Neurology International doi: 10.3390/neurolint18110217

Authors: Ayaulym Nagashybay Assanali Tokenov Medet Mukushev Guzel Shider Feruza Sultamuratova Beibit Abdikenov Aisha Zhantleuova Marzhan Lepesova Almira M. Kustubayeva Altynay Karimova

Background/Objectives: Parkinson’s disease (PD) is a rapidly growing cause of neurological disability, yet diagnosis is often delayed in settings with limited access to movement-disorder specialists, including Kazakhstan and other Central Asian countries. This study aimed to develop a brief, self-administered, two-stage machine-learning-derived questionnaire based on binary symptom responses to identify individuals with possible clinically manifest PD who may benefit from specialist neurological assessment, and to evaluate its performance. Methods: From outpatient records of 402 patients with confirmed PD, a preliminary 100-item yes/no questionnaire was compiled. In a development cohort of 389 participants aged 60 to 90 years (146 with PD, 243 controls) recruited in Almaty, Kazakhstan, we used ElasticNet logistic regression, random forest, and gradient boosting to select features, reducing the instrument to 35 items (15 in Stage 1, 20 in Stage 2). We assessed performance on a held-out test set (n = 78) and in an interim prospective external-validation cohort (n = 290) recruited independently, with neurologists blinded to questionnaire results. Results: On the held-out test set, sensitivity was 86.2%, specificity 89.8%, accuracy 88.5%, and Stage 1 AUC 0.9557. In the interim external validation, sensitivity was 95.1%, specificity 94.4%, accuracy 94.5%, NPV 99.2%, and Stage 1 AUC 0.9962; only 12.1% of participants required Stage 2. Conclusions: The two-stage questionnaire showed strong case-finding ability in identifying individuals who warrant neurological evaluation. Findings are interim; completion of external validation, larger geographically diverse cohorts, and comparison against existing instruments are needed before wider implementation.

Neurology International doi: 10.3390/neurolint18110216

Authors: Sonu Bhaskar

Successful recanalisation after acute ischaemic stroke does not guarantee neurological recovery. The Time, Tissue, and Systems (TTS) framework conceptualises outcomes as interactions among elapsed time, tissue vulnerability (including collateral status and microvascular integrity), and healthcare system performance. Recent evidence, including the LATE-MT trial, supports imaging-selected thrombectomy beyond 24 h, yet approximately half of patients experience so-called futile recanalisation. This Special Issue addresses the optimisation of reperfusion, tissue-level protection, and sustained recovery, with a special focus on distinguishing angiographic from tissue-level reperfusion, aligning neuroprotection with biological phenotypes, incorporating cognition and participation as clinical endpoints, and strengthening equitable systems of care. This framework provides an organising perspective for translating these advances into improved patient-centred outcomes.

Neurology International doi: 10.3390/neurolint18110215

Authors: Daniele Orsucci Lucia Picchi Ilaria Di Donato Marco Vista Martina Giuntini

Huntington disease (HD) is a complex neurogenetic disorder requiring coordinated, multidisciplinary management across disease stages. This narrative review summarizes the clinical features, genetic counselling, symptomatic pharmacological treatments, rehabilitation, swallowing and nutritional management, psychological care, and social support needs of individuals with HD. Particular attention is given to locally coordinated healthcare services and the role of the neurologist in facilitating multidisciplinary care. The literature-based discussion is complemented by a descriptive summary of 15 individuals evaluated in our local neurological services during the preceding year. These individuals showed considerable heterogeneity in clinical manifestations, functional disability, and care needs. Six of 15 individuals (40%) had at least one documented refusal or postponement involving heterogeneous recommended interventions. This observation was descriptive and was not intended as a standardized measure of adherence or service uptake. Integrated care requires regular reassessment, individualized treatment planning, effective communication among healthcare professionals, and sustained support for patients and families. Although the organization of care varies across healthcare systems, accessible local expertise and collaboration with specialist referral centres may help reduce fragmentation and promote continuity of care throughout the disease course.

Neurology International doi: 10.3390/neurolint18110214

Authors: Ayah Erjan Sakhr Alshwayyat Rema' Aljedi Anisa Al Jabri Wafa Asha Mouness Obeidat Maysa Al-Hussaini Abdelatif Almousa

Background: Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare neoplasms with limited outcome data. We describe our institutional experience with adult CNS SFTs. Methods: We retrospectively reviewed adults (≥18 years) with histopathologically confirmed CNS SFTs treated at a tertiary referral center between 2005 and 2023. Clinical, radiologic, pathologic, treatment, and follow-up data were collected from the electronic medical record, and pathology was centrally reviewed. Results: Twelve patients were included. Median age at diagnosis was 38 years (range, 18–52), and 58.3% were male. The cohort included 11 intracranial tumors and 1 primary spinal tumor. WHO Grade 3 tumors were most common (n = 6, 50%). Initial treatment with subtotal resection was performed in six patients (50%), gross total resection in five (41.7%), and biopsy alone in one (8.3%). Adjuvant radiotherapy was administered in 58.3% (n = 7), and chemotherapy in one of the two patients with extracranial relapse. Six patients (50%) developed local recurrence, and two (16.7%) experienced extracranial relapse. Five- and ten-year overall survival rates were both 91.7%, and five- and ten-year recurrence-free survival rates were 73.3% and 50.3%, respectively. With a median follow-up of 12 years, late events included extracranial metastases at 8.9 and 9.4 years, and local recurrences at 11.1 and 17.2 years. Conclusions: CNS SFTs in adults show frequent local relapse and disease events more than a decade after treatment. Prolonged surveillance is warranted, and larger multicenter studies are needed to define prognostic factors and optimal treatment.

Neurology International doi: 10.3390/neurolint18110213

Authors: Ken Kitai Kaichi Nishigaya Yasuhisa Mizomoto Hiroki Ito Ryosuke Yamauchi Osamu Katayama Shin Murata Takayuki Kodama

Background/Objectives: Post-stroke impairment (PSI) frequently causes upper limb sensorimotor deficits, including reduced ability to perceive fingertip friction, limiting dexterous movements. We evaluated the effects of a tactile sensory substitution device (“Yubi-Reco”) that delivers real-time fingertip friction information to both temporal bones via vibration and explored potential neurophysiological changes in PSI. Methods: This study used a single-case experimental multiple-baseline design. Three participants with PSI completed a 15-day AB-phase protocol. Baseline (A) consisted of daily sensorimotor tasks without Yubi-Reco, while the intervention (B) added real-time friction feedback via Yubi-Reco to the same tasks. Outcomes included electroencephalography (gamma power), the Purdue Pegboard Test, finger numbness Numerical Rating Scale (NRS), Motor Activity Log-14 (Amount of Use [AoU], Quality of Movement [QoM]), and sense of agency (SoA). Effect sizes were calculated using Tau-U. Results: Very large changes were observed in Purdue Pegboard Test performance (Tau-U = 0.80), and large changes were observed in finger numbness NRS scores (Tau-U = 0.79). Case I showed increased gamma power across frontal and central sites, Case II demonstrated relative attenuation near right frontal and parietal sites, and Case III showed bilateral central gamma reduction, suggesting neurophysiological alterations near recorded sites. AoU and SoA improved in all participants. AoU exceeded the minimal clinically important difference (0.5 points) in two cases. Conclusions: Real-time sensory substitution feedback using Yubi-Reco may improve upper-limb sensorimotor function and induce preliminary neurophysiological changes in individuals with PSI. The intervention appeared to enhance dexterous movement ability and SoA, which coincided with preliminary, exploratory neurophysiological shifts across sensorimotor networks.

Neurology International doi: 10.3390/neurolint18110212

Authors: Christian Schmidt Christian Hundeshagen Sabine Mihm

Background/Objectives: Parkinson’s disease (PD) is characterized by the selective loss of nigrostriatal dopaminergic neurons, accompanied by the accumulation and spreading of misfolded α-synuclein aggregates. Proposed mechanisms relevant to PD include gut–brain propagation of pathology via autonomic circuits, autophagy-related maintenance of proteostasis, and sleep-associated glymphatic clearance of extracellular waste. These mechanisms have prompted interest in multimodal approaches targeting disease-relevant biological pathways. Whether such approaches modify the neurodegenerative process or predominantly promote functional adaptation and compensation remains an open question. Methods: In a real-world clinical setting, a single patient with early-stage PD was observed over two years while five interventions targeting disease-relevant pathways were introduced at different time points and partly overlapped. Evaluation included physician-based clinical assessments and patient-reported observations, complemented by wearable-derived monitoring of autonomic and sleep metrics during the final six months. Serial DAT-SPECT imaging at baseline and two-year follow-up assessed changes in DAT binding. Results: Motor impairment remained mild and the patient reported largely stable overall mobility, although the persistent unilateral tremor was perceived to increase gradually later in the observation period. During the final six months, wearable monitoring indicated relative stable nocturnal autonomic measures and no markedly atypical rapid eye movement (REM) sleep estimates, while suggesting reduced slow-wave sleep (SWS). Following implementation of a structured bedtime routine, wearable-derived SWS estimates increased. Serial DAT-SPECT imaging demonstrated lower striatal DAT binding at two-year follow-up despite clinical stability. Conclusions: In this individual case, relative clinical stability coexisted with a longitudinal reduction in striatal DAT binding. Although no inference regarding disease modification can be drawn from a single uncontrolled observation, this discordance illustrates the limitations of interpreting clinical stability alone as evidence of an unchanged underlying disease process.

Neurology International doi: 10.3390/neurolint18110211

Authors: Aniket Kakkar Harpreet Singh Arvind Kumar Hitesh Chopra Arun Kumar Mishra Shivani Chopra Nigel H. Greig

Ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid peroxidation, has emerged as a potential contributor to neuronal dysfunction and degeneration in Alzheimer’s disease (AD). This review critically examines the biochemical basis, AD-specific evidence, chemical modulators, and therapeutic prospects of ferroptosis, emphasizing the distinction between mechanistic compatibility and causal demonstration. Ferroptotic susceptibility is governed by the balance among polyunsaturated phospholipid substrates, redox-active iron, lipid-peroxyl radical propagation, and enzymatic or chemical termination systems, including glutathione peroxidase 4 (GPX4), FSP1, and radical-trapping antioxidants. Human and experimental AD studies show brain iron accumulation, enhanced lipid peroxidation, impaired glutathione/GPX4 defenses, and disrupted iron export, but none establishes neuronal ferroptosis as the predominant mode of cell death. Two randomized trials of brain-penetrant iron chelation lowered the bulk brain iron signal and worsened clinical outcomes, which refutes the proposition that depleting bulk brain iron is therapeutic; because neither trial measured the kinetically labile iron pool, the mechanism of that harm remains undetermined. Among emerging strategies, membrane-active radical-trapping antioxidants and substrate-directed approaches offer mechanistically rational alternatives, whereas many natural products and multitarget agents remain difficult to interpret pharmacologically. Future studies should integrate cell-type-resolved redox lipidomics, direct target engagement, and rigorous causal intervention to determine whether ferroptosis or chronic sublethal lipid peroxidation is therapeutically actionable in AD.

Neurology International doi: 10.3390/neurolint18110210

Authors: Kenia R. Campanholo Lucas Alexandre S. Marzano Dagoberto Callegaro Tarso Adoni Guilherme Diogo Silva Maria Fernanda Mendes Daniele Costa O. Andrade Samira Luiza dos Apóstolos-Pereira

Background/Objectives: Cognitive impairment in neuromyelitis optica spectrum disorder (NMOSD) is increasingly recognized, but its profile and clinical correlates remain uncertain. This study sought to describe cognitive performance in individuals with NMOSD and to explore its associations with disease activity, disability level, and immunosuppressive treatment. Methods: This exploratory cross-sectional study characterized cognitive performance in 36 AQP4-IgG-positive individuals with NMOSD and 18 healthy volunteers using domain-level cognitive scores adjusted for age, education, and visual acuity. Results: Cognitive impairment was present in at least one domain in 27 participants, most frequently affecting memory (36%), praxis (33%), and information processing speed (IPS; 31%). IPS was the only domain significantly impaired in NMOSD compared with controls in unadjusted analyses (p = 0.007), but no domain remained significantly different after adjustment, despite a medium-to-large effect for IPS. Higher disability burden was associated with worse IPS (p = 0.011) and with lower scores on a clinically sensitive cognitive composite integrating memory, IPS, and executive function (β = –0.125, p = 0.040). Among clinical activity measures, annualized relapse rate showed a positive association only with executive function (β = 0.282, p = 0.007), whereas neither relapse count nor immunosuppressive treatment was associated with cognitive performance. Conclusions: These findings indicate a heterogeneous cognitive profile in NMOSD strongly influenced by demographic and sensory factors, with disability burden appearing to be more closely associated with cognitive performance than relapse-based activity.

Neurology International doi: 10.3390/neurolint18110209

Authors: Wataru Nukii Takamitsu Yamamoto Moe Fujita Ryota Nakamura Chikashi Fukaya Takahiro Fukazawa Reo Tsuchida Ryo Kasama Yu Miida Yuzumi Oda Masachika Niimi

Background/Objectives: High-frequency repetitive transcranial magnetic stimulation (rTMS) of the ipsilesional primary motor cortex is used to improve upper limb motor function after stroke. However, treatment responses vary among individuals. Contralesional corticospinal excitability and interhemispheric interactions may contribute to motor recovery. This study investigated the association between contralesional resting motor threshold (RMT) and improvement in upper limb motor function in patients receiving ipsilesional high-frequency rTMS combined with rehabilitation. Methods: This single-center retrospective observational study included 42 patients with poststroke upper limb hemiparesis. All patients received ipsilesional high-frequency rTMS combined with rehabilitation for 8 weeks. RMTs and Fugl-Meyer Assessment for Upper Extremity (FMA-UE) were evaluated at baseline. FMA-UE was reassessed after treatment. High-frequency rTMS was applied at 10 Hz, 1000 pulses per day, 6 days per week. Associations between contralesional RMT and change in FMA-UE score were assessed using Spearman’s rank correlation and multiple linear regression adjusted for baseline FMA-UE. Subgroup analyses were performed according to whether ipsilesional RMT could be determined within the predefined limit of 60% maximum stimulator output (MSO). Results: Contralesional RMT was positively correlated with change in FMA-UE score (ρ = 0.33, p = 0.033). Baseline-adjusted regression showed a positive association (B = 0.337, p = 0.029). However, sensitivity analyses indicated that these associations were not robust. Conclusions: Contralesional RMT may be associated with upper limb motor recovery in patients with subacute stroke receiving high-frequency rTMS combined with rehabilitation. Further studies are needed to clarify its clinical significance.

Neurology International doi: 10.3390/neurolint18110208

Authors: Mohammed M. Al-Salihi Maryam Sabah Al-Jebur Ahmad Abuaisheh Adam Rizvi Ahmed Saleh Farhan Siddiq Ali Ayyad Adnan I. Qureshi

Background: Successful endovascular thrombectomy does not always result in optimal neurological recovery in patients with acute ischemic stroke, likely because macrovascular recanalization may not fully restore distal or microvascular perfusion. Adjunctive intra-arterial thrombolysis (IAT) has emerged as a potential strategy to enhance reperfusion after thrombectomy, but its efficacy and safety remain uncertain. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing adjunctive intra-arterial thrombolysis after successful endovascular reperfusion versus standard care or placebo in acute ischemic stroke. We searched PubMed, Scopus, Web of Science, and Embase from inception to August 2026. Meta-analysis was performed using Review Manager (RevMan 5.4). Outcomes included excellent functional outcome (modified Rankin Scale [mRS] 0–1), functional independence (mRS 0–2), mortality, Barthel Index, EuroQol five-dimension (EQ-5D) scores, intracranial hemorrhage (ICH), symptomatic ICH, and systemic bleeding. Subgroup analyses were conducted according to thrombolytic agent and circulation territory. Exploratory trial sequential analysis (TSA) assessed the accumulating evidence for selected outcomes under specified assumptions. Results: Nine trials contributed data on 2810 patients. Adjunctive intra-arterial thrombolysis increased the likelihood of excellent functional outcome at 90 days compared with control (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.13–1.35; p < 0.00001), with low statistical heterogeneity (I2 = 17%). TSA supported this finding under the specified assumptions, with the required information size of 1321 patients exceeded. Functional independence did not differ significantly (RR 1.03, 95% CI 0.96–1.10); its TSA remained inconclusive, with 2805 patients representing 8.2% of the required information size of 34,407. Mortality (RR 1.05, 95% CI 0.90–1.23), symptomatic ICH (RR 1.19, 95% CI 0.83–1.71), and systemic bleeding did not differ significantly; these findings do not exclude clinically important harm. Any ICH was more frequent with IAT (RR 1.17, 95% CI 1.03–1.32; p = 0.02), but TSA was inconclusive. EQ-5D scores did not differ significantly. Subgroup findings were exploratory. Conclusions: Adjunctive IAT after successful thrombectomy was associated with a higher likelihood of excellent functional recovery at 90 days. TSA supported this benefit under the stated assumptions but did not establish that future evidence cannot change the estimate. IAT was associated with a modest increase in any ICH that was not confirmed by TSA. Evidence for functional independence and symptomatic hemorrhage remains inconclusive, and nonsignificant safety comparisons should not be interpreted as equivalence. Further trials should evaluate efficacy, patient selection, agent and dose, circulation territory, and adequately powered safety outcomes.

Neurology International doi: 10.3390/neurolint18110207

Authors: Anh T. Tran Liliane Ryan Gaby Abou Karam Dorin Zeevi Ajay Malhotra David Roh Santosh B. Murthy Guido J. Falcone Kevin N. Sheth Seyedmehdi Payabvash

Background: Early neurological deterioration (END) after intracerebral hemorrhage (ICH) is associated with poor prognosis, but its independent contribution to mortality and disability beyond baseline severity remains undetermined. Using causal inference methods, we estimated the effect of END on 3-month outcomes and the population-level impact of preventing END. Methods: Consecutive patients with acute ICH presenting within 12 h of symptom onset at a comprehensive stroke center (2014–2023) were retrospectively analyzed. END was defined as a ≥4-point increase in National Institutes of Health Stroke Scale (NIHSS) score or a ≥2-point decrease in Glasgow Coma Scale (GCS) score within 24 h. Multivariable logistic regression identified baseline predictors of END. The average treatment effect (ATE) of END on the 3-month mortality rate and poor functional outcome rate (mRS of 4–6) was estimated using G-computation, inverse probability weighting, and targeted maximum likelihood estimation (TMLE; primary), adjusting for baseline severity and clinical confounders. TMLE-based counterfactual analyses estimated the population-level impact of preventing END. Results: Among 690 patients (median age of 71 [interquartile: 60–81] years; 308 (44.6%) female), 273 (39.6%) developed END. Across the estimators, END increased the absolute risk of 3-month mortality by 23.1–23.9% and poor functional outcomes by 20.2–22.8%, with no significant effect on disability among the survivors. Counterfactual analyses projected that preventing END would reduce the mortality rate from 31.6% to 21.3% (population attributable fraction of 32.5%) and poor functional outcomes from 56.8% to 48.8% (population attributable fraction of 14.2%). Conclusions: In this single-center cohort, END was associated with a substantially higher 3-month mortality rate and poor functional outcomes, independent of measured baseline severity and other clinical confounders. If this is causal, then END is a potential target for early intervention and a candidate early efficacy endpoint for ICH trials; whether preventing END improves outcomes requires prospective evaluation.

Neurology International doi: 10.3390/neurolint18110206

Authors: Rizaldy Taslim Pinzon Immanuel Usodo Stefanus Erdana Putra

Background: Spinal gout is an uncommon manifestation of chronic hyperuricemia caused by the deposition of monosodium urate (MSU) crystals within axial skeletal structures. Although gout predominantly involves peripheral joints, axial deposition within the ligamentum flavum, facet joints, and epidural space can lead to spinal cord compression and severe neurological impairment. Because clinical and radiological features mimic spinal neoplasms, epidural abscesses, and degenerative disorders, diagnostic delays are common. Case Presentation: A 58-year-old man with an 8-year history of poorly controlled hyperuricemia and essential hypertension presented with progressive lower-limb weakness, severe thoracic back pain, lower-body numbness below the T10 dermatome, and acute urinary retention over two weeks. Neurological examination revealed flaccid paraplegia (Medical Research Council grade 0/5 in both lower extremities), complete loss of pinprick and light touch sensation below T10, absent deep tendon reflexes, and loss of anal sphincter tone, corresponding to American Spinal Injury Association (ASIA) Impairment Scale Grade A. Serum uric acid was elevated at 9.5 mg/dL, alongside mildly elevated inflammatory markers. Magnetic resonance imaging (MRI) revealed a posterior extradural mass from T9 to T12 with severe cord compression centered at the T11–T12 level. Multi-sequence MRI demonstrated T1 iso/hypointensity, T2 heterogeneous hypointensity, thick peripheral rim enhancement on post-contrast T1-weighted sequences, and no restricted diffusion on DWI. Emergency decompressive laminectomy was performed, revealing a chalky white mass compressing the dural sac. Histopathological evaluation confirmed monosodium urate crystal deposits surrounded by granulomatous inflammation and multinucleated foreign-body giant cells. Postoperatively, the patient was initiated on treat-to-target urate-lowering therapy with allopurinol alongside short-term colchicine prophylaxis. At the 6-month follow-up, lower-limb motor strength recovered to grade 4/5, cutaneous sensation was restored, voluntary sphincter control was regained (ASIA Impairment Scale Grade D), and serum uric acid was normalized to 5.2 mg/dL. Conclusions: Spinal gout should be considered in the differential diagnosis of acute spinal cord compression, even in patients without active peripheral tophi. Prompt surgical decompression combined with long-term urate-lowering therapy is essential to facilitate neurological recovery and prevent disease recurrence.

Neurology International doi: 10.3390/neurolint18110205

Authors: Taif Mansour Almaqboul Jude Fahad Al Zamil Ahmed Arif Alabbad Hamzah Abdulhamid Hakeem Mteb Saleh Alserhani Aljwharah Soud Alanzi Sultan Alsalmi

Background: Spinal tumors can lead to severe pain, neurological issues and spinal instability. Surgery and radiotherapy are often performed, but protecting the spinal cord during tumor management is still difficult. During surgery, intraoperative brachytherapy delivers radiation directly to the tumor or surgical bed. This review outlines the evidence available regarding its use, outcomes and complications in patients with spinal tumors. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted a systematic literature review in PubMed, ClinicalTrials.gov, the Cochrane Library, Scopus, and Google Scholar for studies published between 2000 and 2025. We included studies evaluating intraoperative brachytherapy for primary or metastatic spinal tumors. The outcomes included overall survival, pain control (Visual Analog Scale), local tumor recurrence, and neurological and functional outcomes. Data were synthesized narratively because substantial clinical and methodological heterogeneity was observed among the included studies. The risk of bias was assessed using the ROBINS-I tool. Results: Seven studies involving 301 patients were included. The studies evaluated different approaches, including permanent iodine-125 seed implantation, plaque-based irradiation, phosphorus-32 brachytherapy, 50-kV intraoperative radiotherapy, and kyphoplasty combined with intraoperative radio-therapy. Individual studies reported local control of 75% at 24 months and 72.9% at 3 years; another study reported 97.1%, 95.9%, and 94.2% at 6, 12, and 24 months, respectively. These are study-specific estimates and were not pooled. In one cohort, local control was reported per treated vertebra, whereas survival was reported per patient. All seven studies had a serious overall risk of bias, and the evidence was limited by small samples, non-randomized designs, and differences in interventions and outcome definitions. Conclusions: IOBT may be a local treatment option for selected patients, but the available evidence does not establish its independent benefit or superiority to contemporary postoperative stereotactic body radiotherapy (SBRT).

Neurology International doi: 10.3390/neurolint18110204

Authors: Atef F. Hulliel Asem A. Almomani Rawhi Alshaykh Adam M. Abdallah Bayan Maraqa Mouness Obeidat

Background: Intra-axial brain schwannomas are exceptionally rare, accounting for less than 1% of all intracranial schwannomas. Their rarity and non-specific radiological features make diagnosis and management challenging. This study provides a systematic review of the existing literature to summarize the clinical, radiological, histopathological, surgical, and outcome characteristics of reported cases. Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search of PubMed and Scopus was performed using predefined keywords. Studies reporting intra-axial brain schwannomas were included. Data were extracted on patient demographics, clinical presentation, radiological features, tumor location, surgical management, histopathological findings, and outcomes. In total, 80 studies comprising 131 patients were included. Results: The pooled analysis showed that intra-axial schwannomas most commonly occur in young adults, with a median age of 23 years. The most frequent presenting symptoms were seizures, headache, and focal neurological deficits. Radiologically, lesions typically demonstrated heterogeneous contrast enhancement with frequent cystic degeneration. The frontal and temporal lobes were the most commonly affected sites. Surgical resection, most often via craniotomy with gross total resection, was the predominant management strategy. Overall, most reported cases demonstrated favorable postoperative outcomes. Conclusions: Intra-axial brain schwannomas are rare entities that should be considered in the differential diagnosis of intra-axial brain tumors. Surgical resection remains the mainstay of treatment and is generally associated with excellent outcomes.

Neurology International doi: 10.3390/neurolint18110203

Authors: Rumesh Nelumdeniya Sriaandhal Sabalingam Nimantha Karunathilaka Ranga S. Jayakody

Background: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Multiple sclerosis (MS) collectively affect millions of people worldwide, and substantial unmet needs remain for therapies that preserve neuronal structure and function. Current treatments can alleviate symptoms or modify selected disease processes, but they do not comprehensively target the interconnected cellular mechanisms that drive neuronal and axonal injury. Natural, semisynthetic, and synthetic cannabinoids have shown neuroprotective activity in preclinical models, but most remain at an early experimental stage, and their mechanisms of action have not been systematically mapped across disease contexts. Objective: This scoping review maps preclinical evidence, predominantly in vitro, with select studies incorporating in vivo validation, on exogenous cannabinoids and their neuroprotective mechanisms across cellular models of AD, PD, HD, and MS. The compounds examined include phytocannabinoids, synthetic cannabinoid receptor agonists, and cannabinoid-active phytochemicals (e.g., β-amyrin, as described by the original study authors). Methods: This review followed JBI methodological guidance and PRISMA-ScR reporting standards. The protocol was prospectively registered on the Open Science Framework (OSF; 10.17605/OSF.IO/TAQ9F). PubMed, MEDLINE, CINAHL, PsycINFO, and Web of Science were searched, yielding 8484 records (2844 after deduplication). Following two-stage screening in Rayyan, 194 reports were sought for full-text retrieval; 176 were assessed for eligibility, and 26 preclinical studies (2015–2025) met the inclusion criteria. Results: Most included studies were exclusively in vitro (n = 17); six combined in vitro and in vivo methods, and three combined in vitro methods with in silico or ex vivo components. The studies addressed AD (n = 11), PD (n = 8), general neuroinflammation models (n = 5), HD (n = 1), and MS (n = 1). Cannabidiol (CBD) was the most frequently studied compound (n = 9), followed by the synthetic agonists JWH-133 and ACEA (n = 6 combined), THC and its analogs (n = 5), and WIN 55,212-2 (n = 4). Evidence converged on three mechanistic domains: (1) anti-neuroinflammatory signaling in microglia and astrocytes; (2) antioxidant, anti-apoptotic, and mitochondrial pathways; and (3) protein aggregate clearance, autophagy, myelination, and neurotransmitter modulation. Receptor pharmacology emerged as a cross-cutting axis linking these domains, rather than a fourth, parallel mechanism. It spanned canonical cannabinoid receptor type 1 and type 2 (CB1R/CB2R) signaling, non-canonical receptors (peroxisome proliferator-activated receptor γ (PPARγ), G protein-coupled receptor 55 (GPR55), adenosine A2A receptor [A2AR], and transient receptor potential vanilloid 1 (TRPV1)), and receptor heteromerization. Conclusions: Cannabinoid-mediated neuroprotection in AD, PD, HD and MS cannot be explained by canonical receptor pharmacology alone. Three of 26 studies also reported receptor-independent or off-target mechanisms and formulation-dependent effects, highlighting potentially important but under-investigated contributors to cannabinoid-mediated neuroprotection. Translation priorities include systematic dose-response characterization, development of central nervous system (CNS)-penetrant CB2R agonists, and target-deconvolution studies to establish the prevalence of receptor-independent mechanisms and direct molecular effects.

Neurology International doi: 10.3390/neurolint18110202

Authors: Natália de Carvalho Borges Lilian Varanda Pereira José Miguel de Deus Layz Alves Ferreira Souza Louise Amália de Moura

Background/objectives: Cesarean delivery is common, and chronic postsurgical pain (CPSP) may persist, with limited evidence on associated factors and daily-life impact. This study aimed to identify factors associated with CPSP over 48 months of follow-up after cesarean section, to examine whether their associations changed over time, and to assess the impact of CPSP on women’s daily activities. Methods: This was a prospective cohort of 621 women undergoing cesarean section. Participants were assessed preoperatively and followed up at 7 days and 3, 6, 12, 24, 36, and 48 months. Intense acute pain at 7 days (numeric rating scale [NRS] ≥ 7) was assessed as a potential factor associated with CPSP, and CPSP was assessed at each follow-up from 3 to 48 months. Factors associated with CPSP were analyzed using GEE with binomial-logit models, a QIC-selected independent correlation structure, and robust standard errors. Sensitivity analyses addressed missing data, follow-up termination, and the 48-month assessment. Results: The cumulative incidence of CPSP was 25.5% at 3 months, and its prevalence was 5.7% (95% CI: 4.0–8.1) at 48 months. Across the 48 months, factors associated with CPSP included higher preoperative trait anxiety (adjusted OR = 1.06 per point; p = 0.002) and intense pain during the 7-day postoperative period (adjusted OR = 2.28; p < 0.001). These associations did not change over time and were similar in direction in sensitivity analyses. Conclusions: CPSP may persist for years after cesarean section and interfere with women’s activities. Trait anxiety and intense acute postoperative pain were associated with CPSP across the 48-month follow-up.

Neurology International doi: 10.3390/neurolint18110201

Authors: Alejandra Silva Güiza Fernan Alexis Casas Osorio Leonardo Juan Ramirez Lopez

Background: Electroencephalographic (EEG) microstates are transient topographic configurations that index large-scale network dynamics at the millisecond scale. Although widely studied clinically, their characterization in healthy subjects remains fragmentary, hindering the separation of normative from pathological dynamics. Methods: Following PRISMA 2020, we searched PubMed, Scopus, Springer, Web of Science and Google Scholar for studies published between June 2019 and June 2025 (PROSPERO CRD420251106374). Of 5052 records, 91 studies were included; risk of bias was assessed with ROBINS-I. Duration, frequency, coverage, topography and transition probabilities were extracted for classes A–F, and the contributing evidence was characterized by clustering solution size (K = 4 vs. K ≥ 5). Results: Microstates D and C showed the longest mean durations (78.14 and 77.04 ms), A and B intermediate values (69.24 and 66.51 ms) and E and F the shortest (59.93 and 58.75 ms); E and F were supported exclusively by solutions with K ≥ 5. The highest transition probabilities (B ↔ F, E → C) rested on only 4–5 studies, whereas the best-evidenced routes were B → A, B → C, B → D and C → D. Conclusions: These findings are a first step toward a normative reference for healthy adults, contingent on standardizing clustering, filtering and transition metrics.

Neurology International doi: 10.3390/neurolint18110200

Authors: Wenmin Zhu Jinjin Guo Yidi Wang Furong Wang

Background: Cerebral artery dissection is a major cause of stroke in young and middle-aged adults. However, the prevalence of anxiety and depression among patients with cerebral artery dissection, their potential associations with cerebral artery dissection, and the underlying biological mechanisms remain poorly understood. This study aimed to describe anxiety and depression in patients with cerebral artery dissection and to explore potential bidirectional associations and candidate biological processes. Methods: Clinical prevalence and subgroup differences of anxiety and depression in cerebral artery dissection patients were assessed using clinical data. Mendelian randomization (MR) analyses were conducted to evaluate associations between anxiety, depression and cerebral artery dissection. Peripheral-blood RNA sequencing identified cerebral artery dissection-associated differentially expressed genes, which were integrated with anxiety-related genes from GeneCards for enrichment analysis of candidate shared biological processes. Results: Among 726 cerebral artery dissection patients, 315 (43.4%) had anxiety symptoms and 303 (41.7%) had depressive symptoms, with higher proportions in males, ever-smokers, and ever-drinkers. MR analyses provided preliminary evidence of a potential bidirectional association between anxiety and cerebral artery dissection, whereas no consistent evidence of an association was observed between depression and cerebral artery dissection. Integration of cerebral artery dissection-associated differentially expressed genes and anxiety-related genes identified 33 overlapping genes enriched in mitochondrial energy metabolism-related pathways, suggesting candidate systemic transcriptional signatures shared by anxiety and cerebral artery dissection. Conclusions: Anxiety and depression symptoms were frequently observed among patients with cerebral artery dissection. Genetic and transcriptomic analyses suggested potential links between anxiety and cerebral artery dissection, involving candidate mitochondrial energy metabolism-related processes that warrant validation.

Neurology International doi: 10.3390/neurolint18110199

Authors: Lisa B. E. Shields Vasudeva G. Iyer Theresa Kluthe Smita Ghare Christopher B. Shields

Background/Objectives: Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy and is usually associated with classic sensory and motor findings. In rare cases, atypical presentations of CTS may occur, such as pruritus, Raynaud’s phenomenon (RP), and digital ulceration. Our objective is to describe the clinical and electrodiagnostic (EDX) features of patients with CTS who exhibited these uncommon presentations. Methods: This is a review of patients referred for EDX confirmation of CTS, who also had unusual features such as pruritus, RP, and/or digital ulceration over a 12½ year period (1 January 2013–31 July 2026). All patients underwent detailed clinical examination and EDX studies. Results: A total of 106 patients had evidence of CTS with uncommon features: pruritus in 92 (86.8%), RP in 8 (7.5%), digital ulceration in 4 (3.8%), and a combination of pruritus and RP in 1 (0.94%) and digital ulceration and RP in 1 (0.94%). Pruritus was associated with CTS in a total of 137 hands (48 patients unilateral and 45 patients bilateral). Of the 137 hands, the most common location of the pruritus was the palm in 72 (52.6%). A total of 132 (96.4%) of those patients had decreased pinprick sensation, and 21 (15.3%) had weakness and/or wasting of thenar muscles. CTS was graded as moderately severe in 67 (48.9%) of the 137 hands with pruritus. RP was associated with CTS in a total of 16 hands (4 patients unilateral and 6 patients bilateral). All 16 (100%) patients with RP had decreased pinprick sensation, and 3 (18.8%) patients had weakness and/or wasting of the thenar muscles. The CTS associated with RP was mild in 7 (43.8%) patients and moderate in 5 (31.2%). Ulcerative CTS was observed in a total of 7 hands (3 patients unilateral and 2 patients bilateral). All 7 patients with ulcerative CTS had either loss of sensation or hypoesthesia as well as weakness and/or wasting of the thenar muscles. The CTS was severe in all 7 of these patients. The severity of CTS varied by the type of CTS (pruritus, RP, and digital ulceration) (p-value < 0.001). Patients with digital ulceration had more severe symptoms than those with other presentations of CTS (p-value < 0.001). Patients with RP more frequently had mild symptoms compared to those with other presentations of CTS (p-value = 0.01). Conclusions: It is important for physicians of different specialties to be aware of rare, atypical clinical presentations of patients with CTS. These presentations include pruritus, RP limited to median nerve-innervated digits, and digital ulceration. These patients should be promptly referred for EDX studies to confirm the diagnosis of CTS.

Neurology International doi: 10.3390/neurolint18100198

Authors: Dimitar Taskov Sonya Ivanova Izabel Antova Nikolay Topalov Alexandra Barkalova-Atanasova Nikolay Y. Yordanov Ivan Milanov

Background: Sleep disturbance is common in multiple sclerosis (MS), but its relationship with relapse status remains insufficiently defined. This study examined whether poorer subjective sleep quality was associated with relapse status in patients with relapsing-remitting multiple sclerosis. Methods: This propensity score–matched nested case–control analysis included 132 patients with relapsing-remitting MS selected from 473 consecutively evaluated patients at a tertiary multiple sclerosis centre. Patients in relapse were matched 1:1 to patients in remission by age, sex, disease duration, Expanded Disability Status Scale score, disease-modifying therapy duration and efficacy class, and relapse in the previous year. Sleep quality and related symptoms were assessed using validated questionnaires. Results: Patients in relapse were more frequently classified as poor sleepers than those in remission (59.1% vs. 36.4%; p = 0.009). In the double-adjusted logistic regression model, higher Pittsburgh Sleep Quality Index scores were independently associated with relapse status (OR = 1.16; 95% CI 1.02–1.32; p = 0.023), whereas the remaining variables were not independently associated with relapse status. Conclusions: Poorer subjective sleep quality was independently associated with relapse status in relapsing-remitting MS, supporting sleep disturbance as a relapse-associated clinical feature rather than a proven causal risk factor.

Neurology International doi: 10.3390/neurolint18100197

Authors: Assel Meiramova Bayan Ainabekova Yernar Tursynbet Zhanar Akhmetova

Background/Objectives: Prolonged and persistent migraine aura may mimic cerebral ischemia, but its clinical course and neuroimaging features are poorly characterized. We synthesized episode-level evidence on non-motor aura lasting more than 60 min without reported established infarction. Methods: This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] CRD420261461238) followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Scopus, and Google Scholar were searched from inception to August 2026 and the searches were rerun with an extended strategy on 5 October 2026, supplemented by backward and forward citation searching. Eligible reports provided individual-episode clinical data and temporally related neuroimaging. Owing to publication selection, heterogeneous reporting, and clustering, the synthesis was descriptive. Results: Forty-eight studies described 80 episodes in 79 individuals (49 prolonged; 31 persistent). Visual aura occurred in 63/80 episodes. Although magnetic resonance imaging was performed in 77/80 episodes, patient-level informative diffusion imaging was available in only 28/80 and imaging-based perfusion data in 28/80. Five of the 28 episodes with informative diffusion imaging were diffusion-positive (17.9%); the acute apparent diffusion coefficient (ADC) was reduced in 3, non-restricted in 1, and unreported in 1, and all diffusion-weighted imaging (DWI) abnormalities resolved on follow-up. Unusual imaging findings are more likely to be published; this proportion is therefore hypothesis-generating rather than a frequency estimate. In the longer-follow-up stratum, aura improvement was reported in 36/36 prolonged and 18/22 persistent episodes, with complete resolution in 35/35 and 15/22, respectively; a nerve-block series with a fixed 24-h assessment (14 episodes) was analyzed separately. Conclusions: Published cases show heterogeneous phenotypes and cannot support estimates of prognosis or treatment effectiveness. Standardized prospective data collection should incorporate symptom-level duration, imaging timing, DWI/ADC reporting, treatment timing, and protocol-defined follow-up.

Neurology International doi: 10.3390/neurolint18100196

Authors: Maria-Gabriela Vladoiu Madalina Valeanu

Background: Thyroid dysfunction is a relatively common condition; however, the clinical relevance and long-term effects of subclinical thyroid dysfunction on cardiovascular and cerebrovascular morbidity remain uncertain. This study evaluated the association between subclinical thyroid dysfunction and cerebrovascular disease, focusing on lipid metabolism, carotid atherosclerosis, and stroke severity. Methods: This study included 80 adult patients consecutively admitted with acute ischemic stroke who were newly diagnosed with subclinical thyroid dysfunction. Patients were evaluated over a three-year period (2020–2022). Clinical data, extracranial carotid Doppler ultrasonography, and laboratory parameters (including TSH, FT4, and total cholesterol) were analyzed to establish correlations with stroke characteristics. Results: Subclinical hypothyroidism was identified in 83.75% of patients, while subclinical hyperthyroidism was present in 16.25%. A strong positive linear correlation was observed between serum TSH and total cholesterol levels (r = 0.794, p < 0.001). TSH levels significantly correlated with both the severity of carotid artery stenosis and the National Institutes of Health Stroke Scale (NIHSS) score in patients with anterior circulation stroke. Subclinical hyperthyroidism was identified as a protective factor against moderate or severe carotid atheromatosis (OR = 0.211, p = 0.038); however, 78% of these patients presented with newly diagnosed atrial fibrillation. Conclusions: Subclinical thyroid dysfunction is significantly associated with cerebrovascular pathology through distinct mechanisms. Subclinical hypothyroidism contributes to atherosclerotic vascular disease and greater stroke severity, whereas subclinical hyperthyroidism predisposes predominantly to arrhythmia-mediated embolic events.

Neurology International doi: 10.3390/neurolint18100195

Authors: Nino Shatirishvili

Chronic traumatic encephalopathy (CTE) is a progressive tauopathy associated with repetitive head impacts (RHIs) and is currently confirmed only at autopsy. The absence of a validated antemortem diagnostic limits individual risk assessment, clinical trial enrollment, and differentiation from disorders such as Alzheimer’s disease (AD). This review critically evaluates five candidate fluid biomarkers: phosphorylated tau (p-tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and soluble TREM2 (sTREM2). For each, the review assesses the biological mechanism, CTE/RHI-specific evidence, diagnostic performance, and major confounders. None currently provides CTE-specific discrimination. In the largest cohort, plasma p-tau217 tracked amyloid status rather than CTE pathology. NfL reflects axonal injury but is nonspecific and strongly age-dependent. GFAP is associated with clinical CTE certainty in football and combat-sport cohorts, although not in an independent rugby cohort. S100B responds acutely to head impacts without a persistent cumulative signal. sTREM2 may reflect microglial activation that is bidirectionally related to tau after RHI exposure, but its primary case–control comparison was null. Short study windows may also be poorly matched to CTE’s multi-decade latency, and most evidence for p-tau, NfL and GFAP derives from one cohort, with the total tau, extracellular-vesicle and sTREM2 findings from a second. The review therefore emphasizes multi-marker panels, assay standardization, and longitudinal antemortem-to-autopsy cohorts as the validation work required before any fluid biomarker can support antemortem CTE detection.

Neurology International doi: 10.3390/neurolint18100193

Authors: Maciej Giecko Filip Bossowski Magdalena Bossowska Anna Moniuszko-Malinowska Monika Chorąży Magdalena Sarnowska Sambor Grygorczuk

Background/Objectives: Neurosyphilis is a recognized treatable mimic of amyotrophic lateral sclerosis (ALS); syphilis serology is commonly included in the work-up of suspected motor neuron disease. We describe the converse situation: neurosyphilis that delayed recognition of coexisting ALS. Methods: A 46-year-old man with type 2 diabetes mellitus and degenerative spine disease presented with a six-month history of progressive limb weakness and gait disturbance. Serum syphilis serology was reactive (Venereal Disease Research Laboratory [VDRL] titer 1:32; Treponema pallidum hemagglutination assay [TPHA] titer 1:20,480), and cerebrospinal fluid (CSF) showed a mild mononuclear pleocytosis with raised protein and immunoglobulin G. Neurosyphilis was diagnosed and treated with a 14-day course of intravenous penicillin. The subsequent course was followed with neuroimaging and electrodiagnostic studies. Results: Despite treatment and resolution of the CSF pleocytosis, weakness and wasting progressed and bulbar involvement developed. Examination showed combined upper and lower motor neuron signs, electromyography showed an anterior horn cell pattern with widespread fasciculations, and cervical spine imaging showed degenerative changes without spinal cord compression. ALS was diagnosed at a later neurological admission. Conclusions: Identifying a treatable mimic does not close the diagnostic process. Combined upper and lower motor neuron signs that continue to progress despite adequate treatment of neurosyphilis should prompt early electrodiagnostic evaluation for ALS, even though the relative contribution of each condition may remain uncertain.

Neurology International doi: 10.3390/neurolint18100194

Authors: Sorina Nicoleta Munteanu Dana Tutunaru Aurel Nechita Mihai Cristian Marinescu Claudiu Elisei Tanase Ioana Navalici Dorel Firescu Mihaela Moisei Adrian Stan Aurelia Romila

Background/Objectives: This study describes symptomatic intracranial hemorrhage (sICH) after intravenous alteplase in older adults with acute ischemic stroke. Methods: This retrospective single-center cohort included 95 unique patients aged ≥65 years treated in Galati, Romania, in 2020–2024. The binary hemorrhage variable was verified against clinical and computed tomography (CT) records. Study-defined sICH required new or increased CT hemorrhage with attributed deterioration, comprising a ≥4-point National Institutes of Health Stroke Scale (NIHSS) increase or other clinically relevant worsening. Comparisons and Firth models were exploratory, with admission NIHSS adjustment. Results: All 14 recorded hemorrhages met this definition (14.7%; 95% CI 9.0–23.2%): 10 met the NIHSS threshold and four had relevant worsening below it. Ten were detected before 24 h and four at the 24–48 h range; morphology included hemorrhagic infarction and parenchymal hematoma. All adjusted intervals included the null. Median hospitalization was five days longer with sICH. The mortality difference was 2.6 percentage points (conservative exact 95% CI range from −31.6 to 45.9). Conclusions: Adjusted association estimates are inconclusive and do not justify altering guideline-based eligibility. Prospective multicenter studies require standardized definitions, stroke-severity measures, reperfusion data, and functional outcomes.

Neurology International doi: 10.3390/neurolint18100192

Authors: Dilek Baykal Ozge Fircasiguzel Demet Aygun

Background: Stroke in young adults is an increasingly important public health concern because of its long-term impact on cognitive functioning, psychological well-being, and social participation. Understanding the interplay between cognitive impairment, psychological distress, and stroke severity is essential for optimizing post-stroke management. Objective: To compare cognitive function and symptoms of depression, anxiety, and stress between young adults with stroke and healthy controls and to investigate the associations of these outcomes with sociodemographic and disease-related characteristics. Methods: This cross-sectional case–control study was conducted at a university hospital in Türkiye between January and December 2025. A total of 160 participants, including 80 patients aged 18–<65 years with a clinical diagnosis of stroke and 80 healthy controls, were enrolled. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE), neurological severity using the National Institutes of Health Stroke Scale (NIHSS), functional disability using the Modified Rankin Scale (mRS), and psychological symptoms using the Depression Anxiety Stress Scale-21 (DASS-21). Group differences were examined using multivariate general linear models, and Pearson correlation analyses were performed to evaluate associations between disease-specific characteristics and psychological and cognitive outcomes. Results: Across the study groups, the control group exhibited significantly higher levels of depression, anxiety, and stress than the stroke group. These between-group differences remained significant after adjustment for age, whereas the age-adjusted between-group difference in MMSE scores was not statistically significant. Age was not significantly associated with depression, anxiety, or stress scores but was significantly associated with MMSE performance. After adjustment for study group and age, the examined sociodemographic characteristics—gender, education level, employment status, income level, marital status, alcohol use, and smoking—showed no statistically significant main effects on depression, anxiety, stress, or MMSE scores. Although employment status showed a trend toward an association with anxiety, this finding did not reach statistical significance (p = 0.053). Higher NIHSS and mRS scores were significantly associated with higher depression, anxiety, and stress scores and lower MMSE scores (all p < 0.001). Conclusions: Psychological distress and cognitive performance demonstrated distinct patterns of association in young adults following stroke. Neurological severity and functional disability were consistently associated with both psychological distress and cognitive performance. After adjustment for study group and age, the examined sociodemographic characteristics showed no statistically significant main effects on depression, anxiety, stress, or MMSE scores. In contrast, age was significantly associated with MMSE performance but not with depression, anxiety, or stress. The unexpectedly higher levels of depression, anxiety, and stress observed among controls persisted after adjustment for age and warrant further investigation, particularly in relation to potential contextual, psychosocial, and recruitment-related factors. These findings highlight the importance of considering psychological, cognitive, neurological, and functional measures together when assessing young adults with stroke.

Neurology International doi: 10.3390/neurolint18100191

Authors: Junhu Liu Bing Zhu Miao Yu Shichao Du

Background: Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder where early diagnosis at the mild cognitive impairment (MCI) stage is critical for timely intervention. While structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) provide complementary pathological information, clinical translation is limited by high feature heterogeneity and the heavy computational burden of 3D deep learning networks. This study aims to propose a lightweight, hybrid multimodal fusion model to overcome these limitations and improve diagnostic efficiency. Methods: A lightweight MobileViT-XS network was utilized to extract global and local pathological features from gray-matter sMRI images to reduce computational costs. Concurrently, graph theory was applied to rs-fMRI data to construct brain functional networks and calculate global topological properties. Following pretraining, feature-level fusion was performed to integrate sMRI features, rs-fMRI properties, demographic information, and two clinical neuropsychological examinations. Results: The validation results show that the proposed hybrid model achieved high diagnostic performance in the three-class classification task, yielding an accuracy of 0.928 ± 0.010, sensitivity of 0.901 ± 0.014, precision of 0.933 ± 0.014, and an F1 score of 0.911 ± 0.012. On the held-out testing subset of the independently collected dataset after dataset-specific fine-tuning, the proposed model achieved an accuracy of 0.857, with a sensitivity of 0.867, a precision of 0.867, and an F1 score of 0.859. Conclusions: The proposed framework successfully minimizes computational overhead while maintaining high classification accuracy. These findings suggest that the hybrid multimodal fusion model provides a promising computer-aided approach for three-class classification of AD, MCI, and NC.

Neurology International doi: 10.3390/neurolint18100190

Authors: Sladjana M Vasilić-Brasnjević Miloš Z Maksimović Hristina D Vlajinac Andja Ćirković Tijana Dimkić Tomić Branko D Jakovljević Sindi Z Mitrović Suzana Dedijer Dujović Aleksandra S Vidaković

Background/Objectives: This study investigated the association between pre-stroke physical activity (PA) assessed using the Baecke Physical Activity Questionnaire (BPAQ) and functional status after a first-ever ischemic stroke (IS). Methods: This prospective cohort study included 91 patients who had had their first-ever IS and were admitted for inpatient rehabilitation. Functional status was assessed using the Barthel Index (BI) at rehabilitation admission, discharge, and three months after discharge. Linear mixed-effects models (LMMs) were adjusted for age, sex, the National Institutes of Health Stroke Scale (NIHSS) score, and the number of comorbidities. Predictors of BI ≥ 91 were examined using multivariable logistic regression. Results: BI improved significantly over follow-up (p < 0.001). Pre-stroke PA was associated with BI in the adjusted LMM (p = 0.021), whereas the time-by-BPAQ interaction was not significant (p = 0.952). Initial BI was associated with subsequent BI scores (p < 0.001). The work and leisure-time indices were associated with BI (p = 0.033 and p = 0.030), whereas the Sport Index was not (p = 0.089). None of the domain-by-time interactions were significant. Higher BI at rehabilitation admission was associated with higher odds of BI ≥ 91 at discharge and three months after discharge (OR = 1.11, p < 0.001; OR = 1.05, p = 0.015). Conclusions: Pre-stroke PA assessed using the BPAQ was associated with functional status across the observed time points, but there was no evidence that it was associated with a different longitudinal trajectory of BI recovery.

Neurology International doi: 10.3390/neurolint18100189

Authors: Andrei Florin Păduraru Raluca-Sînziana Zaharia Iuliana Roată Lucian Hritcu Razvan Stefan Boiangiu Alin-Mihnea Lupașcu Mădălina-Maria Popescu-Brezuleanu Carmen-Olguța Brezuleanu

Neurological and psychiatric disorders share several biological mechanisms, including mitochondrial dysfunction, oxidative stress, neuroinflammation, impaired protein homeostasis, and changes in synaptic plasticity. Sirtuins (SIRT) are nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that regulate cellular metabolism, gene expression, mitochondrial function, inflammation, and neuronal survival. This narrative review examines the roles of SIRT1–SIRT7 in neurodegenerative and psychiatric disorders and discusses pharmacological approaches that target sirtuins or related pathways. The review was complemented by a bibliometric analysis of publications indexed in the Web of Science Core Collection. Keyword co-occurrence analysis was used to identify the main themes and emerging research directions in the field. Current evidence suggests that activation of SIRT1 and SIRT3 generally supports mitochondrial function and neuronal resistance to stress, whereas inhibition of SIRT2 may be beneficial in some models of protein aggregation and cerebral ischemia. However, the effects of sirtuins vary according to the isoform, cell type, disease, and stage of disease. Pharmacological modulators were grouped into targeted activators, natural compounds that indirectly support sirtuin signaling, NAD+-boosting agents, synthetic inhibitors, and endogenous inhibitors with context-dependent effects. Among the more selective activators, SRT2104 and MDL-800 appear particularly relevant, while most natural compounds act as indirect pleiotropic modulators of sirtuin-associated signaling, although their translational validation remains limited. Overall, sirtuin modulation is a promising but complex therapeutic approach. Its clinical translation is still limited by poor isoform selectivity, indirect mechanisms of action, dose- and timing-dependent effects, uncertain blood–brain barrier penetration and insufficient clinical validation.

Neurology International doi: 10.3390/neurolint18100188

Authors: Dominika Jakubowicz-Lachowska Mateusz Wierciński Katarzyna Kapica-Topczewska Alina Kułakowska Eugeniusz Tarasow Jan Kochanowicz Monika Chorąży

Introduction: Foix–Alajouanine syndrome (FAS) is a rare, progressive congestive ischaemic myelopathy caused by a spinal dural arteriovenous fistula (SDAVF). Because of its non-specific clinical presentation and subtle imaging features, FAS is frequently misdiagnosed; in particular, perimedullary flow voids—its characteristic imaging hallmark—are readily overlooked on initial MRI, leading to diagnostic delay and potentially harmful interventions. Case Presentation: We report the case of a 66-year-old man who developed progressive myelopathy following revision knee arthroplasty performed under spinal anaesthesia. Initial MRI at another institution demonstrated extensive intramedullary T2 hyperintensity, interpreted as spinal cord infarction, while perimedullary flow voids were present but overlooked. Lumbar puncture and high-dose corticosteroid therapy were followed by marked neurological deterioration. At our centre, re-evaluation of a 3T MRI revealed serpentine perimedullary flow voids, and digital subtraction angiography confirmed an SDAVF at the Th5–Th6 level. Outcome: Transarterial endovascular embolisation with Onyx resulted in neurological stabilisation and partial recovery, with reduced pain and improved bladder control at follow-up. Conclusions: This case highlights the importance of recognising perimedullary flow voids, which may otherwise lead to delayed diagnosis of SDAVF. In patients with unexplained longitudinally extensive myelopathy, particularly when the clinical course is atypical or worsens after lumbar puncture or corticosteroid therapy, the MRI should be carefully reviewed for flow voids and dedicated spinal vascular imaging considered.

Neurology International doi: 10.3390/neurolint18100187

Authors: Sara Monleón Guinot Constanza San Martín Valenzuela Vivina Aranda Asensi José M. Tomás

Background/Objectives: Dual-task (DT) motor assessment in Parkinson’s disease (PD) provides insight into functional abilities, yet limited evidence on its reliability may bias therapy results. This study aims to evaluate the intra-rater test–retest reliability of single and functional DT balance measures in untrained individuals with PD, and to determine the Standard Error of Measurement (SEM) and the Minimal Detectable Change (MDC). Methods: In this cross-sectional study, 22 untrained participants with PD performed a balance assessment twice, 30 min apart. The Romberg test was measured on a force platform under five conditions: single-task, two cognitive secondary tasks (visual, DTvisual; verbal, DTverbal) and two manual tasks (below 90° of shoulder flexion, DTlower; above 90°, DTupper). Test–retest reliability of Center of Pressure (CoP) outcomes was assessed using the Intraclass Correlation Coefficient (ICC) besides SEM and MDC. Results: Displacement, dispersion, force, swept area, and velocity of CoP movements showed excellent reliability (ICC > 0.75) under the single-task condition, except for anteroposterior displacement, which showed an ICC of 0.73. Swept area (ICC = 0.92), followed by CoP velocity (ICC = 0.90) and anteroposterior CoP force (ICC = 0.90), exhibited the highest reliability. Under dual-task conditions, reliability was more variable across outcomes and task types. CoP velocity showed the most consistent reliability (ICC = 0.74–0.92), whereas swept area showed lower reliability in all DT conditions, but DTupper (ICC = 0.90). Mediolateral CoP outcomes were more reliable than anteroposterior displacement and dispersion, while anteroposterior CoP force outperformed mediolateral force under DT conditions. Conclusions: Single-task static balance can be reliably assessed in untrained people with mild-to-moderate PD within a single session. However, under DT conditions, high variability across outcomes warrants cautious interpretation, highlighting CoP velocity and mediolateral excursion as relatively consistent outcomes.

Neurology International doi: 10.3390/neurolint18100186

Authors: Junxiang Xu Yijin Chang Dong Liu Changsheng Chen

INPP5D, which encodes Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1), has emerged as an Alzheimer’s disease (AD)-associated gene with strong links to microglial biology. As a hematopoietic-enriched lipid phosphatase, SHIP1 converts phosphatidylinositol-3,4,5-trisphosphate to phosphatidylinositol-3,4-bisphosphate, thereby regulating phosphoinositide-dependent receptor signaling, membrane remodeling, phagocytosis, vesicle trafficking, and inflammatory responses. In AD, microglia are chronically exposed to amyloid-β, lipid-rich debris, damaged synapses, complement-tagged structures, and inflammatory mediators. These substrates require coordinated uptake, endolysosomal processing, autophagic adaptation, and controlled inflammatory output. Current data place INPP5D/SHIP1 at a step after receptor engagement, where microglial uptake must be coupled to vesicular routing and lysosomal degradation. When this coupling fails, engulfed amyloid, lipid debris, or synaptic material may accumulate in stressed endolysosomal compartments, promoting defective autophagy, NLRP3 inflammasome activation, and sustained cytokine release. Although current data support a primarily microglial or myeloid-centered role for INPP5D in the brain, altered microglial states may secondarily affect the neurovascular unit through cytokine release, complement activation, oxidative stress, and impaired amyloid or lipid clearance. This review summarizes the molecular function of INPP5D/SHIP1 in AD-related microglial signaling and discusses its implications for phagocytosis, endolysosomal stress, inflammasome activation, therapeutic targeting, and microglia–vascular communication.

Neurology International doi: 10.3390/neurolint18100185

Authors: Samirah A. Alameer Reem T. Alturki Alanood F. Alsaleh Meaad M. Almusined

Background: Acute ischemic stroke (AIS) is a major cause of mortality. Despite substantial advances in stroke diagnosis, investigation, and therapeutic management, the need for improved prognostic assessment remains an important clinical challenge. This study aimed to evaluate the role of combining magnetic resonance imaging (MRI)-derived and blood biomarkers in predicting functional outcomes in AIS at 3 months. Methods: A retrospective observational cohort study used data from Prince Mohd bin Naser Hospital in Saudi Arabia to integrate clinical variables and MRI-derived and blood biomarkers from adult patients with AIS. Results: The primary outcome, 3-month functional status, was assessed by the modified Rankin Scale (mRS) (good outcome: mRS < 3; poor outcome: mRS ≥ 3). The corrected analytical cohort included 100 patients. Among the 100 patients (median age: 61 years; male: 75.0%), 67 and 33 had good and poor 3-month outcomes, respectively. Compared with the good outcome group, the poor outcome group had significantly higher National Institutes of Health Stroke Scale (NIHSS) score at admission, which was the strongest discriminator between the two groups, and a trend toward a lower lesion’s mean apparent diffusion coefficient (ADC) that did not reach statistical significance. Multivariable analysis showed the best predictive performance (area under the curve (AUC): 0.934; cross-validated AUC: 0.906) with the base model consisting of admission NIHSS, lesion’s mean ADC, neutrophil percentage, and red cell distribution width; this cross-validated performance was not statistically distinguishable from a comparator model using NIHSS alone (CV-AUC: 0.898). Correlation analyses showed weak-to-moderate relationships between MRI-derived and blood biomarkers, with no correlations remaining significant after false discovery rate correction. Conclusions: Admission NIHSS score was the most powerful and consistent predictor of the 3-month outcome, while the incremental value of the multimarker model over NIHSS alone requires confirmation in larger, externally validated cohorts.

Neurology International doi: 10.3390/neurolint18100184

Authors: Armando Almeida Isaura Tavares

Descending pain modulation is a major determinant of pain processing across physiological and pathological conditions. Although descending pain modulation has long been recognized as bidirectional, capable of both inhibiting and facilitating nociceptive transmission, recent advances now allow it to be examined with far greater anatomical, cellular, neurochemical, and functional precision. Circuit tracing, optogenetic and chemogenetic manipulation, molecular profiling, connectomics, and human neuroimaging have expanded classical brainstem models, revealing a modulatory network in which inhibitory and facilitatory influences are dynamically recruited according to physiological and pathological state. In this narrative review, we revisit descending pain modulation across acute, inflammatory, neuropathic, and nociplastic pain states. We discuss canonical pathways, including the periaqueductal gray–rostral ventromedial medulla axis and locus coeruleus–spinal noradrenergic projections, together with the established dorsal reticular nucleus system and more recently identified descending circuits. We examine how circuit organization, neurochemical diversity, and local and long-range network interactions shape modulatory output across pain conditions. Attention is given to state-dependent plasticity and to the progressive reorganization of descending systems during pain chronification. In this context, reduced inhibitory flexibility and enhanced facilitatory bias emerge as recurrent, but not uniform, features of chronic pain. We also consider how human experimental paradigms, pharmacological approaches, and neuroimaging findings can be interpreted in light of these mechanistic advances, while acknowledging the limits of translating circuit-specific animal findings into integrated human measures. By framing descending pain modulation as a distributed and dynamically reconfigurable network rather than as a unitary analgesic system, this review highlights its relevance to pain phenotyping, treatment stratification, and mechanism-informed therapeutic strategies.

Neurology International doi: 10.3390/neurolint18100183

Authors: Gamaliel Wibowo Soetanto Elvan Wiyarta

Background: Unlike acute basilar artery occlusion, non-acute vertebrobasilar occlusion has limited evidence for intervention and requires individualized risk assessment. Case Presentation: A 62-year-old woman developed progressive vertigo, diplopia, dysarthria, and gait ataxia over ten days. Dual antiplatelet therapy was started after posterior circulation ischemia was suspected, but symptoms continued to progress. MRI showed acute to subacute left cerebellar infarction, and CTA showed absent antegrade basilar opacification with collateral distal filling. DSA showed distal left vertebral artery occlusion, retrograde basilar filling through posterior communicating artery collaterals, and hypoplastic right vertebral artery. Endovascular recanalization was performed after multidisciplinary review and informed consent. Intraluminal crossing, stepwise angioplasty, and stent reconstruction restored antegrade basilar flow without angiographic complications. NIHSS improved from 5 to 2 at discharge, and mRS was 1 at 30 days. No follow-up vascular imaging was available. Conclusions: This case illustrates technical feasibility in selected non-acute vertebrobasilar occlusion, but does not establish medical treatment failure, causal recovery, generalizable safety, or long-term durability.

Neurology International doi: 10.3390/neurolint18100182

Authors: Elpida Stratou Christina Athanasopoulou Aristotelis Koinis Georgia-Nektaria Porfyri Symeon Dimitrios Daskalou Nikolaos Gerosideris Evangelia Arvanitidou Aikaterini Gamvroula George Pierrakos Ioanna Giannoula Katsouri

Background/Objectives: Cognitive impairment is a core feature of schizophrenia and is closely associated with everyday functioning and participation. This study examined the effects of a 12-week occupation-based group occupational therapy intervention on cognitive functioning in adults with schizophrenia. Methods: In this two-arm randomized controlled trial, 86 adults with schizophrenia were randomly allocated to an intervention group (n = 44) or a treatment-as-usual control group (n = 42). The intervention combined cognitive activation with everyday tasks, problem-solving, and social and creative activities. Co-primary outcomes were the Mini-Mental State Examination (MMSE), Addenbrooke’s Cognitive Examination III (ACE-III) total score, and Clock Drawing Test (CDT). Secondary outcomes included the Mini-Addenbrooke’s Cognitive Examination (M-ACE), ACE-III domains, and Trail Making Test (TMT) Parts A and B completion times and error counts, assessed at baseline and post-intervention. Group × time effects were examined using repeated-measures analysis of variance. Results: All 86 participants completed the post-intervention assessment and were included in the analysis. Compared with treatment as usual alone, the intervention was associated with significantly greater improvements in MMSE, ACE-III total, M-ACE, TMT Part A completion time, and the ACE-III language and visuospatial domains. Partial η2 values ranged from 0.17 to 0.43, with the largest effect observed for the ACE-III total score. Conclusions: Adding occupation-based group occupational therapy to usual care may improve global and domain-specific cognitive test performance in adults with schizophrenia. Further research should determine whether these changes are maintained and translate into everyday occupational performance and participation. This trial was retrospectively registered with ISRCTN (ISRCTN43725423).

Neurology International doi: 10.3390/neurolint18100181

Authors: Maia Tighashvili Nina Mikeladze Nazibrola Botchorishvili Ann Dzagnidze Nino Chitauri Tamar Sakvarelidze Marina Janelidze Zurab Nadareishvili

Background: Post-stroke cognitive impairment (PSCI) affects approximately half of stroke survivors within the first year. Data from low- and middle-income countries, including Georgia, are limited. Although a Georgian-language version of the Montreal Cognitive Assessment (MoCA) has previously been validated as a brief cognitive screening instrument, no validated Georgian-language multidomain neuropsychological battery for vascular or post-stroke cognitive impairment is currently available. This study aimed to validate the Georgian version of the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network (NINDS–CSN) neuropsychological battery by assessing its concurrent validity with the Montreal Cognitive Assessment (MoCA), and to evaluate its clinical utility for estimating PSCI prevalence. Methods: Patients with ischemic stroke attending a 6-month follow-up visit were prospectively enrolled. The control group (CG) comprised healthy adults. The Georgian NINDS–CSN 30 min battery was administered. Validity for diagnosing PSCI was assessed using receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) as the primary measure. Results: A total of 175 participants were included (73 stroke patients and 102 healthy controls); 34 of 73 stroke patients (46.6%) met the clinical reference criteria for PSCI. In demographically adjusted analyses (n = 72), the four-test NINDS-CSN composite demonstrated good discrimination for clinically defined PSCI (AUC, 0.821); the optimal threshold of −1.144 yielded 78.8% sensitivity and 82.1% specificity. Incorporation of TMT-A and TMT-B into a six-test composite modestly increased the AUC to 0.861, with an optimal threshold of −1.728, 72.7% sensitivity, and 94.9% specificity. The MoCA demonstrated higher discriminative performance (AUC, 0.978; 95% CI, 0.952–1.000); at the previously validated cutoff of ≤22, sensitivity was 97.0%, and specificity was 79.5%. The MoCA AUC was significantly higher than that of the six-test NINDS-CSN composite (AUC difference, 0.117; 95% CI, 0.031–0.204; p = 0.008). Conclusions: The Georgian NINDS–CSN battery demonstrated good discriminative performance. However, given the superior performance of the Georgian MoCA, it may be preferred for screening PSCI in routine practice, while the NINDS–CSN battery remains suitable for comprehensive cognitive assessment.

Neurology International doi: 10.3390/neurolint18100180

Authors: Kyriaki Papadopoulou Sophia Tsokkou Pavlos Pavlidis Sofia Karachrysafi Vasilis Spyridon Tseriotis Dimitrios Kavvadas Asimoula Kavvada Chrysanthi Sardeli Dimitrios Kouvelas Soultana Meditskou-Efthymiadou Antonia Sioga Theodora Papamitsou

Background/Objectives: Aminoglycoside antibiotics such as amikacin are indispensable for treating severe Gram-negative infections, but their clinical use is limited by a well-documented toxicity profile that has focused overwhelmingly on ototoxicity and nephrotoxicity, leaving their action on the peripheral nervous system comparatively unexplored. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in Alzheimer’s disease, has shown protective effects in peripheral-nerve animal models, raising the question of whether it could limit potential amikacin-induced peripheral neurotoxicity. Methods: Adult male Wistar rats were allocated to three groups: Group A: control, no drug administration; Group B: amikacin 20 mg/kg/day intraperitoneally for 14 days; and Group C: concurrent administration of amikacin 20 mg/kg/day plus memantine 10 mg/kg/day intraperitoneally for 14 days. Branches of the brachial plexus and the sciatic nerve were harvested and processed for transmission electron microscopy (TEM), and axonal, myelin and Schwann-cell ultrastructure were assessed in a blinded manner. Results: Group A showed intact axons, compact myelin sheaths and normal Schwann cells. Group B showed pronounced neurotoxic lesions: degeneration of the myelin sheath (splitting, dilation and folding), axoplasmic collapse with swollen organelles, and Schwann cells of abnormal shape. In Group C, memantine markedly attenuated the nerve fiber damage: most axons were preserved, myelin-sheath abnormalities were mild and focal, and numerous normal Schwann cells and unmyelinated nerve fibers were retained. Conclusions: Amikacin exerts a distinct, previously under-recognized ultrastructural neurotoxicity on peripheral nerves, and concurrent memantine confers substantial neuroprotection, supporting a potential adjunctive role for NMDA-receptor antagonism during aminoglycoside therapy.

Neurology International doi: 10.3390/neurolint18090179

Authors: Aishah Ibrahim Albakr Alia Alokley Feras Alsulaiman Abdulrahman Abdulwahab Mohammad AlWatban Dalal Albakr Feras A. Al-Awad Mustafa Ahmed Alqarni Saud A. Alnaaim Ali Hafiz Alhashim Noman Ishaque Modhi AlKhaldi Azra Zafar Fatimah AlSaihati Saleh Saad Alotaibi Firas Saad Alahmari Norah A. AlKhaldi

Background/Objectives: Cerebral small vessel disease (CSVD) is an established determinant of functional outcome after stroke; however, its influence on the longitudinal course of neuropsychiatric recovery remains incompletely understood. We aimed to investigate the association between MRI-defined CSVD burden and longitudinal depressive symptom trajectories, as well as cognitive, anxiety, and functional outcomes after stroke. Methods: This prospective longitudinal cohort study included consecutive patients with acute ischemic stroke or intracerebral hemorrhage treated at a tertiary comprehensive stroke center between January 2022 and November 2025. CSVD burden was quantified using a validated MRI-based Global CSVD Score and categorized as none-to-mild (0–1) or moderate-to-severe (2–4). Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), anxiety using the Generalized Anxiety Disorder-7 (GAD-7), cognitive function using the Montreal Cognitive Assessment (MoCA), and functional outcome using the modified Rankin Scale (mRS) at baseline and 3, 6, and 9–12 months after stroke. Longitudinal depressive symptom trajectories were evaluated using linear mixed-effects models, and multivariable logistic regression was used to assess associations with incident and persistent post-stroke depression, cognitive impairment, and functional outcome. Results: Of 550 participants enrolled, 480 (87.3%) underwent brain MRI and were included in the MRI-defined CSVD analyses. Moderate-to-severe CSVD burden was associated with a less favorable longitudinal depressive symptom trajectory, reflected by a significant CSVD burden × time interaction (β = 0.68, 95% CI 0.25–1.11; p = 0.002). Moderate-to-severe CSVD burden was also independently associated with poor functional outcome (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.04–2.32; p = 0.030). In contrast, baseline CSVD burden was not independently associated with incident post-stroke depression, persistent post-stroke depression, or global cognitive impairment after multivariable adjustment. Conclusions: Greater MRI-defined CSVD burden was associated with a less favorable longitudinal depressive symptom trajectory and poorer functional recovery after stroke, whereas it was not independently associated with incident or persistent post-stroke depression or global cognitive impairment. These findings suggest that cumulative MRI-defined CSVD burden may provide complementary information regarding longitudinal emotional and functional recovery, although its incremental prognostic value and clinical utility require further validation. Multicenter studies with longer follow-up and quantitative neuroimaging are needed to confirm these associations and determine whether CSVD assessment improves risk stratification and individualized post-stroke monitoring and rehabilitation.

Neurology International doi: 10.3390/neurolint18090178

Authors: Atef F. Hulliel Dana Saleh Ahmad Zayd Alkadri David J. Boughanem Rafal Chociej Daven Mejica Bryan Clampitt Srujan Kopparapu Jay Kumar Patrick Kim Mohsen Rostami Puya Alikhani

Introduction: Lateral lumbar interbody fusion (LLIF) provides effective anterior column reconstruction while avoiding extensive posterior dissection; however, its transpsoas trajectory places the lumbar plexus at risk of neurological complications. The incidence, clinical patterns, and predictors of these events remain incompletely defined because of heterogeneous reporting across studies. Method: We performed a retrospective cohort study of consecutive adult patients undergoing transpsoas LLIF at a tertiary spine centre between 2016 and 2023. Demographic, clinical, and operative variables were collected, and postoperative neurological complications were identified from clinical documentation and imaging when available. Multivariable logistic regression was performed to determine independent predictors of transient motor weakness, acute thigh paraesthesia, and transient paraesthesia. Results: Among 545 patients, 167 (30.6%) experienced at least one neurological complication. The most common events were acute thigh paraesthesia (14.4%) and transient motor weakness (13.2%), whereas hip flexion weakness (2.1%), femoral palsy (1.3%), and psoas haematoma (1.4%) were uncommon. Obesity was independently associated with transient motor weakness (OR 1.77, 95% CI 1.06–2.93; p = 0.028). Younger age independently predicted acute thigh paraesthesia (OR 0.96 per year, 95% CI 0.94–0.99; p = 0.002) and transient paraesthesia (OR 0.97 per year, 95% CI 0.94–1.00; p = 0.049). Multilevel surgery was independently associated with acute thigh paraesthesia (OR 1.67, 95% CI 1.02–2.74; p = 0.043). Conclusions: Neurological complications following LLIF are relatively frequent but are predominantly transient sensory disturbances or temporary motor weakness. Obesity, younger age, and multilevel surgery identify patients with increased risk of specific neurological events. These findings support individualized counselling, careful surgical planning, and continued investigation into anatomical and intraoperative factors underlying LLIF-related neurological morbidity.

Neurology International doi: 10.3390/neurolint18090177

Authors: Zongpai Zhang Jingpu Wu Isabel M. Rios Pulgar Elizabeth H. T. Chang Keyi Chai Puyang Wang Shanshan Jiang Xu Li Kenichi Oishi Gwenn S. Smith Carrie Wagandt Gregory M. Pontone Abhay Moghekar Arnold Bakker Jinyuan Zhou

Objectives: Developing sensitive imaging biomarkers is critical for capturing early brain alterations in Alzheimer’s disease. This exploratory study aimed to evaluate how multiparametric magnetic resonance imaging (MRI) measures, including chemical exchange saturation transfer (CEST) imaging, can detect early cognitive impairment and to compare their diagnostic performance across multiple brain regions. Methods: 18 cognitively normal participants and 18 patients with mild cognitive impairment or mild dementia were recruited to undergo CEST and other MRI sequences. Imaging metrics included CEST measures (amide proton transfer-weighted or APTw, APT#, nuclear Overhauser enhancement or NOE#), alongside conventional measures (T1, T2) and advanced measures (magnetization transfer ratio or MTR, quantitative susceptibility mapping or QSM, apparent diffusion coefficient or ADC). Quantitative analyses were performed in the hippocampus, caudate, putamen, posterior cingulate cortex, and amygdala. Associations between MRI measures and cognition were evaluated using Pearson correlation analysis, and the diagnostic performance of single-parameter and multiparameter models were assessed using logistic regression and receiver operating characteristic analysis. Results: Among all evaluated MRI measures, APTw, APT#, NOE#, MTR, T1, and QSM demonstrated statistically significant group differences (cognitively normal vs. mild cognitive impairment or mild dementia), with medium to very large effect sizes in at least one region. Across all evaluated regions, APT# and NOE# signals were consistently and positively associated with clinical dementia severity (based on the Clinical Dementia Rating), whereas MTR showed consistently negative associations. In contrast, APTw, T1, T2, QSM, and ADC exhibited weaker or more region-dependent associations. Correlations with the Mini-Mental State Examination were generally weaker across MRI measures and regions. Among these, APT# showed the strongest and most consistent associations with clinical severity, and was the best single-parameter classifier in most regions. Conclusions: Multiparametric MRI with CEST imaging shows potential for detecting microstructural and molecular alterations associated with cognitive dysfunction in individuals at risk for early cognitive decline.

Neurology International doi: 10.3390/neurolint18090176

Authors: Jadyellen Rondon Silva Maria Elisa Fonseca Oliveira Lira Kamila Palacios Campos Marcos Jose Jacinto Anderson Oliveira Souza

Background: The ingestion of polyunsaturated fatty acids is vital for brain health, supporting cognitive development and helping to prevent chronic diseases, including neurodegenerative processes. Objective: This study aimed to investigate the effects of corn oil on the biochemical and neurochemical parameters of Drosophila melanogaster expressing human amyloid precursor protein β42 (APP-β42). Methods: The flies were fed a diet supplemented with 37.8 mg/mL of corn oil from the larval stage until adulthood. Results: A diet supplemented with corn oil induced significant changes in biochemical markers, such as a decrease in head cholesterol levels (p < 0.001); decreased catalase activity and hydrogen peroxide levels in the heads (p < 0.0001) and thoracic muscles (p < 0.0001); reduced glutathione levels in the heads (p < 0.0001) and muscles (p < 0.01); and reduced formazan production (p < 0.01) and citrate synthase (CS) activity (p < 0.0001) in the head. However, in thoracic muscle, ingestion of corn oil led to an increase in formazan production (p < 0.01) and no significant change in CS activity. Lactate levels decreased in the heads (p < 0.0001) and thoraces (p < 0.001) after flies were fed corn oil. Finally, ingestion of corn oil resulted in a significant rise in acetylcholinesterase activity in the heads (p < 0.001) and thoracic muscles (p < 0.01). Conclusions: These results suggest that consuming corn oil reduces the oxidative stress typical of an Alzheimer’s disease model by enhancing antioxidant defenses.

Neurology International doi: 10.3390/neurolint18090175

Authors: Penka Petleshkova Nevena Anesteva-Ivanova Maya Krasteva Nikoleta Parahuleva Atanas Ivanov Hristo Ivanov Anna Mihaylova

Background: Neuroblastoma is the most common extracranial solid tumor in infancy and demonstrates marked clinical heterogeneity. To our knowledge, this is one of the very few reported cases of neonatal neuroblastoma associated with genetically confirmed achondroplasia and an additional SDHA variant. Case Presentation: We describe a male neonate with a prenatally detected right-sided suprarenal mass and skeletal abnormalities suggestive of achondroplasia. Postnatal evaluation was consistent with localized neuroblastoma, which was classified as low risk according to the available clinical documentation. Despite the initially favorable clinical risk profile, the tumor showed unexpected progression after initial chemotherapy, requiring treatment intensification and subsequent surgical resection. Next-generation sequencing identified a pathogenic FGFR3 c.1138G>A (p.Gly380Arg) variant confirming achondroplasia and an SDHA c.704T>C (p.Ile235Thr) variant of uncertain significance. At follow-up, the patient remained free of disease recurrence. Conclusions: This case expands the limited evidence on the coexistence of neonatal neuroblastoma and achondroplasia and highlights the potential value of comprehensive genomic testing in patients with atypical clinical behavior. It also demonstrates that an initially favorable clinical risk profile does not invariably predict subsequent disease behavior, emphasizing the importance of integrating clinical, radiological, and molecular findings in individualized patient management.

Neurology International doi: 10.3390/neurolint18090174

Authors: Harun Asoglu Tim Lampmann Saif-Eldin Abedellatif Mohammed Jaber Haitham Alenezi Mohammed Banat Hartmut Vatter Motaz Hamed

Introduction: The routine insertion of a postoperative intracranial drain following surgical evacuation of brain abscesses or subdural empyemas is practiced by some surgeons to facilitate pus evacuation and to enable cavity lavage, but robust evidence for clinical benefit is lacking. This study evaluates whether postoperative drain placement affects reoperation rates, length of hospital stay, and duration of antibiotic therapy. Methods: We performed a retrospective review of consecutive adult patients who underwent surgical drainage or excision of a primary intracranial abscess or empyema at our tertiary center between January 2020 and January 2026. Patients were grouped by whether a postoperative intracranial drain was placed. The primary endpoint was recurrence requiring reoperation. Secondary endpoints included hospital length of stay, total duration of antibiotic therapy, and operative time. Continuous variables were compared with t-tests and categorical variables with Fisher’s exact test; p < 0.05 was considered statistically significant. Results: Eighty procedures were identified, and 36 patients met inclusion criteria for final analysis; eight (22.2%) received a postoperative intracranial drain, and 28 (77.8%) did not. Overall, 13 patients (36.1%) required reoperation for radiological or clinical progression. Reoperation occurred in 50% of patients with a drain and 32.1% without a drain (p = 0.422). Median hospital stay and duration of antibiotic therapy did not differ significantly between groups (median hospital stay 27.1 vs. 23.0 days, p = 0.50; median antibiotic duration 67.3 vs. 51.7 days, p = 0.445). Operative time and infection volume rates were also similar between cohorts. Conclusions: In this single-center retrospective cohort, placement of a postoperative intracranial drain after surgical management of brain abscesses or empyemas was not associated with reduced reoperation rates, shorter hospitalization, or shorter antibiotic treatment. Given the absence of demonstrable clinical benefit and the potential risks related to drain placement, routine insertion of postoperative drains cannot be recommended.

Neurology International doi: 10.3390/neurolint18090173

Authors: Mahika Khurana Seyed Mostafa Razavi Balaganesh Natarajan Eman Elmasry Ahmed Abd Elazim

Upper cervical structural disease can alter vertebral artery biomechanics, although a mechanical contribution cannot be established by anatomical proximity alone. We describe an older woman with seronegative inflammatory arthritis and chronic atlantoaxial abnormality who developed abrupt vertigo, nausea, and inability to walk despite a National Institutes of Health Stroke Scale (NIHSS) score of 0. Computed tomography angiography (CTA) demonstrated left V3 vertebral artery dissection with pseudoaneurysmal dilation at the craniovertebral junction. Magnetic resonance imaging (MRI) showed a dominant acute left posterior inferior cerebellar artery (PICA)-territory infarction. Cervical imaging demonstrated atlantoaxial deformity, pannus-like peri-odontoid tissue, and a C1 arch abnormality adjacent to the affected V3 segment. Echocardiography and inpatient telemetry did not identify an embolic source. Anatomical colocalization of the C1-C2 abnormality and V3 lesion, together with the ipsilateral PICA infarction, suggests a possible mechanical contribution to the dissection, with subsequent artery-to-artery thromboembolism to the cerebellum. Dynamic compression was not demonstrated; spontaneous dissection, intracranial atherosclerosis, and occult embolism remain alternative or additional mechanisms. The patient received dual antiplatelet therapy followed by aspirin, statin therapy, and rehabilitation. This case emphasizes the limitations of the NIHSS in posterior circulation stroke and the importance of evaluating the craniovertebral junction when a V3 lesion occurs near upper cervical structural disease.

Neurology International doi: 10.3390/neurolint18090172

Authors: Viswabhaskar Susarla Mariah George Ananthi Rathinam Danish Bhatti

Background: Genetic testing in autism spectrum disorder (ASD) can reveal a wide range of chromosomal and sequence-level abnormalities, yet large real-world neurology cohorts rarely report the full spectrum of findings alongside clinical correlates and patterns of testing. We characterized genetic findings in an 1884-patient ASD cohort and examined factors associated with both abnormal findings and the use of genetic testing. Methods: This retrospective cross-sectional study included 1884 patients. Genetic testing was performed in 1011 patients; the primary outcome was an abnormal versus normal genetic result among those tested. All 371 abnormal findings were catalogued in a de-identified supplement. The primary multivariable model included age, sex, seizure history, and EEG abnormality (N = 901); an MRI-inclusive sensitivity model used 422 complete cases, and a separate full-cohort model evaluated factors associated with genetic testing. Results: Abnormal genetic findings were documented in 371/1011 tested patients (36.7%, 95% CI 33.7–39.8%). In the primary model, female sex (aOR 1.483, 95% CI 1.089–2.018; p = 0.012) and seizure history (aOR 1.634, 95% CI 1.136–2.352; p = 0.008) were independently associated with abnormal findings, whereas EEG abnormality was not significant after adjustment (aOR 1.373, p = 0.084). In the MRI-inclusive sensitivity model, female sex and seizure history remained significant, while MRI abnormality was not independently associated (aOR 1.235, p = 0.302). Genetic testing was more common among patients who also underwent EEG or MRI (both p < 0.001). Conclusions: More than one-third of tested patients had an abnormal genetic finding, spanning a broad range of copy-number, sequence, homozygosity, Fragile X-related, chromosomal, and syndromic findings. Seizure history and female sex were the principal adjusted correlates of abnormal findings. Genetic testing clustered with EEG and MRI use, reflecting observed patterns of neurological work-up within this cohort rather than temporal or causal relationships.

Neurology International doi: 10.3390/neurolint18090171

Authors: Ülkü Figen Demir Fatmanur Karakuş Dilbaz

Background/Objectives: Alzheimer disease (AD) causes progressive cognitive and functional loss and substantial caregiver and healthcare burden. Anti-amyloid monoclonal antibodies represent a shift toward biology-directed treatment in biomarker-confirmed early symptomatic AD, but modest clinical effects must be balanced against amyloid-related imaging abnormalities (ARIA), intensive monitoring, and implementation burden. Heterogeneity in trial populations, endpoints, dosing, stopping rules, and follow-up complicates interpretation. This narrative review critically integrates efficacy, safety, durability, biomarker, and implementation evidence for lecanemab and donanemab while preserving study-family relationships and avoiding unsupported cross-trial superiority claims. Methods: For this revised narrative review, a targeted PubMed/MEDLINE search covering the period from database inception was initially conducted before manuscript submission and was subsequently updated through 21 August 2026, supplemented by reference-list and citation tracking. Search terms combined Alzheimer disease with lecanemab, donanemab, anti-amyloid monoclonal antibody, ARIA, APOE, amyloid PET, open-label extension, real-world, clinical meaningfulness, implementation, and access. Sixty-two sources were purposively selected for a comprehensive narrative synthesis; no meta-analysis or formal certainty grading was performed. Results: Pivotal trials demonstrated statistically significant but modest average slowing of decline: Clarity AD showed a 0.45-point between-group difference in CDR-SB worsening at 18 months, and TRAILBLAZER-ALZ 2 showed a 3.25-point iADRS difference in the low/medium-tau population at 76 weeks. ARIA-E occurred in 12.6% of lecanemab-treated and 24.0% of donanemab-treated participants in the pivotal trials, with higher risk in APOE ε4 carriers. Extensions and biomarker analyses suggest persistent biological effects but are less secure for causal inference, and real-world evidence is currently more mature for lecanemab. Conclusions: Both antibodies substantially reduce amyloid and modestly slow average clinical decline in selected patients, but neither restores lost function, greater amyloid clearance does not establish greater individual benefit, and cross-trial superiority cannot be inferred. Treatment requires biomarker-guided selection, APOE-informed risk counseling, serial MRI, infusion and ARIA-management capacity, and shared decision-making that incorporates cost, access, and patient/caregiver burden.

Neurology International doi: 10.3390/neurolint18090170

Authors: Yasar Ünsal Kadir Çetinkaya Mehmet Özgür Özates Oktay Gürcan Oktay Algın Gıyas Ayberk

Background: Early residual or recurrent aneurysm filling remains an important limitation after endovascular treatment of intracranial aneurysms, particularly in large and complex lesions. This study descriptively evaluated 6-month early residual or recurrent filling after coil embolization, stent-assisted coiling, flow-diverting stents, and the Woven EndoBridge (WEB) device in a single-center cohort. Methods: We retrospectively analyzed 151 patients with 161 intracranial aneurysms treated between January 2019 and July 2023. Follow-up imaging at approximately 6 months was performed using computed tomography angiography or magnetic resonance angiography, with digital subtraction angiography when residual filling was suspected. Aneurysm occlusion was evaluated using the Raymond–Roy Occlusion Classification. Clinical, morphological, anatomical, and treatment-related variables associated with early residual or recurrent aneurysm filling were analyzed. Results: Complete occlusion was achieved in 149 aneurysms (92.5%), whereas early residual or recurrent filling occurred in 12 aneurysms (7.5%). Residual or recurrent filling was observed in 4/35 aneurysms treated with coil embolization (11.4%), 1/58 treated with flow-diverting stents (1.7%), 7/60 treated with the WEB device (11.7%), and none of the 8 aneurysms treated with stent-assisted coiling; overall rates did not differ significantly among treatment modalities (p = 0.104). Aneurysm height > 10 mm was significantly associated with early residual or recurrent filling (p = 0.005), and mean aneurysm height was greater in aneurysms with residual or recurrent filling than in completely occluded aneurysms (p = 0.048). In the ICA subgroup, residual or recurrent filling was more frequent after WEB treatment than after other endovascular modalities (p = 0.019). This subgroup signal was based on sparse observations. Conclusions: Aneurysm height > 10 mm was significantly associated with early residual or recurrent aneurysm filling. No statistically significant difference in early residual or recurrent filling was detected among treatment groups. Given the retrospective design, non-random treatment allocation, heterogeneous aneurysm phenotypes, and non-uniform imaging follow-up, these data should be interpreted as a descriptive institutional experience rather than evidence of comparative superiority or equivalence. The ICA subgroup finding is preliminary and hypothesis-generating.

Neurology International doi: 10.3390/neurolint18090169

Authors: Olja Mirkovic Milos Stepovic Jovana Milosavljevic Maja Vulovic Ivana Zivanovic-Macuzic Dejan Aleksic Milos N. Milosavljevic Melanija Tepavcevic Ivona Marinkovic Simonida Delic Kristijan Jovanovic Verica Vukicevic Ana Tomic Miljana Maric Jelena Kostic

Background/Objectives: Vertebral artery hypoplasia is a common congenital anatomical variant of the vertebral arteries, traditionally considered a benign finding. However, accumulating evidence suggests that VAH may influence vertebrobasilar hemodynamics and contribute to susceptibility to posterior circulation disorders. This systematic review aimed to synthesize current evidence regarding the epidemiology, hemodynamic significance, neurological manifestations, and cerebrovascular outcomes associated with VAH. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and registered in PROSPERO (CRD420261442242). A systematic search of PubMed/MEDLINE was performed from database inception to 8 June 2026, supplemented by manual reference screening and targeted searches. Studies evaluating VAH diagnosed using vascular imaging or anatomical assessment, including CTA, MRA, Doppler ultrasonography, and DSA, were eligible. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools, and the level of evidence was classified according to the Oxford Centre for Evidence-Based Medicine framework. Results: Forty-six studies were included in the qualitative synthesis. VAH prevalence varied substantially according to imaging modality, diagnostic criteria, and study population, ranging from approximately 3% to nearly 50%. Across clinical cohorts, VAH was frequently associated with posterior circulation ischemic stroke, transient ischemic attack, and vertebrobasilar insufficiency. Hemodynamic studies demonstrated reduced vertebral artery flow, increased vascular resistance, impaired cerebrovascular reactivity, and altered collateral flow redistribution. VAH was also associated with vestibular disorders, non-stroke neurological syndromes, vertebral artery dissection, and other cerebrovascular anatomical variations. Unlike previous reviews focusing primarily on prevalence or stroke associations, this review integrates epidemiological, anatomical, hemodynamic, computational, and neurological evidence within a unified clinically oriented framework and proposes an evidence-informed conceptual model of VAH as a context-dependent low-flow vascular susceptibility phenotype. Conclusions: Current evidence indicates that VAH represents a clinically relevant vascular susceptibility phenotype rather than merely an incidental anatomical variant. Its clinical significance appears to depend on the interaction between reduced vertebral artery flows, collateral capacity, vascular remodeling, and acquired cerebrovascular risk factors. Standardized diagnostic criteria and prospective multimodal studies are required to define its role in future cerebrovascular risk assessment.

Neurology International doi: 10.3390/neurolint18090168

Authors: Jehan Alrahimi Yara Mualla Alawiah Alhebshi Hind A. Alnajashi Kawther Zaher

Background: Systemic inflammation contributes to the pathobiology of multiple sclerosis (MS), yet serum biomarker data from Middle Eastern populations remain limited. This study evaluated serum levels of IL-6, IL-16, IL-18, and IL-36 in Saudi adults with MS compared with matched healthy controls and examined associations with disease duration, phenotype, treatment, and disability. Methods: This single-center, cross-sectional, matched case–control study enrolled 26 MS patients and 26 age- and sex-matched controls. Serum cytokines were measured by ELISA. Disability was assessed using EDSS and the Timed 25-Foot Walk (T25FW). Matched comparisons used Wilcoxon signed-rank tests; subgroup comparisons used Wilcoxon rank-sum or Kruskal–Wallis tests; associations used Spearman’s correlation. Results: No correction for multiple comparisons was applied given the exploratory design. All four interleukins were higher in MS patients than in controls (p < 0.001). Age correlated with EDSS (r = 0.573, p = 0.002) and T25FW (r = 0.464, p = 0.014). Only IL-6 showed a notable correlation with disability, with T25FW (r = 0.53, p = 0.008) and, weaker, EDSS (r = 0.38, p = 0.052); IL-18 showed a weak, non-significant correlation with T25FW (r = 0.35, p = 0.126); IL-16 and IL-36 showed no relevant associations. IL-16 was higher in newly diagnosed than in long-standing cases (p = 0.012); no differences by phenotype or treatment were observed for any marker. Conclusions: Serum IL-6, IL-16, IL-18, and IL-36 were elevated in Saudi MS patients versus controls. IL-6 alone showed a modest, unadjusted association with disability, supporting its evaluation as a candidate biomarker in larger, longitudinal, covariate-adjusted cohorts. These findings are hypothesis-generating and should not be interpreted as evidence of independent or clinically actionable biomarker utility.

Neurology International doi: 10.3390/neurolint18090167

Authors: Anna Farella Gianvito Lagravinese Valerio Manippa Paola Santacesaria Rosanna Falcone Maria Concetta Schiavariello Pietro Fiore Giorgia Francesca Scaramuzzi Stefania De Trane Paolo Taurisano

Background/Objectives: Unilateral Spatial Neglect (USN) is a disabling attentional syndrome occurring after cortical or subcortical stroke, including thalamic lesions. EEG-based neurofeedback (EEG-NF) may support cortical self-regulation, but evidence in spatial neglect remains limited. This case report describes the clinical, neuropsychological, functional, and electrophysiological (quantitative EEG, qEEG) evolution of a patient with USN after a right thalamic hemorrhagic stroke who underwent multidisciplinary rehabilitation including EEG-NF. Methods: A 70-year-old patient underwent a 3-week inpatient multidisciplinary rehabilitation program including physiotherapy, speech and swallowing therapy, conventional cognitive stimulation, and 15 adjunctive EEG-NF sessions. Baseline and post-treatment assessments included clinical, neuropsychological, neglect-specific, functional, affective, and resting-state qEEG measures. Individual change was examined using the Reliable Change Index when suitable psychometric parameters were available, together with published normative and clinical thresholds. Results: After rehabilitation, the Montreal Cognitive Assessment total raw score increased from 20 to 24, reaching the published minimal clinically important difference but not the minimal detectable change. The Frontal Assessment Battery increased from 8 to 12; after adjustment for age and education according to Italian normative data, both scores remained below the normative cut-off. Neglect-specific measures showed reduced spatial asymmetry, increased contralesional target detection, and a Catherine Bergego Scale reduction from 17 to 5, indicating a shift from moderate to mild ecological neglect. Functional independence improved, with reliable change in Functional Independence Measure (FIM) total and cognitive scores and Modified Barthel Index scores. Exploratory qEEG analyses showed condition-dependent spectral and connectivity changes, but findings were heterogeneous and hypothesis-generating. EEG-NF was completed without adverse events. Conclusions: The adjunctive EEG-NF protocol was completed as planned, with no adverse events. Clinical improvement cannot be attributed specifically to neurofeedback because all rehabilitation components were delivered concurrently. Controlled studies are needed to clarify its specific contribution and the durability of the observed improvements in post-stroke spatial neglect.

Neurology International doi: 10.3390/neurolint18090166

Authors: Lisa B. E. Shields Vasudeva G. Iyer Smita Ghare Christopher B. Shields

Background/Objectives: Iatrogenic brachial plexus injuries (BPI) are known to occur following a host of surgeries, most often during procedures at the shoulder and cardiac procedures with a median sternotomy. The primary mechanisms include overstretching of the brachial plexus, direct trauma, or compression by hematoma or seroma. Our objective was to determine the pattern of iatrogenic BPI in patients referred to us for electrodiagnostic (EDX) evaluation. Methods: This is a review of 52 patients who were referred to our Neurodiagnostic Center for an iatrogenic BPI over a 16-year (9 July 2010–17 June 2026) period. All patients underwent a clinical examination and EDX studies. Results: The most frequent etiologies of the iatrogenic BPI were shoulder surgery in 28 [53.8%] patients and coronary artery bypass graft procedures with a median sternotomy in 13 [25.0%] patients. The topography of brachial plexus involvement was trunks in 22 (42.3%) and cords in 12 (23.1%). Ten (19.2%) patients had a pan-plexopathy, and the remaining eight (15.4%) patients had multiple sites involving the trunks, cords, and branches. The majority (48 [92.3%]) of patients sustained a stretch injury of the brachial plexus, and four (7.7%) sustained a direct injury. A total of 48 (92.3%) patients had reduced motor unit potential recruitment and/or increased polyphasic motor units on needle EMG, and a similar number had an absence of or low amplitude sensory nerve action potentials. Conclusions: Surgeons should take appropriate precautions to avoid BPI during many surgical procedures especially those of the shoulder and cardiac procedures with a median sternotomy. EDX studies are valuable in detecting and localizing an iatrogenic BPI as well as assessing reinnervation. Preoperative positioning limiting excessive shoulder abduction as well as intraoperative neuromonitoring are measures that may reduce the likelihood of an iatrogenic BPI.

Neurology International doi: 10.3390/neurolint18090165

Authors: Sasithorn Khawprapa Nuttaset Manimmanakorn Yohei Otaka Jittima Saengsuwan

Background: Upper limb spasticity after stroke occurs due to neural hyperexcitability and secondary alterations in muscle properties. Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive technique used to reduce spasticity. This study aimed to compare the effects of rPMS versus sham stimulation on upper limb spasticity and muscle stiffness using shear wave elastography (SWE). Methods: This prospective, double-blind randomized controlled trial included 32 stroke patients with upper limb spasticity (Modified Ashworth Scale (MAS) ≥ 2 in the elbow flexors), who received rPMS or sham stimulation in addition to conventional rehabilitation (n = 16 per group). Spasticity was assessed using MAS, and muscle stiffness using SWE. Results: The rPMS group showed a transient short-term reduction in upper limb spasticity compared with the control group at the end of treatment (p = 0.045); however, this effect was not sustained at the 2-week follow-up. No significant between-group differences were observed in muscle stiffness, upper limb motor function, or activities of daily living. Conclusions: This study provides preliminary evidence that rPMS may produce a transient, short-term reduction in upper limb spasticity after stroke. However, this effect was not sustained at follow-up or accompanied by significant improvements in muscle stiffness or functional outcomes.

Neurology International doi: 10.3390/neurolint18090164

Authors: Lejla Zonić Renata Hodžić Dževdet Smajlović Larisa Kovačević Samra Kadić-Vukas Lejla Tandir-Lihić Mirsad Hodžić

Methods: This retrospective–prospective study included 90 patients with BT. Based on the type of BT, the participants were divided into three groups of 30 patients each: patients with gliomas, with meningiomas and with brain metastasis. Demographic data such as age, sex, alcohol and cigarette consumption were collected. In all three study groups, the time of onset of the first ES, type, characteristics, and frequency were analyzed as well as abnormalities on electroencephalography (EEG). EEG was reviewed for any abnormal background or interictal epileptic discharges. Results: Brain tumor-related epilepsy (BTRE) was present in 46.7% of patients. The incidence of epilepsy secondary to brain tumors was 66.7% in patients with gliomas, 46.6% in those with meningiomas, and 26.7% in those with metastasis. The tumors associated with BTRE were most commonly located in the frontal (40%) and temporal (32.2%) lobes, followed by the parietal (25.6%) and occipital (2.2%) lobes. Focal to bilateral tonic–clonic ES represented the most common seizure type among the studied patients. Abnormalities on the initial EEG recordings were observed in 33 patients with BTRE. Focal EEG abnormalities were identified in 54.7% of patients, while diffuse changes were present in 23.8% of patients (p < 0.005). Conclusions: The highest incidence of BTRE was observed in patients with gliomas, followed by those with meningiomas, while the lowest incidence was recorded in the group with metastases. Smaller and slower growing tumors were associated with higher incidence of seizures than larger, more rapidly growing lesions. Focal to bilateral tonic–clonic seizures were the most common seizure type among patients with BTRE.

Neurology International doi: 10.3390/neurolint18090163

Authors: Giulia Del Duca Marta Camici Isabella Sperduti Anna Clelia Brita Martina Maresca Carmela Pinnetti Ilaria Mastrorosa Valentina Mazzotta Andrea Antinori

Introduction: Cognitive dysfunction (“brain fog”) is a common manifestation of post-acute COVID-19 syndrome (PACS) and may persist long after the acute infection. While cross-sectional studies have described cognitive deficits, longitudinal evidence on recovery trajectories remains limited. Methods: We conducted a longitudinal observational study of neurocognitive performance and neuropsychiatric symptoms in patients with PACS. Participants underwent assessment with 20 standardized tests covering five cognitive domains (memory, attention, language, executive functions, psychomotor processing speed); anxiety, depression, and sleep quality were assessed at three time points. Changes were analysed using the Friedman test. Results: Forty-two patients were included (median age 57 years; 35.7% female) from a predominantly hospitalized cohort (81% hospitalised; 66.7% requiring respiratory support). Patients who completed all three assessments (completers, n = 42) were compared with those who attended the first evaluation but did not complete follow-up (non-completers, n = 544); completers were more severely ill during the acute phase rather than healthier or more motivated. At the group level, statistically significant improvements over time were observed across the whole sample in verbal short-term learning, visuospatial memory, working memory, constructional praxis, phonological verbal fluency, and psychomotor processing speed (all p ≤ 0.05); after Benjamini–Hochberg adjustment across the twenty cognitive outcomes, visuospatial span forward and backward and psychomotor processing speed remained significant (all FDR-adjusted p ≤ 0.013), with the change confined to the first six months. Sleep quality also improved (p < 0.0001). Conclusion: In this cohort, group-level performance improved in six of the twenty tests administered, of which three remained significant after correction for multiple comparisons, while 28 of 42 patients (66.7%) still scored in the impaired range on at least one test at 12 months, and 17 (40.5%) on two or more. These findings highlight the importance of long-term neuropsychological monitoring and integrated cognitive-psychiatric evaluation in post-COVID care. Given the small, predominantly hospitalized sample, improvements should be interpreted cautiously and confirmed in larger controlled studies, although the use of alternate forms for part of the battery makes task-specific learning an incomplete explanation.

Neurology International doi: 10.3390/neurolint18090162

Authors: Kanta Kitabayashi Naoto Ogura Naoki Yoshioka Wataru Kakuda

Objectives: We developed an original protocol for standing balance and walking function training using immersive virtual reality (IVR) combined with a bodyweight-supporting (BWS) system. The purpose of this study was to evaluate the feasibility of IVR training in poststroke patients and to identify clinical characteristics associated with walking improvement. Methods: A total of 22 poststroke patients admitted to a rehabilitation ward were enrolled. All participants received conventional physical therapy daily, and IVR training was initiated when balance recovery plateaued. The original IVR training was conducted for 10 consecutive days using a BWS system, enabling safe and repetitive practice of standing weight shifting and advanced stepping tasks, with task difficulty individually adjusted. Primary outcomes were the Berg Balance Scale (BBS), Functional Reaching Test (FRT), and walking time on the 10-m walk test (10 MWT). Changes in 10 MWT (Δ10 MWT) were calculated, and participants were dichotomized into good and poor walking improvement groups based on Δ10 MWT to compare baseline clinical characteristics (e.g., BBS, FRT, and Functional Ambulation Categories [FAC]) between the groups. Receiver operating characteristic (ROC) curve analyses were conducted to identify cutoff values associated with greater improvements in walking. Results: BBS, FRT, and 10 MWT improved significantly after the 10-day IVR training (p < 0.01). ROC analyses identified FAC ≤ 3 and BBS ≤ 42 before training as cutoff values associated with greater improvement in walking performance. Conclusions: Our proposed IVR training approach using a BWS system could be safely implemented and might improve standing balance and walking function in poststroke patients with a balance disability.

Neurology International doi: 10.3390/neurolint18090161

Authors: Bartosz Migda Michał Kutyłowski Natalia Madetko-Alster Anna Migda Karol Kutyłowski Piotr Alster

Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy in which neurodegeneration may be accompanied by neuroinflammatory and peripheral immune alterations. Whether peripheral inflammatory activity reflects structural degeneration within vulnerable brain networks remains unclear. Methods: This retrospective case–control study included 12 patients with PSP and 12 patients with Parkinson’s disease (PD). Automated volumetric analysis of 3-Tesla MRI was performed using volBrain 2.0. Blood-derived inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and red blood cell distribution with coefficient of variation (RDW-CV). Results: Patients with PSP showed significantly lower normalized superior frontal gyrus and pallidal volumes than patients with PD. Within the PSP group, higher values of selected blood-derived inflammatory indices were associated with lower frontal network volumes. After adjustment for age, MLR was inversely associated with the composite Frontal Network Score (partial r = −0.7333, p = 0.0067, FDR q = 0.020). The strongest regional association was observed between SIRI and medial frontal cortex volume (rho = −0.748, p = 0.0051); however, regional associations did not remain significant after FDR correction. Conclusions: Peripheral inflammatory markers were associated with MRI-derived measures of frontal network degeneration in PSP. The association between MLR and the composite Frontal Network Score supports a link between systemic immune alterations and network-level neurodegeneration in PSP.

Neurology International doi: 10.3390/neurolint18090160

Authors: Ana Cruz Cruz Julio Perez-Villegas Eduardo Alvarado Edward Smith Ivan Dueñas-Pacheco

Background/Objectives: To describe the demographic, clinical, and epidemiological characteristics of a cohort of patients diagnosed with Multiple Sclerosis (MS) in Lima, Peru. Methods: A descriptive, retrospective cohort study conducted across three major hospitals in Lima. We included adult patients diagnosed with MS in any of its clinical phenotypes—Clinically Isolated Syndrome (CIS), Relapsing-Remitting MS (RRMS), Secondary Progressive MS (SPMS), and Primary Progressive MS (PPMS)—who were followed between 2007 and 2017. Results: A total of 103 patients were identified. The majority were women (58.3%), with a median age at onset of 38.4 years (Interquartile Range [IQR]: 28.9–46.5). The most common clinical phenotype at onset was RRMS (90.3%), which remained the most prevalent phenotype at the current evaluation (79.6%). Twelve patients (12.9%) progressed from RRMS to SPMS by their last control visit. The most frequent symptoms at onset were limb weakness (72.8%), sensory symptoms (72.8%), and blurred vision (42.0%). At the last evaluation, the most frequent symptoms were limb weakness (78.6%), sensory symptoms (71.8%), and spasticity (40.2%). The most common initial treatment was interferon-beta (44.7%), while two patients (1.9%) initiated therapy with a highly effective disease-modifying drug (DMD), Ocrelizumab. The most recent treatment reported remained interferon-beta (33.9%), but 12 patients (11.7%) were currently receiving Ocrelizumab. Conclusions: This study describes clinical characteristics at onset and during follow-up that are largely similar to those reported in international series. However, we found no evidence of improved disease evolution, a finding potentially attributable to the heterogeneity of treatment and management strategies employed across the cohort.

Neurology International doi: 10.3390/neurolint18090159

Authors: Viswabhaskar Susarla Mariah George Ananthi Rathinam Danish Bhatti

Background: Brain MRI in patients with autism spectrum disorder (ASD) is generally considered when additional neurologic, developmental, or syndromic concerns warrant structural evaluation. In the study practice, ASD alone was not used as the reason to obtain MRI. We examined documented MRI use and broad result coding while explicitly separating selection for imaging from abnormal-result status. Methods: This retrospective specialty-practice cohort included 1884 patients with ASD. The primary outcome was the proportion of documented MRI examinations coded abnormal. Secondary analyses examined associations of age, sex, seizure history, EEG status, and genetic test status with abnormal versus normal MRI coding and with documented MRI utilization. MRI categories and the pediatric restriction were exploratory and sensitivity analyses. Results: An MRI result was recorded for 704 patients (37.4%; 95% CI 35.2–39.6); 322 were coded abnormal (45.7%; 95% CI 42.0–49.5). The abnormal-result models had low in-sample discrimination (AUC 0.528 and 0.553), and adjusted confidence intervals for all measured variables included 1.00; these results do not demonstrate equivalence between clinical groups. Seizure history was associated with documented imaging in the full cohort (aOR 2.47, 95% CI 1.94–3.14), and abnormal EEG was associated in the exploratory complete-case utilization model (aOR 2.83, 95% CI 1.93–4.14). Conclusions: Broad MRI abnormalities were frequent among patients selected for imaging because of additional clinical concerns, but a broad abnormal code is not equivalent to clinically actionable yield. The routinely captured variables available in this dataset were insufficient to distinguish abnormal from normal MRI coding. These findings favor individualized MRI decisions based on the clinical question prompting imaging and motivate future studies with richer neurologic and developmental phenotyping.

Neurology International doi: 10.3390/neurolint18080158

Authors: Elena Aidinoff Almothana Khatib Anna Oksamitni Ilana Gelernter Lilach Front Amiram Catz Sharon Shaklai Marina Motin Corinne Serfaty Deborah Rubin-Asher

Background/Objectives: Patients with prolonged disorder of consciousness (PDOC) who regained consciousness in intensive care for consciousness rehabilitation (ICCR) were referred to further brain rehabilitation (FBR). The current retrospective cohort study evaluated the functional and cognitive outcomes of FBR. Methods: We assessed outcomes in 258 PDOC patients during FBR and used multivariate regression analyses to examine the influence of demographic and clinical characteristics on outcomes. Results: During FBR, Functional Independence Measure (FIM) motor, cognitive, and total scores improved from 21 ± 11, 11 ± 10, and 32 ± 15 to 43 ± 26, 18 ± 7, and 61 ± 32, respectively (p < 0.001). Dynamic Lowenstein Occupational Therapy Cognitive Assessment (DLOTCA) total scores increased from 57 ± 29 to 82 ± 36, and the average 6-min-walk (6MW) distances improved from 295 to 374 m (p < 0.001). Higher discharge FIM and DLOTCA scores were associated with younger age, traumatic etiology of the brain injury, shorter time to regaining consciousness, and higher FIM and DLOTCA scores at admission to FBR (p < 0.05). Conclusions: We observed functional and cognitive improvement in the examined patients. The improvement was associated with factors that may mainly reflect the severity of brain damage. The findings support continuing rehabilitation before and after emerging from PDOC.

Neurology International doi: 10.3390/neurolint18080156

Authors: Janak Patel Stephanie Liang Mirza Bulic May Kim-Tenser Tatsuhiro Fuji Sukgu Han Benjamin Emanuel Fawaz Philip Tarzi

Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor and somatosensory-evoked potential facilitates early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair.

Neurology International doi: 10.3390/neurolint18080157

Authors: Faisal Sawab Tim Lampmann Haitham Alenezi Lars Eichhorn Mohammed Banat Hartmut Vatter Marcus Thudium Motaz Hamed

Background/Objectives: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical disorders in older adults and remains associated with a relevant recurrence rate despite standardized surgical treatment. Identifying postoperative factors that predict recurrence may improve postoperative surveillance and surgical strategy. We therefore investigated whether the density of the residual hematoma on early postoperative computed tomography (CT) is associated with recurrence after burr-hole trepanation. Methods: We retrospectively analyzed all consecutive patients who underwent burr-hole trepanation for cSDH at our institution between 2016 and 2021. Residual hematoma density was measured in Hounsfield units (HU) on postoperative CT scans. Recurrence was defined as symptomatic hematoma reaccumulation requiring reoperation. Results: A total of 223 patients met the inclusion criteria. The overall recurrence rate was 20.2%. Mean residual hematoma density was significantly higher in the recurrence group than in the non-recurrence group (23.2 ± 13.1 HU vs. 19.0 ± 9.1 HU; p = 0.005). ROC analysis identified an optimal cutoff value of 19 HU (AUC 0.578, 95% CI 0.511–0.645; p = 0.022) with sensitivity of 57.8%, and a specificity of 57.9%. Patients with residual hematoma density ≥19 HU had a significantly higher recurrence rate than those with lower density (25.7% vs. 15.6%; p = 0.043). In multivariable logistic regression, higher residual density remained an independent predictor of cSDH recurrence (p = 0.008, OR 1.9; 95% CI 1.2–3.0). Conclusions: Higher postoperative residual hematoma density is an independent predictor of recurrence after burr-hole trepanation for cSDH. Residual density on early postoperative CT may serve as a simple and clinically accessible imaging marker of incomplete hematoma clearance and may help refine postoperative risk assessment. Nevertheless, the low AUC limits interpretation of predictive performance.

Neurology International doi: 10.3390/neurolint18080155

Authors: Balaganesh Natarajan Mahika Khurana Mariam Gabadadze Ahmed Abd Elazim Eman Elmasry Eldamarany Khalifa

Isolated cortical vein thrombosis is a rare subtype of cerebral venous thrombosis with highly variable clinical and radiologic manifestations that frequently delay diagnosis. Bilateral thrombosis of the veins of Trolard is exceptionally uncommon, with only a few cases reported in the literature. We report a 64-year-old right-handed man who presented after being found unresponsive with suspected seizure. Although his neurological examination was normal at evaluation (NIHSS 0), noncontrast CT demonstrated subtle bilateral cortical vein hyperdensities (cord sign). Subsequent MRI and MR venography confirmed bilateral thrombosis of the veins of Trolard with associated venous congestion and a small sulcal subarachnoid hemorrhage. The patient was treated with therapeutic anticoagulation and levetiracetam. The patient achieved an excellent functional outcome (modified Rankin Scale score of 0). At 3-month follow-up, he remained neurologically intact without recurrent seizures. Follow-up MRI demonstrated improvement of the cortical FLAIR abnormality, and MR venography showed significant interval improvement in the bilateral vein of Trolard thromboses with residual short-segment nonocclusive filling defects, consistent with partial venous recanalization. This case expands the recognized clinical spectrum of the bilateral vein of Trolard thrombosis by demonstrating that extensive bilateral cortical venous involvement may present predominantly with seizure despite a normal neurological examination (NIHSS 0). Early recognition of subtle CT findings, confirmation with dedicated venous imaging, and prompt anticoagulation can result in excellent clinical recovery and favorable radiographic evolution.

Neurology International doi: 10.3390/neurolint18080154

Authors: Hunor-Pál Fodor Beáta Albert Pál Salamon

Background/Objectives: Brain-derived neurotrophic factor (BDNF) and antioxidant networks mediated by Selenoprotein P (SEPP1) are core drivers of structural neuroplasticity and blood–brain barrier integrity, yet their co-regulatory behavior during subacute stroke neurorehabilitation remains poorly understood. This pilot study quantified concurrent changes in serum BDNF and SEPP1 during rehabilitation. Methods: Sixteen subacute post-stroke patients with mild stroke severity were assigned to an intensive multi-modal neurorehabilitation protocol incorporating high-intensity interval training (Treated, n = 7) or standard care (Control, n = 9); the biomarker sampling window averaged 73.4 days. Fasting venous blood was collected at baseline and post-intervention and analyzed by ELISA. Results: BDNF changes (ΔBDNF) differed significantly between arms (U = 57.0, p = 0.0081): the Treated cohort showed a uniform decrease (mean Δ: −0.240 ± 0.103 ng/mL), while Controls showed stabilization or a slight increase (mean Δ: +0.118 ± 0.339 ng/mL). ΔBDNF and ΔSEPP1 were significantly, positively correlated across the cohort (ρ = 0.596, p = 0.015). Conclusions: The BDNF decline in the Treated group is consistent with the “central sink” hypothesis, but may more plausibly reflect stress/cortisol-mediated suppression induced by the high training intensity, contrasting with increases typically reported after moderate-intensity subacute-phase exercise. The collinear coupling with SEPP1 suggests a link between neurotrophic synthesis and antioxidant buffering during post-stroke tissue remodeling, though this correlational finding does not by itself establish a single, coordinated mechanism.

Neurology International doi: 10.3390/neurolint18080153

Authors: Camilla Biering Lundquist Lars Evald Simon Svanborg Kjeldsen Lis Viborg Rasmus Langelund Jørgensen Jesper Fabricius

Objectives: To determine the prevalence of visual deficits among inpatients with acquired brain injury, to examine the agreement between objective screenings and patient-reported visual deficits, and to investigate patient characteristics associated with visual deficits. Methods: This cross-sectional study included data on screened and patient-reported visual deficits in patients with acquired brain injury admitted for inpatient rehabilitation. The screenings were conducted by occupational therapists. Visual acuity and visual field were assessed in 2014–2023, and complemented by assessment of ocular motility and patient-reported deficits in 2021–2023. Predictive values were calculated for the agreement between screening results and patient-reported symptoms. Logistic regression models were applied to investigate the association between clinical characteristics and visual deficits. Results: 2814 patients were screened, 65% were men, the median age was 64 years, and the most common diagnosis was stroke (66%). In screened patients 32% had reduced visual acuity, 18% had ocular motility deficits, and 15% had visual field deficits. Of 975 patients providing self-reports, 38% reported vision problems. A total of 28% of patients who did not report visual deficits, had visual deficits in the objective screening. Lower functional level was associated with greater odds of having any visual deficits. Traumatic and anoxic brain injuries were associated with lower odds of visual field deficits compared with stroke. Conclusions: The high proportion of patients with visual deficits underlines that these are common consequences following acquired brain injury. Objective screening and patient-reported deficits offer overlapping yet distinct insights into visual deficits. Knowledge of clinical characteristics associated with visual deficits may help recognize high-risk subgroups.

Neurology International doi: 10.3390/neurolint18080152

Authors: Vasudeva G. Iyer Lisa B. E. Shields Smita Ghare Christopher B. Shields

Background/Objectives: Ulnar nerve neuropathy at the elbow (UNE) is the second most common focal neuropathy of the upper extremity and often results from entrapment of the ulnar nerve as it traverses the elbow with insidious onset and gradual progression. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in a cohort of patients presenting with acute UNE. Methods: This is a review of 103 patients with clinical features of UNE with acute onset who underwent EDX and US studies over a 25-year period (2010–2026) at our Neurodiagnostic Center. Results: Of the 103 patients with acute UNE, all experienced paresthesia in the ulnar nerve distribution. A total of 27 (26.2%) patients had elbow pain, and 99 (96.1%) had decreased pinprick sensation in the ulnar nerve distribution. Weakness of the following muscles was detected: abductor digiti minimi (ADM) (94 [91.3%]), FDI (first dorsal interosseous) (91 [88.3%]), and FDPu (flexor digitorum profundus—ulnar) (76 [73.8%]). Most patients had a clinical grade of 3 (severe: sensory and motor abnormalities as well as atrophy of the FDI and ADM muscles) (93 [90.3%]). Perioperative injuries were the most common etiology of acute UNE, consisting of 65 (63.1%) patients. The perioperative injury was noted after surgical procedures at varied locations, most frequently at the shoulder in 23 (35.4%) followed by coronary artery bypass in 9 (13.8%) and knee joint surgery in 8 (12.3%). Non-iatrogenic injuries affected 11 (10.7%) patients. The US study revealed cysts and tumors such as a Schwannoma in 14/76 (18.4%) patients. Focal demyelination was observed by EDX studies in 95 (92.2%) patients, and a conduction block was detected in 24 (23.3%). Motor and sensory axonal involvement was identified in 81 (78.6%) and 86 (83.5%) patients, respectively. Of the 76 patients who underwent an US study, 68 (90.6%) had an increase in the cross-sectional area of the ulnar nerve and 51 (68.0%) had a hypoechoic ulnar nerve at the elbow. Conclusions: In this study, the most common cause of acute UNE was periprocedural injury, most frequently following shoulder surgery. Acute UNE may also occur without a history of antecedent trauma or a surgical procedure. EDX and US studies provide complementary data to determine the severity and the etiology of acute UNE and guide further management.

Neurology International doi: 10.3390/neurolint18080151

Authors: Alessandro Tozzi Valentina Caldiera Giuseppe Ganci Paolo Ferroli Marco Schiariti Matteo Milani Isabella Canavero Benedetta Storti Anna Bersano Francesco Acerbi Elisa Francesca Maria Ciceri

Background: Flow diverters (FDs) are widely used to treat intracranial aneurysms. Although effective, FD-related thrombosis or progressive stenosis may lead to acute or delayed cerebral hypoperfusion with significant neurological morbidity. Management options are limited when medical or endovascular rescue strategies fail. This study aims to evaluate the role of extracranial–intracranial bypass (EC-IC bypass) as a rescue strategy across the spectrum of FD-related cerebral hypoperfusion. Methods: We retrospectively reviewed all patients who underwent EC-IC bypass for FD-related cerebral hypoperfusion over a 10-year period in our institution. Both acute and chronic presentations were included. Clinical status was assessed using the modified Rankin Scale (mRS). Imaging evaluation included digital subtraction angiography (DSA), computed tomography angiography (CTA), magnetic resonance angiography (MRA) and quantitative magnetic resonance imaging for bypass flow assessment. Surgical technique, antiplatelet therapy, timing of intervention and clinical outcomes were analysed. Results: Five patients with FD-related cerebral hypoperfusion who underwent superficial temporal artery–middle cerebral artery bypass (STA-MCA bypass) were identified. Two distinct patterns emerged. Three patients developed early hypoperfusion within the first month of FD placement, presenting with acute neurological deficits and treated by emergent or urgent bypass under dual antiplatelet therapy. Two patients developed late hypoperfusion years after the procedure, presenting with progressive haemodynamic symptoms and treated by elective flow-augmentation bypass under aspirin monotherapy. At discharge, only one patient had an mRS ≥ 3. At one-year follow-up, a favourable outcome (mRS ≤ 2) was observed in all patients with available data. Follow-up data were missing for one patient. Conclusions: EC-IC bypass represents a feasible rescue strategy for FD-related cerebral hypoperfusion when medical or endovascular treatments fail. In our experience, though limited, STA-MCA bypass can provide sufficient cerebral reperfusion, even in urgent settings and under dual antiplatelet therapy, leading to favourable neurological outcomes.

Neurology International doi: 10.3390/neurolint18080150

Authors: Pasquale Frisina Valeria Panebianco Filippo Valentini Antonio Iacuzio Carlo Cavaliere Umberto Romeo Iacopo Carbone Lucia Borghetti Daniela Messineo

Background: Isolated hypoglossal nerve palsy is a rare neurological condition with a broad differential diagnosis. Although neoplastic disorders are the most common cause, internal carotid artery dissection (ICAD) is an uncommon but clinically important and potentially reversible vascular etiology that is frequently underrecognized. This systematic review synthesized the available evidence regarding the clinical presentation, imaging findings, pathophysiological mechanisms, treatment, and outcomes of isolated hypoglossal nerve palsy associated with ICAD through a standardized patient-level descriptive analysis. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261364863). PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to April 2026. Manual reference screening and forward citation tracking were also performed. Studies reporting original, patient-level data on isolated hypoglossal nerve palsy associated with ICAD were eligible. Clinical, imaging, treatment, and outcome data were extracted and synthesized descriptively. In hybrid publications combining original case reporting with a narrative literature review, only eligible, original patient data were included in the quantitative synthesis, whereas the narrative review components were used for citation tracking and contextual comparison. Results: A total of 26 standalone primary publications were included, comprising 23 case reports and 3 case series. Two additional hybrid publications each contributed one eligible patient. One hybrid publication contained an original case-report component, whereas the other reported two original cases and was therefore considered to contain a case-series component, although only one of its patients fulfilled the eligibility criteria. Overall, the 28 publications contributed 32 eligible patients to the patient-level quantitative synthesis. The narrative review components of the two hybrid publications were used solely for citation tracking and contextual comparison. Patients were predominantly male (28/32, 87.5%), with a median age of 47 years. Tongue deviation (28/28, 100%) and tongue weakness (30/30, 100%) were the hallmark clinical features, followed by dysarthria (26/26, 100%) and dysphagia (18/22, 81.8%). All patients presented with isolated hypoglossal nerve palsy at presentation, without Horner syndrome or additional lower cranial nerve involvement. MRI was the most frequently reported imaging modality (29/32, 90.6%), whereas CTA was commonly used to characterize luminal abnormalities. Intramural hematoma (25/26, 96.2%), luminal stenosis (23/26, 88.5%), and external arterial enlargement (22/24, 91.7%) were the most consistent neuroradiological findings. Conservative medical management predominated (31/32, 96.9%). The available evidence was more consistent with a compressive mechanism related to subadventitial arterial wall expansion, although an ischaemic contribution involving the vasa nervorum could not be excluded. A favourable clinical outcome (complete recovery or marked improvement) was observed in 21/30 patients (70.0%). Overall, improvement of any degree, including partial recovery, was documented in 25/30 evaluable patients (83.3%). Outcome data should be interpreted cautiously because they derive predominantly from individual case reports. Conclusions: This systematic review provides an updated standardized synthesis of the available case-level evidence on isolated hypoglossal nerve palsy associated with ICAD. CTA and MRI/MRA provide complementary diagnostic information and may facilitate timely diagnosis when interpreted according to the clinical context. The available evidence identifies recurrent clinico-radiological patterns that may assist clinicians in recognizing this uncommon presentation while highlighting the need for prospective multicentre studies to better inform future diagnostic and therapeutic strategies.

Neurology International doi: 10.3390/neurolint18080149

Authors: Kanta Kitabayashi Naoki Yoshioka

In recent years, the application of virtual reality (VR) in rehabilitation medicine has gained increasing attention. VR is generally classified into two types: non-immersive and immersive systems. Non-immersive VR allows patients to interact with virtual environments through screens while maintaining a connection with the real world. Several studies have reported that the combined application of non-immersive VR and adjunctive technologies such as transcranial direct current stimulation and hand exoskeleton devices could facilitate functional recovery of hemiparetic limbs after stroke. In contrast, immersive VR is applied with the use of head-mounted displays to encompass the user’s visual field, providing a high level of immersion and an enhanced sense of presence. This enhanced experience has been shown to promote patients’ attention and motivation, which are important factors in motor learning. Emerging evidence suggests that immersive VR is effective for improving upper limb motor function in post-stroke hemiparetic patients. Furthermore, rehabilitative training performed in immersive virtual environments may facilitate the transfer of acquired motor skills to real activities of daily living. Future research should aim to generate high-quality evidence through large-scale, multicenter randomized controlled trials to better establish the clinical efficacy and optimal implementation of VR-based interventions in stroke rehabilitation.

Neurology International doi: 10.3390/neurolint18080148

Authors: Paula Sánchez-Fernandez Álvaro Astasio-Picado Jesús Jurado-Palomo

Introduction: Stroke remains a leading cause of mortality and long-term disability worldwide. Coordinated care delivered through protocol-driven multidisciplinary teams enables rapid diagnosis and treatment, both of which are essential for improving clinical outcomes. Objective: Our objective was to analyze care strategies in the emergency management of acute ischemic stroke, focusing on treatment times and influencing factors, interventions implemented in emergency settings and their impact on clinical outcomes, and the contribution of healthcare professionals to optimizing stroke care. Methods: A systematic review was conducted in accordance with the PRISMA 2020 Statement. Current evidence published between 2021 and 2026 was retrieved from five databases: PubMed, Web of Science, Scopus, Cochrane Library, and SciELO. Eligibility criteria were applied, and methodological quality and risk of bias were assessed using validated appraisal tools. Results: Fourteen studies involving a total of 6384 patients were included. Factors such as healthcare system reorganization, multidisciplinary teamwork, early protocol activation, and the use of stroke-specific triage scales significantly influenced treatment times. Coordinated and protocolized care pathways, together with evidence-based clinical interventions, were consistently associated with higher thrombolysis rates and shorter treatment times, while improvements in neurological and functional recovery were reported in several, but not all, studies. The integration of specialized stroke professionals and structured emergency care processes contributed to reducing treatment delays and improving patient outcomes. Conclusions: Critical treatment times in acute ischemic stroke are influenced by multiple factors, and targeted organizational and clinical strategies can accelerate diagnosis and treatment. Although improvements in clinical outcomes were not consistently demonstrated across all included studies, the available evidence consistently supports protocol-driven multidisciplinary emergency care as an effective strategy for reducing treatment delays and optimizing acute ischemic stroke management.

Neurology International doi: 10.3390/neurolint18080147

Authors: Hussain Almohammed Husna Irfan Thalib Samiya Khanam Kawthar Faisal Kushara Wejdan Ahmed Aldawsari Hala Omar Algazzawi Rimas Warid Aljuaid Mohammed Ibrahim Almuhaysin Hams Akram Alharbi Alia Alokley

Background and objectives: Cerebrovascular strokes and transient ischemic attacks (TIAs) remain leading causes of global mortality and long-term disability. Emerging evidence suggests that pre-existing structural brain frailty—driven by chronic cerebral small vessel disease (CSVD)—critically limits neuroplastic compensation and determines overall recovery potential. This systematic review aims to synthesize current evidence evaluating brain frailty as an independent determinant of functional and cognitive outcomes. Methods: Following PRISMA and Cochrane SWiM guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, Embase, and Scopus. Methodological quality was evaluated using the Newcastle–Ottawa Scale (NOS). Due to anticipated clinical and methodological heterogeneity, data were synthesized via a structured narrative approach. A total of 15 studies comprising more than 18,000 participants met the inclusion criteria, including prospective cohorts, retrospective cohorts, registry analyses, pooled cohort studies, and post hoc analyses of randomized controlled trials. Results: Structural disconnection burden emerged as one of the strongest predictors of post-stroke cognitive impairment, demonstrating remarkably large effect sizes at both 6 months (OR 9.96, 95% CI 2.21–52.40) and 36 months (OR 12.27, 95% CI 2.80–63.40). Additionally, blood–brain barrier (BBB) leakage was significantly associated with longitudinal cognitive decline (β −3.62 to −0.16, p < 0.001). Pre-existing brain frailty was also consistently associated with poorer functional recovery following acute ischemic stroke, even among patients undergoing advanced reperfusion strategies such as endovascular thrombectomy or intravenous thrombolysis. Conclusions: Brain frailty should be integrated into clinical prognostic frameworks as a key marker for predicting long-term cognitive function and functional independence in stroke patients. However, the substantial methodological and clinical heterogeneity observed across the included literature must be acknowledged as a key limitation of the current evidence base. Large-scale, prospective, multicenter longitudinal studies are required to better standardize brain frailty metrics and validate their utility in clinical practice.

Neurology International doi: 10.3390/neurolint18080146

Authors: Lucille A. Lumley Hailey G. Steier Sabrina Y. Orta Donna A. Nguyen Michael F. Stone Caroline R. Schultz Jerome Niquet Marcio de Araujo Furtado Claude G. Wasterlain

Background/Objective: Status epilepticus (SE) is a life-threatening condition that requires immediate response to effectively control. Although benzodiazepines are the first-line treatment against SE, when treatment is delayed, benzodiazepine pharmacoresistance develops. In preclinical models of benzodiazepine refractory SE, the addition of antiseizure medications (ASMs) as adjunct to midazolam to reduce neuronal excitability and enhance inhibitory function is essential to protect against the neurodegeneration and epileptogenesis that follows prolonged seizure. Brivaracetam is a recently FDA-approved ASM to treat partial onset seizures in pediatric and adult patients as a monotherapy or adjunct therapy. We evaluated the potential of brivaracetam as monotherapy or in combination with midazolam and ketamine for efficacy against organophosphorus nerve agent (OPNA)-induced refractory SE in rats. Methods: Adult male rats were exposed to a seizure-inducing dose of soman and treated with atropine sulfate and the oxime asoxime chloride one minute after soman exposure and with brivaracetam alone or in combination with midazolam and ketamine 40 min after seizure onset. Multiple metrics of protection such as seizure severity, spontaneous recurrent seizure (SRS), neuronal loss, and neuroinflammation were evaluated. Results: Although brivaracetam monotherapy resulted in 100% survival, protection from the development of SRS and neurodegeneration only occurred when brivaracetam was administered as an adjunct to ketamine and midazolam. Initial seizure severity was also reduced by the combination of brivaracetam–midazolam–ketamine over monotherapy. Conclusions: Although further research is needed to determine optimal drug combinations, these preclinical findings provided further evidence that simultaneous polytherapy with ASMs improves OPNA-induced seizure outcomes.

Neurology International doi: 10.3390/neurolint18080145

Authors: Adam M. Abdallah Atef F. Hulliel Bayan Maraqa Mouness Obeidat

Background: Primary intra-axial cerebral schwannomas are exceptionally rare benign tumors that arise within the brain parenchyma without any association with cranial nerves. Their nonspecific clinical and radiological features frequently mimic high-grade gliomas, making preoperative diagnosis challenging. Case Presentation: We report the case of a 17-year-old male who presented with recent-onset right-sided visual disturbance and bilateral early papilledema. Magnetic resonance imaging demonstrated a lobulated, contrast-enhancing left occipitoparietal intra-axial mass with restricted diffusion, hyperperfusion, extensive vasogenic edema, and adjacent calvarial remodeling, raising suspicion for glioblastoma, gliosarcoma, or pleomorphic xanthoastrocytoma. The patient underwent gross-total resection through a left occipital craniotomy. Histopathological examination revealed a well-circumscribed cellular spindle-cell neoplasm with alternating hypercellular and hypocellular areas, perivascular hyalinization, and an absence of mitotic activity or necrosis. Immunohistochemistry demonstrated diffuse positivity for S100 and SOX10, negative Olig2 staining, retained INI-1 expression, and a low Ki-67 proliferation index of approximately 5%, establishing the diagnosis of a WHO grade 1 cellular schwannoma. Conclusions: Intra-axial cerebral schwannoma should be considered in the differential diagnosis of enhancing supratentorial brain lesions in children and adolescents, particularly when imaging suggests a high-grade glioma. Definitive diagnosis relies on histopathological and immunohistochemical evaluation. Gross-total resection is associated with excellent outcomes and durable disease control, although continued radiological surveillance remains advisable given the rarity of the condition.

Neurology International doi: 10.3390/neurolint18080144

Authors: Ahmed I. Anwar Abdul-rahman A. Hegazi Hamsa Priya Bhuchakra Joshua R. Nelson Ty L. Birdsong Cy J. Fontenot Majed Zeibo Moiz M. Fazal-ur-Rehman Harrison P. Bieber Claudia J. Spring Joshua L. Smith Ibraheem A. Hachem Taranjit Singh M. Farris Sawaya Kevin S. Murnane Alan D. Kaye

Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington’s disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood–brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington’s disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy.

Neurology International doi: 10.3390/neurolint18080143

Authors: M-Isabel Eraso Angela Carolina-Rosero Alma-Fuentes Melissa-Luque Maria Angelica-Coronel Luis Fontanilla Juan Camilo Rodriguez Narledys Bravo Nunez

Introduction: Stiff-Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle rigidity and painful spasms, primarily affecting axial and proximal musculature. Its diagnosis can be challenging due to clinical overlap with other neurological conditions such as spasticity, dystonia, or functional movement disorders. The detection of antibodies against glutamic acid decarboxylase (anti-GAD) is a key biomarker that supports diagnosis. Methods: Two clinical cases of patients with manifestations consistent with classic SPS are described, and were evaluated in a specialized neurology service. Both patients underwent detailed clinical assessment, complementary studies, and serum testing for anti-GAD antibodies. Results: Both patients presented with progressive rigidity and fluctuating muscle spasms, predominantly involving axial musculature. After an extensive diagnostic workup, elevated anti-GAD antibody titers were documented in both cases, confirming the diagnosis of classic SPS. Treatment with medications enhancing GABAergic neurotransmission was associated with significant clinical improvement, evidenced by reduced rigidity and the decreased frequency of spasms. Conclusions: These cases highlight the importance of considering SPS in the differential diagnosis of progressive rigidity syndromes. Identification of anti-GAD antibodies is essential for diagnostic confirmation, and treatment that aims to enhance GABAergic neurotransmission can significantly improve symptoms and patient functionality.

Neurology International doi: 10.3390/neurolint18080142

Authors: José Bel-Lacoma Ángela Aguilera-Rubio Roberto Cano-de-la-Cuerda

Background: Virtual reality (VR) is increasingly being explored as a tool for upper limb (UL) assessment in adults with neurological disorders. This review synthesizes the available evidence on VR-based UL assessments by analyzing their psychometric properties and potential role in clinical and research settings. Methods: This systematic review followed the Guideline for reporting systematic reviews of outcome measurement instruments (PRISMA-COSMIN) and was prospectively registered in PROSPERO. Data extraction was independently performed by two reviewers, with disagreements resolved by consensus or a third reviewer. Psychometric evidence was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, including risk of bias assessment, evaluation and synthesis of measurement properties, and evidence grading according to GRADE. Additionally, the clinical application context of each VR assessment was examined, and a strengths, weaknesses, opportunities and threats analysis was conducted to explore factors affecting implementation and future development in neurorehabilitation. Results: Twenty VR-based UL assessments were identified. VR-Box and Blocks Test represented the largest body of evidence and was the only assessment implemented across all immersion levels, with promising findings in both stroke and Parkinson’s disease populations (Grade B recommendation). Immersive Action Research Arm Test demonstrated the strongest psychometric profile among the stroke sample (Grade B recommendation). Additionally, the Virtual Occupational Therapy Assistant and SaeboVR® incorporated the most ecologically valid tasks, reflecting activities closer to daily life performance. Test–retest reliability and construct validity were the most frequently evaluated measurement properties. Conclusions: VR-based assessments represent promising tools for UL assessment. However, despite most systems receiving a Grade B recommendation, the supporting evidence remained low or very low certainty due to methodological shortcomings and incomplete psychometric evaluation. Therefore, more rigorous and methodologically robust research is needed to strengthen the evidence supporting their implementation in clinical practice as a complementary tool for UL assessment.

Neurology International doi: 10.3390/neurolint18080141

Authors: Narayanaswamy Venketasubramanian Tsong-Hai Lee Hou Chang Chiu Liang Guo Christopher Li Hsian Chen

Background: Post-stroke recovery varies widely, and pharmacological options to enhance rehabilitation outcomes remain limited. MLC601/MLC901 (NeuroAiD), a natural neurorestorative product, has been evaluated as an adjunct to standard care to improve functional and motor recovery after ischaemic stroke. This systematic review and meta-analysis assessed its efficacy using validated outcome measures. Methods: A systematic PubMed search identified randomised controlled trials comparing MLC601/MLC901 with placebo or active comparators in adults with ischaemic stroke. Functional outcomes included modified Rankin Scale (mRS), Barthel Index (BI), and Diagnostic Therapeutic Effects of Apoplexy (DTER) item 8 scores. Motor outcomes included Fugl–Meyer Assessment (FMA), DTER motor items, and National Institutes of Health Stroke Scale (NIHSS) motor scores. Data were pooled using fixed- and random-effects models. Odds ratios (ORs) and standardised mean differences (SMDs) were calculated. Risk of bias was assessed using the Cochrane RoB 1.0 tool. Results: Six publications reporting seven randomised clinical studies were included in the meta-analysis. Of the 7 studies, 5 were assessed as having a low risk of bias, while 2 were assessed as having an unclear risk. Altogether, 1535 participants for functional outcomes and 1774 for motor outcomes were analysed. Functional recovery significantly favoured MLC601/MLC901 at 1 month (OR 2.61; p = 0.004), 6 months (OR 1.38; p = 0.002), 12 months (OR 1.33; p = 0.03), and end-of-study (OR 1.40; p = 0.007), with benefits persisting up to 24 months. Motor recovery was assessed at months 1, 2 and 3 and at the end of the study. It also improved consistently over time, with the greatest effects during the first two months. Benefits were most evident in patients with moderately severe stroke (NIHSS 8–14). Clinical studies consistently indicate that NeuroAiD is safe and well-tolerated as an adjunct to standard ischaemic stroke care. Conclusions: MLC601/MLC901 is associated with improved functional independence and motor recovery after ischaemic stroke. Benefits appear within 1 month and may persist for up to 2 years, supporting early use alongside rehabilitation to optimise recovery.

Neurology International doi: 10.3390/neurolint18070140

Authors: Veljko Rabasovic Milan Radovanovic Milan Jovanovic Vladislav Glusac Nenad Stojiljkovic Varun Jain Natasa Radovanovic Bojana Milekic Charles W. Nordstrom Igor Dumic

Background: Influenza-associated encephalopathy, encephalitis, and acute necrotizing encephalopathy (ANE) are rare but potentially life-threatening neurological complications of influenza. Adult cases remain poorly characterized because the available literature is largely limited to isolated case reports and small case series. Methods: A PRISMA-guided scoping review of the MEDLINE database was conducted through 31 May 2026. Published adult cases of influenza-associated encephalopathy, encephalitis, and ANE were identified and analyzed for demographic characteristics, clinical presentation, neuroimaging findings, treatment, and outcomes. Results: Eighty-three adult cases reported between 1958 and 2026 were included. The mean age was 45.6 ± 17.8 years, and 57.8% were male. Two-thirds did not have any underlying comorbidities. Neurological symptoms developed a mean of 4.6 days after influenza onset, with influenza A accounting for 80.7% of infections. Fever (91.6%), altered mental status (86.7%), and seizures (36.1%) were the most common manifestations. Encephalitis was the predominant presentation (44.5%), followed by encephalopathy (31.3%) and ANE (24.1%). MRI most frequently demonstrated cerebral hemispheric lesions (53.0%) and bilateral thalamic involvement (36.4%), while EEG abnormalities were reported in 69.6% of patients. Overall mortality was 22.9%, highest among patients with ANE (45.0%). Among survivors, 28.9% experienced persistent neurological sequelae. Conclusions: Influenza-associated encephalopathy, encephalitis, and ANE are rare in adults but are associated with substantial morbidity and mortality. This review represents the largest adult cohort reported to date and provides important insights into the clinical spectrum, neurodiagnostic findings, and outcomes of these uncommon complications. This review highlights significant gaps in knowledge and the need for collaborative multicenter studies to improve the diagnosis, treatment, and outcome of these severe complications of influenza infection.

Neurology International doi: 10.3390/neurolint18070139

Authors: Chih-Wei Zeng

Neurodegenerative diseases represent a major and growing global health burden. Although these disorders are often clinically defined by symptoms and affected brain regions, many are mechanistically linked to abnormal protein accumulation, misfolding, impaired proteostasis, RNA dysregulation, mitochondrial dysfunction, and neuroinflammation. In this Perspective article, I discuss major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’s disease, prion diseases, spinocerebellar ataxias, and spinal muscular atrophy, through the lens of disease-associated proteins and experimental modeling. I argue that a protein-centered framework provides a useful approach for understanding disease mechanisms and selecting transgenic mouse models, while recognizing that aging, cellular context, neuroinflammation, mitochondrial dysfunction, vascular dysfunction, and other disease modifiers also shape neurodegeneration. Transgenic and genetically engineered mouse models have been essential for dissecting the pathogenic roles of amyloid-β, tau, α-synuclein, TDP-43, SOD1, FUS, C9ORF72-associated dipeptide repeat proteins, mutant huntingtin, prion protein, ataxins, and SMN deficiency. However, these models have important limitations, including artificial overexpression, familial mutation bias, species differences, and incomplete representation of aging-related sporadic diseases. Rather than seeking a single “best” model, a more productive strategy is to adopt model portfolios tailored to specific biological questions and to integrate mouse studies with human cellular models, postmortem tissue, omics approaches, and biomarker-based validation. Such an approach may improve mechanistic insight, strengthen translational relevance, and enhance the predictive value of preclinical neurodegenerative disease research.

Neurology International doi: 10.3390/neurolint18070138

Authors: Manal Aljuhani Azhaar Ashraf Abdullah Alqarni Mohammed S. Alshuhri Essam Mohammed Alkhybari Amani Alharbi Alanoud Almudayni Fatmah Jamal Alablani Azhar Akhmimi Ahmad A. Alhulail

Background: The role of cerebrospinal fluid (CSF) transforming growth factor β (TGF-β) isoforms in Alzheimer’s disease (AD) remains unclear. We examined associations of CSF TGF-β1, TGF-β2, and TGF-β3 with AD biomarkers, neurodegeneration, cognition, and clinical progression. Methods: In 294 ADNI participants with baseline CSF TGF-β measurements, adjusted regression, and mixed-effect models were used to evaluate associations with CSF biomarkers, neuroimaging, cognitive outcomes, and conversion. False-discovery-rate correction was applied. Results: Higher baseline TGF-β1 was associated with higher CSF total tau (β = 52.68 pg/mL per 1 SD increase; q < 0.001) and p-tau (β = 5.68 pg/mL; q < 0.001). Higher TGF-β2 was associated with faster hippocampal volume loss (β = −45.42 mm3/year; q < 0.001). No isoform was robustly associated with FDG-PET decline, cognitive decline, clinical conversion, or time to conversion. Conclusions: CSF TGF-β1 and TGF-β2 show distinct associations with tau-related pathology and hippocampal neurodegeneration, respectively, but do not appear to be prognostic biomarkers of clinical progression in AD.

Neurology International doi: 10.3390/neurolint18070137

Authors: Ivan Vukašinović Bojana Zivkovic Zarko Nedeljkovic Mirko Micovic Masa Petrovic Lidija Stanic Aleksandra Nedeljkovic Tijana Nastasovic Mihailo Milićević Vladimir Bascarevic

Background/Objectives: Spinal dural arteriovenous fistulas (sDAVFs) are the most common spinal vascular malformation and a treatable cause of progressive myelopathy, yet diagnosis and optimal management remain challenging. This study presents a nine-year institutional experience using a multidisciplinary treatment algorithm that prioritizes endovascular embolization, with surgery reserved for unsuccessful or contraindicated cases. Methods: We retrospectively analyzed 15 patients treated between 2015 and 2023, all diagnosed by MRI and confirmed by digital subtraction angiography. Endovascular embolization was attempted as the initial treatment modality in all patients using contemporary liquid embolic agents. Results: Three patients (20%) subsequently required surgical disconnection following unsuccessful or incomplete embolization. Lesions ranged from Th5 to L5, and most patients presented with varying degrees of motor deficits, gait disturbance, paresthesias, or sphincter dysfunction. Neurological improvement occurred in all but one patient, and no treatment-related complications were observed. Prior embolization attempts aided intraoperative localization in surgically treated cases, facilitating precise fistula identification. Conclusions: These findings demonstrate the feasibility and favorable outcomes of a multidisciplinary, stepwise treatment strategy in this single-center experience. Endovascular embolization served as the initial treatment modality, while surgical disconnection provided an effective complementary option in selected cases where embolization was unsuccessful or incomplete.

Neurology International doi: 10.3390/neurolint18070136

Authors: Akira Tamagawa Masahiro Horiuchi Takenori Abe Shinichi Matsumoto Yohei Mukai Kunihiko Ikeguchi Tomoo Mano Masahito Mihara Kimiyoshi Arimura Kotaro Asanuma Kanako Kurihara Sonoko Misawa Ryosuke Miyamoto Noriko Nishikawa Yuzuru Sasaki Shohei Tateishi Yusaku Nakamura

Background: This prospective, multicenter, open-label, single-arm study (jRCT2031230690) evaluated the efficacy and safety of a tailored dosing strategy of incobotulinumtoxinA, including high doses (up to 500 U) and flexible injection intervals (as short as 6 weeks), in Japanese patients with cervical dystonia (CD). Methods: Of 30 enrolled patients, Group A included 27 patients with idiopathic CD for the primary evaluation of efficacy and safety, whereas Group B included 3 patients with tardive dyskinesia (cervical) or tardive CD for exploratory safety assessment. Patients received up to seven injection cycles of incobotulinumtoxinA (120–500 U) over 48 weeks, with minimum 6-week intervals. The primary endpoint, evaluated in Group A, was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score from baseline to Week 4 after the first injection. Results: Using a mixed model for repeated measures, the least squares mean ± standard error of the change was −11.0 ± 1.77 (95% confidence interval: −14.6, −7.3). The primary efficacy endpoint was achieved in Group A. Due to the small sample size (n = 3), efficacy in Group B was evaluated only for exploratory purposes, although safety findings were broadly consistent with those in Group A. The overall safety profile was consistent with previous studies. Across the study, the most common related adverse events were dysphagia (33.3%) and muscular weakness (22.2%) in Group A and dysphagia (33.3%) in Group B. All cases of dysphagia were mild to moderate in severity and transient, with no apparent dose- or injection interval-related trend observed. Conclusions: IncobotulinumtoxinA was associated with improvements in symptoms and manageable safety profile at high doses and flexible injection intervals in Japanese patients with CD. While these findings suggest a potential treatment option for individualized dose optimization, the absence of a control group and the exploratory nature of the assessment in Group B necessitate cautious interpretation.

Neurology International doi: 10.3390/neurolint18070135

Authors: José Guilherme Jasper Pickler Hercílio Fronza Junior Francis Rossetti Pedack Luisa Andrade Gabardo Gabriel Coelho Barros Suzana Bastos Batista Bruna Louise Silva Paulo Henrique Condeixa de França Rafael Roesler Karina Munhoz de Paula Alves Coelho

Introduction: A subependymal giant cell astrocytoma (SEGA) is a benign tumor typically associated with tuberous sclerosis complex (TSC), an autosomal dominant syndrome. Case report: The patient, a 15-year-old male, presented with headaches, nausea, and visual obscurations, consistent with increased intracranial pressure. Neuroimaging identified a mass in the anterior left lateral ventricle causing unilateral obstruction at the foramen of Monro. During microsurgery, smears showed a low-grade glial tumor with a biphasic mix of elongated astrocytes and large epithelioid-to-gemistocyte-like cells. Gross total resection was achieved. On permanent sections, a tumor with large polygonal, ganglioid, and gemistocytic-like cells was seen. Nuclear pleomorphism, a feature of SEGA, was present. On immunohistochemistry, the tumor was positive for glial fibrillary acidic protein (GFAP), S100, and CD34, and the cells also displayed nuclear staining for TTF-1. A diagnosis of SEGA in the absence of clinical features of TSC was established; however, definitive classification as sporadic remains limited by the lack of molecular data. Conclusions: This case highlights the importance of evaluating intraventricular masses through the integration of lineage-specific immunohistochemical panels to prevent misclassification of pleomorphic giant cells as high-grade gliomas.

Neurology International doi: 10.3390/neurolint18070134

Authors: Hisanao Akiyama Yasutaka Watanabe Takayuki Fukano Takahiro Shimizu Yoshihisa Yamano

Background/Objectives: Detecting covert paroxysmal atrial fibrillation (AF) in patients with suspected embolic stroke of undetermined source (ESUS) is important for secondary prevention. This study evaluated the feasibility, AF detection, and wearability of the hitoe® wearable electrocardiogram (ECG) monitoring system II, a Holter-type device recording continuously for up to 14 days. Methods: Between March 2022 and October 2023, 31 patients with suspected ESUS were enrolled. After excluding two cases, 29 patients (mean age 74.7 ± 17.3 years; 16 men) underwent ECG monitoring. Clinical outcomes were analyzed in 27 acute-phase patients and wearability in 24 questionnaire respondents. ECG recordings and questionnaire responses were analyzed descriptively, with between-group comparisons. Results: In 29 monitored patients, the mean recording duration was 12.4 ± 3.7 days, the ECG acquisition rate was 64.0 ± 23.4% (median 72.1%), and the mean analyzable duration was 8.1 ± 3.7 days. In the 27 acute-phase patients, covert paroxysmal AF was detected in 2 patients (7.4%), on days 1, 3, and 15 in one patient and on day 7 in the other. In AF-positive patients, the mean ectopic burden was 1.33% for supraventricular and 0.24% for ventricular activity. Wearability was favorable: 77.8% reported no interference with daily activities, none reported sleep disturbance, and 72.7% adapted within 1–4 days. Conclusions: The hitoe® wearable ECG monitoring system II enabled prolonged monitoring across inpatient and outpatient settings, detecting covert paroxysmal AF in 7.4% of acute-phase patients with suspected ESUS. These findings support garment-type wearable ECG monitoring as a non-invasive option for extended rhythm surveillance.

Neurology International doi: 10.3390/neurolint18070133

Authors: Floriana Cascone Gemma Gasparini Valeria Tiranti Ivano Di Meo

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare genetic movement disorders characterized by progressive neurological deterioration, dystonia, parkinsonism, spasticity, and abnormal iron deposition in the basal ganglia. Although iron accumulation is the shared neuroradiological hallmark, most NBIA genes do not directly regulate iron metabolism. Instead, major NBIA forms arise from disruption of distinct but converging cellular pathways, including coenzyme A (CoA) biosynthesis, lipid metabolism, mitochondrial function, and autophagy. This narrative review aims to examine the pathogenic mechanisms of major NBIA disorders, namely pantothenate kinase-associated neurodegeneration (PKAN), COASY protein-associated neurodegeneration (CoPAN), PLA2G6-associated neurodegeneration (PLAN), mitochondrial membrane protein-associated neurodegeneration (MPAN), and beta-propeller protein-associated neurodegeneration (BPAN), and how these insights are guiding therapeutic development. Preclinical strategies aimed at restoring CoA metabolism, improving mitochondrial function, limiting lipid peroxidation, modulating autophagy, or correcting the underlying genetic defect have shown encouraging results, although none have yet reached robust clinical validation. Clinical translation remains limited by disease rarity, clinical heterogeneity, absence of validated biomarkers, and preclinical models that only partially recapitulate human pathology. Advancing the field will depend on earlier molecular diagnosis, biomarkers capable of tracking disease stage, and trial designs suited to ultra-rare populations. NBIA thus offers a paradigm for how mechanistic classification of a genetically defined disease group can redirect therapeutic strategy away from a shared radiological feature and toward pathway-specific intervention.

Neurology International doi: 10.3390/neurolint18070132

Authors: Silviu Lunguț Suzana Turcu Cristiana Glavce

Headache is a frequent and clinically relevant symptom in patients undergoing cranial radiotherapy, most often reflecting treatment-induced structural and inflammatory changes such as cerebral edema or radiation-related brain injury. Differentiating secondary headache from primary disorders, particularly migraine, is essential for appropriate management. This review aims to examine the pathophysiological mechanisms underlying headache following cranial radiotherapy, evaluate current pharmacological and complementary treatment strategies and highlight key aspects of differential diagnosis with migraine. Unlike existing literature that focuses primarily on radiological findings of radiation injury, this review adopts a symptom-driven approach, reframing headache as a critical clinical gateway for the early detection of structural complications. A structured narrative review of the literature was conducted using PubMed/MEDLINE, Scopus and Google Scholar to identify studies published between 2020 and 2025, focusing on cerebral edema, radiation-related complications, therapeutic approaches and migraine. Relevant clinical trials, systematic reviews and guidelines were included. Cerebral edema consistently emerges as the main mechanism of acute and subacute post-radiotherapy headache, whereas late-onset symptoms are most often linked to radiation necrosis. Corticosteroids remain first-line therapy, while bevacizumab has demonstrated benefit in steroid-refractory cerebral edema and radiation necrosis through inhibition of vascular endothelial growth factor (VEGF), thereby reducing vascular permeability and attenuating peritumoral edema. Its use in the context of cranial radiotherapy requires careful consideration, as the safety of concomitant administration with radiation has not been formally established, and headache itself is among its recognized adverse effects. Evidence for complementary therapies, including Boswellia serrata and plant-based compounds, remains limited. Migraine constitutes a distinct neurovascular disorder requiring careful differentiation from secondary headache in oncological patients. The review emphasizes headache as a clinically relevant indicator of underlying structural complications rather than an isolated symptom. Post-radiotherapy headache should be interpreted as a manifestation of underlying structural pathology. Accurate etiological diagnosis and individualized management are essential. Further research is needed to refine treatment strategies and clarify the role of complementary therapies.

Neurology International doi: 10.3390/neurolint18070131

Authors: Rocío Llamas-Ramos Jorge Juan Alvarado-Omenat Daniel García-García Ismael Sanz-Esteban Juan Luis Sánchez-González J. Ignacio Serrano Inés Llamas-Ramos

Background: Central nervous system development is a rapid and highly plastic process during the first years of life. Tactile stimuli have been shown to induce cortical changes, but potential sex-related differences remain unexplored. This study aimed to investigate sex-specific differences in cortical activity and cerebral oxygenation in response to tactile stimulation via body massage. Methods: Four healthy full-term infants (two females and two males), all aged 11 weeks, were included in this prospective exploratory study. Each infant received a standardized 5 min massage protocol. Cortical activity and cerebral oxygenation were assessed using an 8-channel electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) before, during, and after the intervention, with a 5 min pre-intervention resting period used as the baseline. Results: EEG analysis focused on a single spectral band (4 Hz–30 Hz). This range was selected to capture the main cortical oscillations in infants, including theta, alpha, and beta activity, while delta activity below 4 Hz was partially excluded to reduce movement and physiological artifacts. Standard infant EEG bands were considered when defining this range. Data shows for the female subject an average PSD of −6.726 (± −4.075), and for the male subject, −12.594 (± −10.741). Although babies are of the same gestational age, they exhibited distinct basal cortical activity, which prevented comparisons from being made. Nevertheless, massage induced similar activity patterns in all subjects with increased cortical electrical activity in the left parietal region relative to baseline. fNIRS data showed that comparable HbO concentration patterns between participants were observed only during the second minute of recording. Relative to baseline, pre-intervention HbO responses displayed an opposite distribution, and the effects of the intervention differed by sex. The female participant exhibited a slight reduction in activation in the right hemisphere accompanied by a modest increase in the most ventral region of the left hemisphere. Conversely, the male participant showed an inverse response pattern, characterized by a marked increase in right hemispheric activation and a pronounced decrease in the left hemisphere during the intervention period. Conclusions: These preliminary observations suggest the presence of early variations in cortical processing that warrant further investigation in larger samples, although they cannot be considered conclusive. While baseline response patterns differed between participants, both showed increased left parietal activity during tactile stimulation. The inversion of HbO responses between the pre-intervention and intervention phases points to potential sex-related differences in hemodynamic trajectories. Nevertheless, these results remain preliminary, and larger, well-powered studies are required to determine whether these patterns reflect stable, sex-dependent developmental changes.

Neurology International doi: 10.3390/neurolint18070130

Authors: Kenta Tasaki Makoto Hara Hideto Nakajima

Objectives: Varicella zoster virus (VZV) meningitis is a complication of herpes zoster that causes high rates of residual symptoms. However, prognostic factors and optimal management strategies remain unclear. This study investigated factors affecting functional outcomes, age-related differences, and the impact of prior oral antiviral therapy in VZV meningitis. Methods: This retrospective observational study enrolled patients admitted for aseptic meningitis between 2013 and 2022. The primary outcome was residual symptoms at discharge, defined as a ≥1-point increase in the modified Rankin Scale (mRS) from baseline. Multiple logistic regression identified independent risk factors. Results: Among 176 patients with aseptic meningitis, 60 (34.1%) had VZV meningitis. Patients with VZV meningitis had higher rates of residual symptoms (43.3% vs. 12.9%, p < 0.001). Independent predictors of residual symptoms included delayed intravenous acyclovir initiation (odds ratio [OR] = 1.303, 95% confidence interval [CI] = 1.060–1.601, p = 0.012), corresponding to a 30.3% increase in the odds of residual symptoms for each additional day before treatment initiation, and pre-onset mRS (OR = 2.352, 95% CI = 1.056–5.237, p = 0.036). Patients ≥ 50 years old displayed lower rates of headache (75.0% vs. 96.9%, p = 0.020), neck stiffness (25.0% vs. 62.5%, p = 0.005), and CSF pleocytosis (56/μL vs. 142/μL, p = 0.023). Prior oral antiviral therapy was not associated with a rate of residual symptoms (p = 0.795). Conclusions: Delayed initiation of intravenous acyclovir was independently associated with residual symptoms at discharge, whereas older patients often presented with atypical clinical features, requiring heightened clinical suspicion. Given the lack of observed benefit associated with prior oral antiviral therapy, prompt initiation of intravenous acyclovir should be considered when VZV meningitis is suspected.

Neurology International doi: 10.3390/neurolint18070129

Authors: Petar Vasilev Ekaterina Viteva Anna Todeva-Radneva Antonia Yaneva Dora Zlatareva Tina Zdravkova Sevdalina Kandilarova

Background/Objectives: Epilepsy is a chronic brain disease characterized by recurrent epileptic seizures. It affects roughly 50 million people worldwide and around one third of the patients have drug-resistant epilepsy (DRE). The current study aimed to find differences in the whole-brain functional connectivity (FC) in patients with DRE compared to patients with well-controlled epilepsy (WCE) and healthy controls (HCs). Methods: This explorative, cross-sectional study included 92 participants (nDRE = 30; nWCE = 30; nHC = 32) who underwent resting-state functional magnetic resonance imaging (fMRI). The CONN Toolbox was used to process and analyze the FC changes among the three groups. Results: There was a statistically significant increase of the FC between the left lateral prefrontal cortex, left inferior temporal gyrus (temporo-occipital), left lobules IV and V of the cerebellum and multiple cortical and subcortical structures in patients with DRE as opposed to WCE and HC. On the other hand, decreased FC was observed between three seeds (the posterior cingulate cortex, precuneus cortex, the right planum polare) and different frontal, temporal and occipital regions. Interestingly, the right nucleus accumbens (r_NAc) showed increased FC with the inferior frontal gyrus in DRE compared to WCE, whereas the r_NAc-left precentral gyrus FC was reduced in DRE as opposed to HC. Conclusions: The acquired information offers valuable insights into the neuronal networks associated with DRE. These data could be used for advancing diagnostic accuracy and future therapeutic strategies.

Neurology International doi: 10.3390/neurolint18070128

Authors: Alejandro Bruna-Mejias Loreto Paez-Allendes Valentina Perez-Lira Diego Santander-Chavez Mathis Miranda-Schoen Juan José Valenzuela-Fuenzalida María P. Moya Gustavo Oyanedel-Amaro Gloria Cifuentes-Suazo Mathias Orellana-Donoso Juan J. Cabezas-Salgado Cristopher Blackwood-Espinoza Juan Sanchis-Gimeno

Purpose: Meningo-ophthalmic and orbitomeningeal arterial communications comprise route-specific relationships between the middle meningeal artery (MMA) and the ophthalmic or orbital arterial system. Their recognition is relevant to middle meningeal artery embolization because orbital or ophthalmic collateral pathways may create routes for non-target embolization. This systematic review aimed to synthesize the prevalence and anatomical patterns of these communications, using quantitative pooling only where the anatomical definition and denominator were sufficiently coherent. Methods: This systematic review and meta-analysis were conducted according to PRISMA 2020 principles and registered in PROSPERO (CRD420261361050). Eligible studies were original human cadaveric anatomical, angiographic, or radiological investigations reporting MMA-ophthalmic or MMA-orbital arterial relationships. After the closure of the full-text retrieval audit, studies and extracted rows were audited by anatomical family, unit of analysis, numerator, denominator, and independence. No global pooled prevalence was calculated across anatomical families. When family-specific pooling was methodologically defensible, proportions were synthesized using logit transformation, restricted maximum likelihood random-effects models, and Hartung-Knapp confidence intervals. Results: Database searches identified 558 records. After removal of 228 duplicates, 330 records were screened, and 285 were excluded by title and abstract. Forty-five reports were sought for retrieval; 10 were not retrieved or were not available as assessable full-text reports after retrieval auditing. Thirty-five full-text reports were assessed; thirteen were excluded for reasons, and three were duplicate reports at the full-text stage. Nineteen studies were included in the qualitative synthesis, and 12 contributed independent data to the final R-ready matrix. MMA arising from the ophthalmic artery was uncommon, with a pooled prevalence of 0.03 (95% CI 0.01 to 0.13; I2 = 75.9%). After excluding the clinically selected chronic subdural hematoma subgroup, the estimate was 0.02 (95% CI 0.01 to 0.06; I2 = 7.7%). The meningolacrimal/lacrimal-MMA route yielded an exploratory pooled proportion of 0.45 (95% CI 0.09 to 0.86; I2 = 95.9%), with substantial anatomical and methodological heterogeneity. Conclusions: The available evidence supports route-specific synthesis rather than a single global prevalence estimate. MMA arising from the ophthalmic artery appears uncommon but procedurally important; however, this estimate should be interpreted as a route-specific estimate across eligible angiographic/anatomical series rather than as a universal anatomical prevalence. Meningolacrimal and lacrimal-MMA routes are frequently described, but their prevalence remains difficult to generalize because detection methods, populations, and denominators differ across studies. Future anatomical and angiographic reports should standardize route definitions, laterality, unit of analysis, and denominator reporting to improve prevalence estimation and procedural safety interpretation.

Neurology International doi: 10.3390/neurolint18070127

Authors: María Pérez-Montalbán Encarna García-Domínguez Manuel Pabón-Carrasco Ángel Oliva-Pascual-Vaca

Background: Autonomic dysfunction is increasingly recognized as a key mechanism in disorders involving the brain–gut axis and gastrointestinal symptom generation. Transcutaneous vagus nerve stimulation (tVNS) is a noninvasive neuromodulatory technique investigated for its potential effects on autonomic regulation. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines, with protocol registration in PROSPERO. Randomized controlled trials (RCTs) investigating auricular or cervical tVNS in patients with visceral disorders were included. Continuous outcomes were pooled using mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). When multiple publications originated from the same trial population, only independent datasets were considered for quantitative synthesis to avoid double-counting participants. Risk of bias was assessed using the PEDro scale and certainty of evidence with the GRADE approach. Results: Seven RCTs met the inclusion criteria. tVNS demonstrated a small but statistically significant improvement in gastrointestinal symptoms based on change-from-baseline GSRS scores (MD −0.19; 95% CI −0.29 to −0.09; p < 0.001; I2 = 0%). Although statistically significant, the magnitude of this effect was modest, and its clinical relevance remains uncertain. No significant effects were observed on cardiac vagal tone (SMD 0.19; 95% CI −0.53 to 0.90; p = 0.61; I2 = 73%) or systolic blood pressure (MD −1.24 mmHg; 95% CI −6.69 to 4.21; p = 0.66; I2 = 0%). Evidence regarding cardiac autonomic neuropathy (CAN) was limited to a single independent randomized controlled trial, which found no significant differences between tVNS and sham stimulation. Conclusions: tVNS provides modest statistically significant improvements in gastrointestinal symptoms, supporting its role as a symptomatic neuromodulatory intervention. However, the available evidence for this outcome was based on only two studies, and the clinical relevance of the observed effect remains uncertain. No statistically significant pooled effects were observed for the cardiovascular autonomic markers assessed in this review. Evidence regarding CAN was limited to a single independent study. Therefore, the available evidence remains limited and heterogeneous, and further high-quality randomized controlled trials are warranted.

Neurology International doi: 10.3390/neurolint18070126

Authors: Kamil Krystkiewicz Aleksander Kowal Magdalena Krystkiewicz-Orzechowska Filip Arczewski Karol Dziedzic Marcin Tosik

Introduction/Objectives: Wall irregularity is a known risk factor in the evaluation of intracranial aneurysms, but the prognostic value of its subtypes remains unclear. Materials and methods: In this retrospective single-center cross-sectional study (2023–2025), we reviewed consecutive adult patients with intracranial aneurysms. Morphology was classified as daughter sac, multilobulated, or complex irregularity. We compared rupture status and calculated PHASES, ELAPSS, and UIATS scores. Principal Component Analysis (PCA), and logistic and linear regression were applied. Results: A total of 180 patients with 180 index aneurysms were included; mean age was 67.2 ± 12.1 years, and 72.2% were women. Overall, 43.3% of aneurysms were irregular, specifically: daughter sac (25.0%), multilobulated (36.1%), and complex irregularity (11.1%). SAH occurred in 40 patients (22.2%). Ruptured aneurysms had larger maximum diameter, size ratio, and aspect ratio (all p < 0.0001), plus higher 5-year PHASES (p = 0.0091) and ELAPSS growth scores (p < 0.0001). PCA identified three clusters with differing 5-year rupture risks; Cluster 3 had the highest risk (5.71 ± 5.25%) and was characterized by a higher proportion of daughter sac and multilobulated morphology (p = 1.65 × 10−7 and 8.80 × 10−16). Linear models showed each irregular subtype was associated with significantly larger aneurysm size. Conclusions: Irregular wall patterns were common and associated with larger aneurysm dimensions and higher risk scores. These findings support further investigation of refined morphological descriptors in rupture risk stratification.

Neurology International doi: 10.3390/neurolint18070124

Authors: Anas Z. Nourelden Fen Bao Abigail Biddix Nidhi Patel Mawadda Abdelhai Basil Memon Vivian Truong Zaima Liaquat Carla Santiago-Martinez Yongsheng Chen Anza B. Memon

Background/Objectives: Multiple sclerosis (MS) can cause neurodegeneration leading to accelerated brain atrophy. Brain-predicted age (BA) is an emerging neuroimaging biomarker for neurodegeneration but remains underexplored in MS. This study examines the pathophysiological substrates associated with the brain age gap in MS compared with healthy controls (HCs) through a combination of volumetric, spectroscopic, and diffusion imaging. Methods: This retrospective cross-sectional study included 33 HCs and 124 MS patients. Participants underwent 3T MRI including 3D-T1, MR spectroscopy, magnetization transfer, and diffusion imaging. BA and volumes were estimated from T1-weighted scans using brainageR. Metabolic integrity (total N-acetylaspartate to total creatine ratio, tNAA/tCr) and microstructural damage (magnetization transfer ratio [MTR], fractional anisotropy [FA]) were evaluated independently in normal-appearing tissues. Multivariate linear regression assessed MS diagnosis as an independent predictor of BA metrics, controlling for age, sex, and race. Results: MS patients showed significantly higher predicted brain age (53.3 vs. 31.8 years) and a markedly larger age gap (10.2 vs. −0.1 years) compared to HCs. Beyond macroscopic volume loss, accelerated aging paralleled profound subclinical degradation, including lower neuronal integrity (tNAA/tCr: 2.0 vs. 2.4) and widespread microstructural damage, evidenced by reduced MTR and FA across both normal-appearing gray and white matter. Linear regression confirmed MS diagnosis as an independent predictor of both BA and Age Gap (15.09 and 13.50 years) after adjusting for confounders. Conclusions: MS patients exhibit accelerated biological brain aging, characterized by a significant age gap and concurrent tissue volume loss. The brain age gap in MS extends beyond macroscopic atrophy, capturing underlying subclinical metabolic failure and widespread microstructural degradation in normal-appearing tissues. This positions BA as a robust, multi-dimensional proxy for neuroaxonal pathology.

Neurology International doi: 10.3390/neurolint18070125

Authors: Domenico Plantone Carlo Manco Delia Righi Stefania Lago Alessio Rocco Sangiorgio Valentina Schino Matteo Pardini Angela Stufano Guglielmo Lucchese

Background/Objectives: Herpesviridae have been increasingly investigated as possible contributors to Alzheimer’s disease (AD) because of their neurotropism, lifelong latency, and capacity to modulate inflammatory and amyloid-related pathways Methods: This structured narrative review, based on a systematic literature search, examined original studies published between December 2020 and December 2025 on the association between human herpesviridae and AD. Searches were conducted in PubMed, Web of Science, and Scopus using a PRISMA-informed screening framework. Results: The available evidence was heterogeneous across viruses and study designs. HSV-1 emerged as the most consistently implicated virus, supported by epidemiological, biomarker, neuroimaging, and experimental studies, although contradictory findings were also reported. VZV was mainly associated with AD through vascular, inflammatory, and vaccination-related evidence, with several studies suggesting lower dementia risk after zoster vaccination. CMV, EBV, and HHV-6 showed biologically plausible but less consistent associations, whereas HHV-7 and HHV-8 were supported only by limited or indirect evidence. Across studies, the proposed mechanisms included chronic neuroinflammation, vascular injury, amyloid and tau dysregulation, host immune responses, and cumulative infectious burden. Conclusions: Overall, the literature suggests that the relationship between herpesviridae and AD is not uniform and that HSV-1 appears to be the most relevant candidate. However, methodological heterogeneity, possible reverse causation, and unequal study intensity across viruses limit firm conclusions. More robust longitudinal and subtype-specific studies are needed to clarify causal relevance.

Neurology International doi: 10.3390/neurolint18070123

Authors: Kamal Smimih Chaima Azzouhri Bilal El-Mansoury Ahmed Draoui Hasna Lahouaoui Abdelali Bitar Mohamed Merzouki Omar El Hiba

Prenatal alcohol exposure (PAE) is recognized as a major public health concern due to its profound and lasting effects on the central nervous system (CNS) and its ability to induce fetal alcohol spectrum disorders (FASD), which encompass a wide range of cognitive, behavioural, and neuropsychiatric disorders that persist throughout life. Experimental and clinical studies have identified several mechanisms underlying ethanol impairing brain development, including apoptosis, oxidative stress, disruption of morphogen and growth factor signalling pathways, impaired neuronal proliferation and migration, neurotransmitter systems’ dysfunction, glial cells damage associated with deficient myelination, vascular and blood–brain barrier (BBB) alterations, and lasting epigenetic reprogramming. However, to date no widely accepted integrative framework explaining how these impairments underline the heterogeneous phenotype observed in FASD is available. The present brings together developmental neurobiology and computational neuroscience to conceptualize PAE as a disorder of emerging neural and functional architecture. Here, we summarize the pharmacokinetics of ethanol in pregnancy, critical windows of vulnerability, and the classical pathways of alcohol teratogenesis affecting neuronal survival, migration, synaptogenesis, myelination, and gene regulation. We have also reviewed MRI, diffusion imaging, and EEG/MEG evidence showing altered brain volumes, white matter microstructure, functional connectivity, and network organization in individuals with PAE. Finally, we propose a systems-level model that conceptualizes PAE as a disorder of emerging neuro-computational architecture, in which ethanol-induced cellular and molecular perturbations collectively alter the building blocks and self-organization rules of brain network assembly.

Neurology International doi: 10.3390/neurolint18070122

Authors: Rayya Ali S. Almarwani Anas Muslih B. Alkalbi Juan Toro Perez

Background: Eye-closure sensitivity (ECS) is a rare reflex epilepsy phenomenon characterized by epileptiform discharges on electroencephalogram (EEG), triggered by eye closure. It has been reported in all genetic generalized epilepsies (GGEs), particularly in adolescents and adults. However, pediatric cases remain uncommon in the literature. Case Presentation: We report a 10-year-old previously healthy girl who presented with recurrent generalized tonic–clonic seizures beginning at age nine. Seizures occurred every few months without identifiable triggers, lasting 1–2 min with complete loss of consciousness, limb stiffening, rhythmic jerking, and upward eye deviation. Her developmental history was unremarkable, with no family history of epilepsy or febrile seizures. Neurological examination was normal. Initial EEG revealed intermittent generalized spike-and-wave and polyspike-and-wave discharges at 3 Hz (range 2–4 Hz), triggered by eye closure, consistent with ECS. These discharges occurred immediately following both spontaneous and instructed eye closure, were more prominent during drowsiness, and resolved upon eye opening. The patient remained alert during these subclinical events. No photosensitivity or hyperventilation response was observed. Brain magnetic resonance imaging was normal. The patient’s electroclinical findings were most consistent with a GGE phenotype with prominent ECS. She was treated with levetiracetam and has remained seizure-free for approximately 1.5 years to date. Conclusions: This case demonstrates that ECS can present in pediatric patients with GGE primarily manifested as generalized tonic–clonic seizures. EEG evaluation should include repeated eye-open/close maneuvers to unmask ECS, particularly in children with suspected generalized seizures.

Neurology International doi: 10.3390/neurolint18060121

Authors: József Janszky József Janszky Réka Horváth

Objective: Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy often presents as chronic focal epilepsy, usually with temporal lobe predominance, marked drug resistance, and inconsistent response to first-line immunotherapy. We assembled a large, harmonized, and literature-derived patient-level cohort to examine whether immunotherapy timing and regimen composition were associated with seizure outcome and to identify clinically meaningful prognostic signals. Methods: We performed a literature-derived patient-level analysis of 375 unique published cases linked to 132 contributory source publications from an audited full-text register of 166 reviewed studies. Descriptive analyses used the whole cohort. Treatment-response analyses assessed seizure outcome at the first evaluable post-immunotherapy assessment and at the last follow-up. Good seizure outcome was defined as seizure freedom and/or ≥50% seizure reduction. The primary timing comparison contrasted early treatment, defined as immunotherapy within 6 months of symptom onset, with late treatment, defined as immunotherapy after more than 12 months; four cases treated in the intermediate >6 to ≤12 month window were retained for descriptive timing summaries but excluded from the primary comparison. Statistical testing used the Fisher exact, Chi-square, Mann–Whitney U, and prespecified clustered logistic sensitivity analyses where appropriate. Results: The pooled phenotype was predominantly female, usually temporal-lobe-based, and frequently drug-resistant, with common autoimmune comorbidity and heterogeneous MRI abnormalities. Among timing-evaluable treated cases, earlier immunotherapy showed a class-specific, exploratory signal rather than a uniform regimen-independent effect. In rituximab/CD20-directed regimens, early treatment was associated with a higher rate of good seizure outcome than late treatment at both the first post-immunotherapy assessment and last follow-up (93.8% vs. 50.0%; risk difference [RD]: 43.8 percentage points; 95% CI: 7.7 to 72.7). A similar pattern was observed in the broader escalation group (94.4% vs. 55.6%; RD: 38.9 percentage points; 95% CI: 6.3 to 68.1). By contrast, steroid-containing regimens showed no clear early-versus-late advantage (84.6% vs. 88.2%; RD: −3.6 percentage points; 95% CI: −18.4 to 20.1). Shorter epilepsy duration before immunotherapy and absence of established drug resistance were the most clinically meaningful favorable baseline features. Significance: In GAD65 antibody-associated epilepsy, the therapeutic window may be most relevant for escalation strategies rather than for steroid-containing first-line regimens. However, these class-specific findings are exploratory and hypothesis-generating. They derive from non-randomized, literature-derived data and may reflect treatment intensity, center practice, publication era, and confounding by indication rather than isolated regimen superiority. Prospective collaborative registries with standardized longitudinal seizure outcome measures are needed to validate these observations.

Neurology International doi: 10.3390/neurolint18060120

Authors: Patricia Patricia Anak Agung Ayu Putri Laksmidewi Kumara Tini Anak Agung Ayu Meidiary Ni Made Susilawathi Ida Ayu Sri Wijayanti

Background: Cognitive impairment is a common complication after ischemic stroke and affects patients’ quality of life. Elevated glial fibrillary acidic protein (GFAP) and low vitamin D levels may contribute to neuroinflammation and impaired neuroplasticity, but their association with post-stroke cognitive impairment remains unclear. This study aimed to determine whether high serum GFAP and low vitamin D levels are risk factors for cognitive impairment in ischemic stroke patients. Methods: A prospective cohort study was conducted in patients with acute ischemic stroke. Serum GFAP and vitamin D levels were measured on the third day after stroke onset using an enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed two weeks after stroke onset using the Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina). Data were analyzed using the chi-square test and multivariate logistic regression. Results: Seventy-six subjects were included in this study, of which 55 (72.4%) developed cognitive impairment. High serum GFAP (≥1.885 ng/mL) (RR = 1.755; 95% CI: 1.252–2.459; p = 0.001) and low vitamin D levels (<16.185 ng/mL) (RR = 1.773; 95% CI: 1.234–2.547; p = 0.001) were both associated with cognitive impairment. Multivariate analysis showed that high GFAP (AOR = 10.039; 95% CI: 2.484–40.569; p = 0.001) and low vitamin D levels (AOR = 6.640; 95% CI: 1.798–24.518; p = 0.005) were independent risk factors. Conclusions: Elevated serum GFAP and low vitamin D levels were independently associated with cognitive impairment after ischemic stroke and may serve as potential biomarkers for early risk stratification.

Neurology International doi: 10.3390/neurolint18060119

Authors: Faraz Behzadi Thomas C. Varkey Shan Rizvi Zana Alattar Chase Seiter Sydni Martinez Allison J. Tompeck Khalid Alsherbini

Introduction: Moderate-to-severe TBI (msTBI) disproportionately affects younger populations with high mortality and severe morbidity amongst survivors. A higher hemoglobin level has been suggested to improve oxygen delivery to the injured brain, and recent randomized trials revealed that more liberal hemoglobin (Hgb) transfusion thresholds may improve 6-month neurologic functional outcomes measured by Glasgow Outcome Scale Extended (GOS-E). This article aims to perform a comprehensive meta-analysis of functional neurologic outcomes and early mortality in msTBI patients with liberal (8 g/dL) versus restrictive (7 g/dL) hemoglobin (Hgb) transfusion thresholds. Methods: The Medline, Embase, and Cochrane databases were searched for primary literature concerned with msTBI and early Hgb transfusion thresholds, from inception to October 2025. Risk of bias was assessed for all selected articles. With a common-effect model, we estimated the pooled odds ratio of the primary outcome (6-month unfavorable outcome defined as GOS-E ≤ 4 or 5) and the secondary outcome (30-day mortality) for liberal versus restrictive Hgb transfusion thresholds. Results: After reviewing 484 articles, 12 met the inclusion criteria with 8 reporting 6-month functional neurological outcomes and 10 that reported 30-day mortality. After a direct comparison of 5208 cumulative patients, those with more liberal transfusion thresholds had a statistically significant reduction in unfavorable outcomes at 6 months (OR = 0.67; 95% CI [0.58–0.77]; p < 0.0001) compared to those with restrictive thresholds. Liberal transfusion thresholds showed no significant effect on 30-day mortality with the direct comparison of 4589 cumulative patients (OR = 0.93, 95% CI [0.78–1.11]). Conclusions: Higher Hgb transfusion thresholds in patients presenting with msTBI can improve functional outcomes at 6 months with a lack of significant effects on 30-day mortality.

Neurology International doi: 10.3390/neurolint18060118

Authors: Alexandra Evancho Jennifer Dawson Harrison C. Walker Christopher G. Ballmann William J. Tyler

Background: 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. Methods: 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. Results: 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. Conclusions: 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.