hierarchically, from valproate, clobazam, levetiracetam and ethosuximide as commonly used first- and second-line agents to the ketogenic diet, cannabidiol, felbamate, and sulthiame for drug-resistant disease. Precision approaches for key genetic etiologies, including<i>SLC2A1, SLC6A1, SYNGAP1, CHD2, STXBP1</i>,and<i>SCN2A</i>, are also reviewed.</p><p><strong>Expert opinion: </strong>Although approximately two-thirds of patients with EMAtS achieve seizure remission, a substantial minority experience drug-resistant seizure, intellectual disability, and behavioral comorbidities, underscoring the importance of timely diagnosis, appropriate pharmacotherapy, and early consideration of the ketogenic diet in drug-resistant cases. As precision therapeutics advance, syndrome-based care will increasingly be complemented by treatments tailored to the specific genetic etiology.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic radiosurgery for craniofacial pain disorders: current clinical applications and future perspectives.","authors":"Andrea Franzini, Emanuele Stucchi, Alessandro Grimi, Generoso Farinaro, Ali Baram, Beatrice Claudia Bono, Zefferino Rossini, Maria Pia Tropeano, Piero Picozzi, Federico Pessina","doi":"10.1080/14737175.2026.2735964","DOIUrl":"https://doi.org/10.1080/14737175.2026.2735964","url":null,"abstract":"<p><strong>Introduction: </strong>Stereotactic radiosurgery (SRS) has emerged as a less invasive treatment for various medically refractory craniofacial pain disorders. Advances in neuroimaging, radiosurgical technology, and treatment planning have expanded its application beyond trigeminal neuralgia (TN) to glossopharyngeal neuralgia (GN), trigeminal autonomic cephalalgias (TACs), and neuropathic facial pain (NFP).</p><p><strong>Areas covered: </strong>This review summarizes the current clinical indications, radiosurgical techniques, efficacy, safety, and limitations of SRS for medically refractory craniofacial pain disorders. The available literature on TN, GN, TACs, and NFP is reviewed, with particular emphasis on patient selection, target definition, treatment outcomes, repeat radiosurgery, and treatment-related adverse effects.</p><p><strong>Expert opinion: </strong>SRS is an established treatment for classical, idiopathic, and multiple sclerosis-related TN. In contrast, its application to GN, tumor-related TN, TACs, and NFP remains investigational because of limited and heterogeneous evidence. Future advances in neuroimaging, target localization, and understanding of craniofacial pain pathophysiology, together with well-designed studies, are expected to optimize patient selection and better define the role of SRS for those disorders.</p>","PeriodicalId":12190,"journal":{"name":"Expert Review of Neurotherapeutics","volume":" ","pages":"1-14"},"PeriodicalIF":4.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}