Neurology International最新文献

{"title":"Auricular Vagus Nerve Stimulation Combined with Physical Therapy for Individuals with Parkinson's Disease: A Pilot Randomized Sham-Controlled Trial.","authors":"Alexandra Evancho, Jennifer Dawson, Harrison C Walker, Christopher G Ballmann, William J Tyler","doi":"10.3390/neurolint18060118","DOIUrl":"10.3390/neurolint18060118","url":null,"abstract":"<p><p><b>Background:</b> Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson's disease. To date, no studies have examined the integration of transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, tolerability, and feasibility of combining taVNS with physical therapy to enhance the therapeutic benefits of exercise as medicine in a clinical setting. <b>Methods:</b> Participants were randomly assigned to receive active or sham bilateral taVNS in combination with PT for 12 visits over 6 weeks. Safety, tolerability, and feasibility outcomes were primary. Secondly, exploratory analyses of changes in cardiovascular and motor function over time were also performed. <b>Results:</b> Overall, taVNS was safe and well-tolerated prior to PT. Cardiovascular analyses suggest that active taVNS may augment HR response to exercise compared to sham. For motor outcomes, both groups showed significant overall improvements; however, no significant between-group differences were found. <b>Conclusions:</b> The preliminary results obtained in this pilot trial confirm that taVNS combined with physical therapy for individuals with PD is safe and feasible. The exploratory cardiovascular and motor findings support the need for larger, adequately powered clinical trials investigating the integration of taVNS into PT and exercise methods for improving PD symptomology. Trial registration: ClinicalTrials.gov NCT05871151.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Global Burden Perspective on Obstructive Sleep Apnea, Hearing Loss, and Early-Onset Cognitive Decline.","authors":"Alice Tomaselli, Antonina Luca, Mario Lentini, Jerome Rene Lechien, Federico Mollame, Alberto Caranti, Claudio Vicini, Matteo Lazzeroni, Pasquale Capaccio, Giannicola Iannella, Valentin Favier, Antonino Maniaci","doi":"10.3390/neurolint18060117","DOIUrl":"10.3390/neurolint18060117","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cognitive decline and dementia represent a growing global crisis, affecting over 57 million individuals worldwide, projected to exceed 150 million by 2050. The 2024 Lancet Commission identified hearing loss as the single largest modifiable dementia risk factor (~7% population-attributable fraction). Obstructive sleep apnea (OSA), affecting ~936 million adults, is an increasingly recognized contributor yet remains underdiagnosed, especially in low- and middle-income countries (LMICs). This review synthesizes evidence on the global burden of cognitive decline associated with both conditions, evaluates causality debates, and identifies research gaps. <b>Methods</b>: Following SANRA guidelines, a search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library through February 2026. Original studies, systematic reviews, meta-analyses, and WHO/GBD reports were included; editorials and non-English publications were excluded. After deduplication, 3847 records were screened, and 96 studies met the inclusion criteria. <b>Results</b>: OSA has been linked to cognitive decline through several plausible mechanisms, including intermittent hypoxia, sleep fragmentation, impaired glymphatic clearance, and amyloid-beta accumulation, though the directionality of these associations requires confirmation from longitudinal studies. Hearing loss contributes to cognitive load, social isolation, and cortical reorganization. Both conditions disproportionately affect LMICs, where access to diagnosis and treatment remains limited. CPAP and hearing rehabilitation show cognitive benefits when initiated early, though evidence for reversing established impairment remains limited. A synergistic interaction between the two conditions is biologically plausible but empirically underexplored. <b>Conclusions</b>: OSA and hearing loss are highly prevalent conditions associated with increased dementia risk, though the certainty of causal relationships and the magnitude of intervention effects differ between the two conditions and across the available evidence. Integrated screening and early intervention could yield substantial neuroprotective benefits in high-risk populations and LMICs. Future longitudinal studies should examine combined cognitive trajectories and optimal intervention timing.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13304768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenecteplase With or Without Mechanical Thrombectomy in Acute Ischemic Stroke at 4.5 to 24 h: An Updated Meta-Analysis of Randomized Controlled Trials.","authors":"Beatrice Dell'Acqua, Carmelina Maria Costa, Andrea Cerri, Alessandro Francia, Simone Vidale","doi":"10.3390/neurolint18060116","DOIUrl":"10.3390/neurolint18060116","url":null,"abstract":"<p><strong>Background and purpose: </strong>Tenecteplase (TNK) within 4.5 h from symptom onset is not inferior to alteplase in treating ischemic stroke. In recent years, some randomized controlled trials (RCTs) have investigated the efficacy of extending the therapeutic window up to 24 h. This updated meta-analysis aims to synthesize the results of these RCTs comparing TNK to the best medical treatment (BMT) with or without endovascular thrombectomy.</p><p><strong>Methods: </strong>In accordance with PRISMA guidelines, all RCTs comparing TNK with BMT in adult patients between 4.5 and 24 h were systematically searched. The primary endpoint was good functional outcome at 90 days (mRS 0-2). Secondary endpoints included excellent outcome (mRS 0-1), symptomatic intracerebral hemorrhage (sICH), 90-day mortality, complete reperfusion at 24 h. Odd and Hazard ratios (ORs; HRs) were pooled using meta-analytic methods.</p><p><strong>Results: </strong>A total of seven RCTs involving 1754 patients were included. The rates of the primary endpoint were higher in TNK-treated patients (HR: 1.15; 95% CI: 1.03-1.27), as were rates of excellent functional outcome (HR: 1.29; 95% CI: 1.08-1.55). In the subgroup receiving intravenous therapy (IVT) alone, the primary endpoint was significantly more frequent in the TNK group than in the BMT group (OR: 1.47; 95% CI: 1.17-1.84; <i>p</i> for heterogeneity < 0.0001). TNK treatment was also associated with higher reperfusion rates compared with BMT, reflecting a greater proportion of saved ischemic penumbra as assessed via perfusion imaging. Although symptomatic intracranial hemorrhage (sICH) occurred more frequently in TNK-treated patients, the difference did not reach statistical significance, and mortality rates were comparable between treatment groups.</p><p><strong>Conclusions: </strong>Tenecteplase administered between 4.5 and 24 h is associated with improved rates of both good and excellent functional outcomes compared with BMT, especially in patients treated with IVT alone. Additionally, TNK is linked to higher rates of reperfusion.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13304984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of ABO Blood Group on Vascular Complications and on Clinical and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.","authors":"Vera Marschal, Andreas Ziebart, Maryam Abdoullahi, Daniel Werkmann, Ralph König, Thomas Kapapa, Benjamin Mayer, Johannes Rosskopf, Lennart Marschal, Christian Rainer Wirtz, Andrej Pala, Gregor Durner","doi":"10.3390/neurolint18060115","DOIUrl":"10.3390/neurolint18060115","url":null,"abstract":"<p><p><b>Objective</b>: To evaluate whether ABO blood group is associated with venous thromboembolic events (VTEs), cerebral severe vasospasm (CSV), delayed cerebral ischemia (DCI), and clinical or cognitive outcomes after aneurysmal subarachnoid hemorrhage (aSAH). <b>Materials and Methods</b>: A retrospective observational two-center cohort study of collected registry data, including 169 patients treated between September 2021 and November 2025. Outcomes were compared across ABO subtypes using univariate testing and multivariable logistic regression. <b>Results</b>: No ABO subtype was independently associated with VTE (7.7%), CSV/DCI (21.9%), intracranial hemorrhage, or in-hospital mortality (all <i>p</i> > 0.05). Higher age (OR 1.08, 95% CI 1.031-1.144, <i>p</i> = 0.003) was independently associated with increased in-hospital mortality, whereas single peri-interventional antiplatelet therapy (PIAT) (OR 0.076, 95% CI 0.004-0.506, <i>p</i> = 0.029) was associated with lower in-hospital mortality. ABO blood group was not associated with functional outcome (mRS) or cognitive performance (MoCA) in this cohort. <b>Conclusions</b>: In this two-center retrospective cohort, no independent association between ABO blood group and early cerebrovascular complications, functional outcome, or cognitive outcome after aSAH was detected. These findings suggest that short-term prognosis may be more strongly influenced by established patient- and treatment-related factors, particularly age and single PIAT. Further studies with larger cohorts are warranted to clarify the potential effect of ABO blood group on outcomes after aSAH.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neuroprotective Role of Exercise in Alzheimer's Disease: An Integrative Review of Animal and Human Studies.","authors":"Danqing Xiao, Akshita Duvvuri, Lenna V Makrigiannis, Catherine Fuller","doi":"10.3390/neurolint18060113","DOIUrl":"10.3390/neurolint18060113","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the leading cause of dementia, is characterized by progressive cognitive decline along with hallmark brain pathologies including amyloid-beta accumulation, hyperphosphorylated tau, neuroinflammation and neuronal mitochondrial dysfunction. As current pharmaceutical treatments only provide modest symptomatic improvement, there is an urgent need for effective non-pharmaceutical treatment options for the prevention or slowing down of this disease. This review synthesizes results from randomized controlled trials, observational studies, and animal model research on the ability of exercise to influence cognitive functions, brain structural changes, inflammatory processes, and neuroplasticity-related pathways. Exercise has demonstrated the capacity to enhance neurotrophic signaling, improve the regulation of mitochondria, improve cerebrovascular function and reduce pro-inflammatory cytokine levels in preclinical and mild cognitive impairment (MCI) subjects. Additionally, aerobic and resistance training has been shown to enhance physical performance and functional capacity. Furthermore, mind-body, dual-task and multimodal types of interventions may also provide additional cognitive and psychological benefits. Although the overall cognitive effect of exercise in individuals with established AD is generally small, it has been demonstrated that exercise can contribute to maintaining brain health through multiple interconnected metabolic, vascular and molecular pathways, thereby preserving cognitive reserve and slowing disease progression, particularly when initiated during early to midlife prior to the onset of AD symptoms. Therefore, future research will require establishing stage-specific exercise recommendations based on modality type, intensity and duration to achieve optimal clinical outcomes.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Regulation of the NET Formation-Blood-Brain Barrier Axis in Ischemic Stroke: Mechanisms, Therapeutic Targets and Translational Perspectives.","authors":"Kirti Sharma, Baani Singh, Sarabjit Mastana, Monica Singh, Puneetpal Singh","doi":"10.3390/neurolint18060114","DOIUrl":"10.3390/neurolint18060114","url":null,"abstract":"<p><p>Ischemic stroke elicits a rapid and sustained innate immune response that critically contributes to blood-brain barrier (BBB) breakdown and secondary neuronal injury. Among the cellular mediators involved, neutrophil extracellular traps (NETs) have emerged as potent effectors of neurovascular damage. However, the regulatory mechanisms governing NET formation and their prolonged impact on BBB integrity remain incompletely understood. Increasing evidence indicates that NET formation is an epigenetically regulated process, requiring chromatin remodeling, histone modifications, DNA methylation changes and non-coding RNA-mediated control within neutrophils under ischemic conditions. These epigenetic events license the extrusion of DNA-histone-enzyme complexes that directly injure endothelial cells, degrade tight junction proteins, activate innate immune signaling pathways and amplify neuroinflammatory cascades at the neurovascular unit. Moreover, NET-derived chromatin and associated mediators can induce transcriptional and epigenetic alterations in BBB cells, thereby sustaining barrier permeability and impairing vascular repair mechanisms. In this review, we synthesize current knowledge on the epigenetic regulation of NET formation and delineate how epigenetically regulated NETs function as key disruptors of BBB integrity in ischemic stroke. Understanding this NETosis-epigenetics-BBB axis may uncover novel therapeutic strategies aimed at preserving neurovascular integrity and limiting post-stroke brain injury.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13304689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-Binding Proteins in Ageing and Age-Related Disease.","authors":"João Miguel Alves Ferreira, Sergii Tukaiev, Vaitsa Giannouli","doi":"10.3390/neurolint18060112","DOIUrl":"10.3390/neurolint18060112","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid-liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium-Induced Toxicity as a Pathophysiological Mechanism for Parkinson's Disease Onset in Individuals with Iron and Zinc Deficiencies and Chronic Obstructive Pulmonary Disease.","authors":"Milan Aksic, Ana Cirovic, Orish Ebere Orisakwe, Vuk Djulejic, Bruna Puty, Rafael Rodrigues Lima, Aleksandar Cirovic","doi":"10.3390/neurolint18060111","DOIUrl":"10.3390/neurolint18060111","url":null,"abstract":"<p><p>The pathophysiological basis of Parkinson's disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson's disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson's disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency-known risk factors for Parkinson's disease-lead to an increased cadmium burden and contribute to the onset and progression of the disease.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executive Function Profiles in ADHD and Dyslexia: A Mixed-Method Neurocognitive Analysis.","authors":"Geanina Cucu Ciuhan","doi":"10.3390/neurolint18060110","DOIUrl":"10.3390/neurolint18060110","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Executive function (EF) impairments are common in neurodevelopmental disorders but are often examined using group-level approaches that may overlook clinically meaningful cognitive heterogeneity. This study explored EF heterogeneity in children with attention deficit hyperactivity disorder (ADHD), developmental dyslexia, and comorbid presentations using a clinically grounded mixed-method approach. <b>Methods</b>: Standardized neuropsychological data from the NEPSY-II, WISC-IV, and Woodcock-Johnson IV batteries were integrated with a case-based thematic synthesis of 11 clinical evaluations. Semi-inductive analysis was informed by preliminary patterns observed in a larger clinical sample. <b>Results</b>: Three executive function profiles were identified: (1) globally reduced executive functioning, characterized by widespread deficits in inhibition, attention, and working memory; (2) verbal-mnestic executive vulnerability, marked by weaknesses in verbal memory and attention regulation despite relative cognitive strengths; and (3) selective executive control deficit, reflecting impairments in inhibitory control and self-regulation. These profiles revealed clinically meaningful patterns that were not fully captured by categorical diagnostic classifications. <b>Conclusions</b>: The findings support the value of integrated, profile-based approaches for understanding executive function heterogeneity in neurodevelopmental conditions. Such approaches may enhance ecological validity in assessment and contribute to individualized intervention planning. Given the exploratory and case-based nature of the study, the findings should be considered preliminary and hypothesis-generating.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Neurological Disorder: Neurobiological Mechanisms, Biomarkers, and Integrated Treatment in a Female-Predominant Neuropsychiatric Condition.","authors":"Giuseppe Marano, Marianna Mazza","doi":"10.3390/neurolint18060109","DOIUrl":"10.3390/neurolint18060109","url":null,"abstract":"<p><strong>Background: </strong>Functional Neurological Disorder (FND) is a common and disabling condition at the interface of neurology and psychiatry, characterized by motor, sensory, seizure-like, or cognitive symptoms that are incongruent with recognized neurological disease but associated with substantial impairment. Despite its frequency and marked female predominance, FND remains underdiagnosed and often misunderstood.</p><p><strong>Methods: </strong>This narrative review synthesizes evidence from neurobiological, biomarker, and treatment studies, with attention to predictive coding, salience network dysfunction, impaired sense of agency, stress-related mechanisms, and sex- and gender-related vulnerability.</p><p><strong>Results: </strong>Current evidence supports a model of FND as a disorder of distributed brain network dysfunction involving abnormal interactions among salience, limbic, motor, and self-monitoring systems. Predictive coding and impaired agency models provide clinically useful frameworks for understanding symptom generation, although they remain mechanistic hypotheses rather than definitive causal explanations. Candidate biomarkers, including functional connectivity alterations, autonomic dysregulation, and HPA axis measures, offer pathophysiological insight but remain insufficiently validated for routine diagnosis. Female predominance likely reflects interacting biological, psychological, and sociocultural mechanisms rather than a single neuroendocrine pathway.</p><p><strong>Conclusions: </strong>This review contributes an integrated, clinically oriented framework linking neurobiology, biomarkers, sex/gender vulnerability, and treatment in FND. Current evidence supports multidisciplinary care combining diagnostic communication, specialized physiotherapy, psychotherapy, and coordinated follow-up, while future research should prioritize standardized phenotyping, longitudinal designs, and multimodal biomarker validation.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"18 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}