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.

Neurology International doi: 10.3390/neurolint18060117

Authors: Alice Tomaselli Antonina Luca Mario Lentini Jerome Rene Lechien Federico Mollame Alberto Caranti Claudio Vicini Matteo Lazzeroni Pasquale Capaccio Giannicola Iannella Valentin Favier Antonino Maniaci

Background/Objectives: Cognitive decline and dementia represent a growing global crisis, affecting over 57 million individuals worldwide, projected to exceed 150 million by 2050. The 2024 Lancet Commission identified hearing loss as the single largest modifiable dementia risk factor (~7% population-attributable fraction). Obstructive sleep apnea (OSA), affecting ~936 million adults, is an increasingly recognized contributor yet remains underdiagnosed, especially in low- and middle-income countries (LMICs). This review synthesizes evidence on the global burden of cognitive decline associated with both conditions, evaluates causality debates, and identifies research gaps. Methods: Following SANRA guidelines, a search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library through February 2026. Original studies, systematic reviews, meta-analyses, and WHO/GBD reports were included; editorials and non-English publications were excluded. After deduplication, 3847 records were screened, and 96 studies met the inclusion criteria. Results: OSA has been linked to cognitive decline through several plausible mechanisms, including intermittent hypoxia, sleep fragmentation, impaired glymphatic clearance, and amyloid-beta accumulation, though the directionality of these associations requires confirmation from longitudinal studies. Hearing loss contributes to cognitive load, social isolation, and cortical reorganization. Both conditions disproportionately affect LMICs, where access to diagnosis and treatment remains limited. CPAP and hearing rehabilitation show cognitive benefits when initiated early, though evidence for reversing established impairment remains limited. A synergistic interaction between the two conditions is biologically plausible but empirically underexplored. Conclusions: OSA and hearing loss are highly prevalent conditions associated with increased dementia risk, though the certainty of causal relationships and the magnitude of intervention effects differ between the two conditions and across the available evidence. Integrated screening and early intervention could yield substantial neuroprotective benefits in high-risk populations and LMICs. Future longitudinal studies should examine combined cognitive trajectories and optimal intervention timing.

Neurology International doi: 10.3390/neurolint18060116

Authors: Beatrice Dell’Acqua Carmelina Maria Costa Andrea Cerri Alessandro Francia Simone Vidale

Background and Purpose: Tenecteplase (TNK) within 4.5 h from symptom onset is not inferior to alteplase in treating ischemic stroke. In recent years, some randomized controlled trials (RCTs) have investigated the efficacy of extending the therapeutic window up to 24 h. This updated meta-analysis aims to synthesize the results of these RCTs comparing TNK to the best medical treatment (BMT) with or without endovascular thrombectomy. Methods: In accordance with PRISMA guidelines, all RCTs comparing TNK with BMT in adult patients between 4.5 and 24 h were systematically searched. The primary endpoint was good functional outcome at 90 days (mRS 0–2). Secondary endpoints included excellent outcome (mRS 0–1), symptomatic intracerebral hemorrhage (sICH), 90-day mortality, complete reperfusion at 24 h. Odd and Hazard ratios (ORs; HRs) were pooled using meta-analytic methods. Results: A total of seven RCTs involving 1754 patients were included. The rates of the primary endpoint were higher in TNK-treated patients (HR: 1.15; 95% CI: 1.03–1.27), as were rates of excellent functional outcome (HR: 1.29; 95% CI: 1.08–1.55). In the subgroup receiving intravenous therapy (IVT) alone, the primary endpoint was significantly more frequent in the TNK group than in the BMT group (OR: 1.47; 95% CI: 1.17–1.84; p for heterogeneity < 0.0001). TNK treatment was also associated with higher reperfusion rates compared with BMT, reflecting a greater proportion of saved ischemic penumbra as assessed via perfusion imaging. Although symptomatic intracranial hemorrhage (sICH) occurred more frequently in TNK-treated patients, the difference did not reach statistical significance, and mortality rates were comparable between treatment groups. Conclusions: Tenecteplase administered between 4.5 and 24 h is associated with improved rates of both good and excellent functional outcomes compared with BMT, especially in patients treated with IVT alone. Additionally, TNK is linked to higher rates of reperfusion.

Neurology International doi: 10.3390/neurolint18060115

Authors: Vera Marschal Andreas Ziebart Maryam Abdoullahi Daniel Werkmann Ralph König Thomas Kapapa Benjamin Mayer Johannes Rosskopf Lennart Marschal Christian Rainer Wirtz Andrej Pala Gregor Durner

Objective: To evaluate whether ABO blood group is associated with venous thromboembolic events (VTEs), cerebral severe vasospasm (CSV), delayed cerebral ischemia (DCI), and clinical or cognitive outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Materials and Methods: A retrospective observational two-center cohort study of collected registry data, including 169 patients treated between September 2021 and November 2025. Outcomes were compared across ABO subtypes using univariate testing and multivariable logistic regression. Results: No ABO subtype was independently associated with VTE (7.7%), CSV/DCI (21.9%), intracranial hemorrhage, or in-hospital mortality (all p > 0.05). Higher age (OR 1.08, 95% CI 1.031–1.144, p = 0.003) was independently associated with increased in-hospital mortality, whereas single peri-interventional antiplatelet therapy (PIAT) (OR 0.076, 95% CI 0.004–0.506, p = 0.029) was associated with lower in-hospital mortality. ABO blood group was not associated with functional outcome (mRS) or cognitive performance (MoCA) in this cohort. Conclusions: In this two-center retrospective cohort, no independent association between ABO blood group and early cerebrovascular complications, functional outcome, or cognitive outcome after aSAH was detected. These findings suggest that short-term prognosis may be more strongly influenced by established patient- and treatment-related factors, particularly age and single PIAT. Further studies with larger cohorts are warranted to clarify the potential effect of ABO blood group on outcomes after aSAH.

Neurology International doi: 10.3390/neurolint18060114

Authors: Kirti Sharma Baani Singh Sarabjit Mastana Monica Singh Puneetpal Singh

Ischemic stroke elicits a rapid and sustained innate immune response that critically contributes to blood–brain barrier (BBB) breakdown and secondary neuronal injury. Among the cellular mediators involved, neutrophil extracellular traps (NETs) have emerged as potent effectors of neurovascular damage. However, the regulatory mechanisms governing NET formation and their prolonged impact on BBB integrity remain incompletely understood. Increasing evidence indicates that NET formation is an epigenetically regulated process, requiring chromatin remodeling, histone modifications, DNA methylation changes and non-coding RNA-mediated control within neutrophils under ischemic conditions. These epigenetic events license the extrusion of DNA–histone–enzyme complexes that directly injure endothelial cells, degrade tight junction proteins, activate innate immune signaling pathways and amplify neuroinflammatory cascades at the neurovascular unit. Moreover, NET-derived chromatin and associated mediators can induce transcriptional and epigenetic alterations in BBB cells, thereby sustaining barrier permeability and impairing vascular repair mechanisms. In this review, we synthesize current knowledge on the epigenetic regulation of NET formation and delineate how epigenetically regulated NETs function as key disruptors of BBB integrity in ischemic stroke. Understanding this NETosis–epigenetics–BBB axis may uncover novel therapeutic strategies aimed at preserving neurovascular integrity and limiting post-stroke brain injury.

Neurology International doi: 10.3390/neurolint18060113

Authors: Danqing Xiao Akshita Duvvuri Lenna V. Makrigiannis Catherine Fuller

Alzheimer’s disease (AD), the leading cause of dementia, is characterized by progressive cognitive decline along with hallmark brain pathologies including amyloid-beta accumulation, hyperphosphorylated tau, neuroinflammation and neuronal mitochondrial dysfunction. As current pharmaceutical treatments only provide modest symptomatic improvement, there is an urgent need for effective non-pharmaceutical treatment options for the prevention or slowing down of this disease. This review synthesizes results from randomized controlled trials, observational studies, and animal model research on the ability of exercise to influence cognitive functions, brain structural changes, inflammatory processes, and neuroplasticity-related pathways. Exercise has demonstrated the capacity to enhance neurotrophic signaling, improve the regulation of mitochondria, improve cerebrovascular function and reduce pro-inflammatory cytokine levels in preclinical and mild cognitive impairment (MCI) subjects. Additionally, aerobic and resistance training has been shown to enhance physical performance and functional capacity. Furthermore, mind–body, dual-task and multimodal types of interventions may also provide additional cognitive and psychological benefits. Although the overall cognitive effect of exercise in individuals with established AD is generally small, it has been demonstrated that exercise can contribute to maintaining brain health through multiple interconnected metabolic, vascular and molecular pathways, thereby preserving cognitive reserve and slowing disease progression, particularly when initiated during early to midlife prior to the onset of AD symptoms. Therefore, future research will require establishing stage-specific exercise recommendations based on modality type, intensity and duration to achieve optimal clinical outcomes.

Neurology International doi: 10.3390/neurolint18060112

Authors: João Miguel Alves Ferreira Sergii Tukaiev Vaitsa Giannouli

RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid–liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.

Neurology International doi: 10.3390/neurolint18060111

Authors: Milan Aksic Ana Cirovic Orish Ebere Orisakwe Vuk Djulejic Bruna Puty Rafael Rodrigues Lima Aleksandar Cirovic

The pathophysiological basis of Parkinson’s disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson’s disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson’s disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency—known risk factors for Parkinson’s disease—lead to an increased cadmium burden and contribute to the onset and progression of the disease.

Neurology International doi: 10.3390/neurolint18060110

Authors: Geanina Cucu Ciuhan

Background/Objectives: Executive function (EF) impairments are common in neurodevelopmental disorders but are often examined using group-level approaches that may overlook clinically meaningful cognitive heterogeneity. This study explored EF heterogeneity in children with attention deficit hyperactivity disorder (ADHD), developmental dyslexia, and comorbid presentations using a clinically grounded mixed-method approach. Methods: Standardized neuropsychological data from the NEPSY-II, WISC-IV, and Woodcock–Johnson IV batteries were integrated with a case-based thematic synthesis of 11 clinical evaluations. Semi-inductive analysis was informed by preliminary patterns observed in a larger clinical sample. Results: Three executive function profiles were identified: (1) globally reduced executive functioning, characterized by widespread deficits in inhibition, attention, and working memory; (2) verbal–mnestic executive vulnerability, marked by weaknesses in verbal memory and attention regulation despite relative cognitive strengths; and (3) selective executive control deficit, reflecting impairments in inhibitory control and self-regulation. These profiles revealed clinically meaningful patterns that were not fully captured by categorical diagnostic classifications. Conclusions: The findings support the value of integrated, profile-based approaches for understanding executive function heterogeneity in neurodevelopmental conditions. Such approaches may enhance ecological validity in assessment and contribute to individualized intervention planning. Given the exploratory and case-based nature of the study, the findings should be considered preliminary and hypothesis-generating.

Neurology International doi: 10.3390/neurolint18060109

Authors: Giuseppe Marano Marianna Mazza

Background: Functional Neurological Disorder (FND) is a common and disabling condition at the interface of neurology and psychiatry, characterized by motor, sensory, seizure-like, or cognitive symptoms that are incongruent with recognized neurological disease but associated with substantial impairment. Despite its frequency and marked female predominance, FND remains underdiagnosed and often misunderstood. Methods: This narrative review synthesizes evidence from neurobiological, biomarker, and treatment studies, with attention to predictive coding, salience network dysfunction, impaired sense of agency, stress-related mechanisms, and sex- and gender-related vulnerability. Results: Current evidence supports a model of FND as a disorder of distributed brain network dysfunction involving abnormal interactions among salience, limbic, motor, and self-monitoring systems. Predictive coding and impaired agency models provide clinically useful frameworks for understanding symptom generation, although they remain mechanistic hypotheses rather than definitive causal explanations. Candidate biomarkers, including functional connectivity alterations, autonomic dysregulation, and HPA axis measures, offer pathophysiological insight but remain insufficiently validated for routine diagnosis. Female predominance likely reflects interacting biological, psychological, and sociocultural mechanisms rather than a single neuroendocrine pathway. Conclusions: This review contributes an integrated, clinically oriented framework linking neurobiology, biomarkers, sex/gender vulnerability, and treatment in FND. Current evidence supports multidisciplinary care combining diagnostic communication, specialized physiotherapy, psychotherapy, and coordinated follow-up, while future research should prioritize standardized phenotyping, longitudinal designs, and multimodal biomarker validation.

Neurology International doi: 10.3390/neurolint18060108

Authors: Shingo Miyata Shoko Shimizu Yugo Ishino

Oligodendrocytes (OLs) are specialized glial cells essential for the formation and maintenance of the myelin sheath within the central nervous system (CNS). Historically, OLs were considered a functionally homogeneous population. However, the advent and widespread application of single-cell and single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) technologies since 2015 have revealed substantial transcriptional heterogeneity, varying according to developmental stage, anatomical region, and disease state. In this review, we synthesized current advances in the understanding of OL heterogeneity. Nine OL cell classes have been identified in the mouse somatosensory cortex and hippocampal CA1 region, later expanding to 13 distinct subpopulations across ten CNS regions. Furthermore, we characterized disease-associated oligodendrocytes (DAOs)/disease-associated oligodendrocyte lineages (DOLs), identified in various neurological diseases, including multiple sclerosis (MS), Alzheimer’s disease (AD), and spinal cord injury, focusing on their molecular markers, spatial distribution, and pathophysiological roles. We summarized key transcriptional regulatory networks underlying DAO induction, including the signal transducer and activator of transcription (STAT)/interferon regulatory factor (IRF) family, the Yin Yang 1 (YY1)/nuclear factor kappa B (NF-κB) axis, and the SOX9/SOX10 regulatory system. The utility of region-specific brain analyses using spatial transcriptomics (ST) in conjunction with these approaches was also discussed. Finally, we compiled the implications of patient stratification according to white matter glial response patterns derived from large-scale snRNA-seq analyses of patients with progressive MS. Our synthesis shows that oligodendrocytes consist of multiple distinct subtypes that vary across development, brain regions, and disease conditions. In pathological states, they adopt specific disease-associated programs that reflect context-dependent responses and may influence disease progression and repair. This work provides a framework for understanding how oligodendrocyte diversity contributes to neurological disease and may support the development of targeted remyelination therapies.

Neurology International doi: 10.3390/neurolint18060107

Authors: Daniele Corbo Roberto Gasparotti Francesca Bozzetti Stefano Renzetti Laura Clara Grandi Antonio Vita Giacomo Deste

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a neurodevelopmental condition shaped by early-life biological and environmental factors. Emerging evidence highlights the role of nutrition in modulating key brain processes involved in ADHD, from gestational development through childhood. This review aims to examine how dietary interventions influence neuroimaging outcomes in individuals with ADHD, assessing whether nutritional approaches can modulate brain structure, function, or connectivity. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted to identify studies examining the effects of dietary interventions on neuroimaging outcomes in individuals with ADHD. Study quality was assessed using Cochrane RoB 2.0, ROBINS-I, the Newcastle–Ottawa Scale, and the JBI Critical Appraisal Checklist, according to study design. Results: A total of 1059 records were identified, and 4 studies met the final inclusion criteria. The included studies suggest that prenatal vitamin D exposure, omega-3 fatty acids, and micronutrients such as zinc may be associated with structural, functional, and neurometabolic brain characteristics relevant to ADHD. Reported findings included associations with brain volume, glutamatergic regulation, white matter organization, resting-state network integrity, and inattentive symptom. Conclusions: Current evidence supports the hypothesis that nutrition may influence neurodevelopmental processes involved in ADHD, including brain maturation and neural network organization. Although findings remain heterogeneous and limited in number, nutrition appears to represent a biologically plausible and potentially modifiable factor within the developmental framework of ADHD. Further longitudinal and multimodal neuroimaging studies are needed to clarify the mechanisms linking nutrition, brain development, and ADHD.

Neurology International doi: 10.3390/neurolint18060106

Authors: Thorsten Rudroff

In the original publication [...]

Neurology International doi: 10.3390/neurolint18060105

Authors: Tânia Silva Cesar Nunes Andreia Ribeiro Isabel Santana Joaquim Cerejeira

Background: White matter hyperintensities (WMHs) have been implicated in late-onset psychiatric disorders, but their contribution to this clinical phenotype remains insufficiently understood. Methods: We conducted a cross-sectional transdiagnostic study of 90 consecutively admitted acute patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) meeting the predefined inclusion criteria. Patients with a late onset were compared to earlier onset (EO) psychiatric patients. Late onset was defined as the median age of the disorder onset of the sample (≥40 years). Multidimensional clinical, cognitive, psychomotor, metabolic, and neuroimaging data were evaluated (WHM burden and cerebral atrophy), and a cognitive-psychopathologic composite index was derived. Correlations and sensitivity analysis were performed. A multivariable linear regression was performed to assess the independent effects of age, vascular risk factors, and WMH severity on cognitive performance and psychiatric symptoms. Results: In patients with LO psychiatric disorders, greater WMH burden was significantly associated with poorer global cognition and specific cognitive domains, lower delusional symptoms severity, and greater suicidal thoughts/behavior intensity. These associations were markedly weaker or not present in EO patients. The regression model explained 36.5% of the variance in the cognitive-psychopathologic composite index. After adjusting for age and cumulative risk factors, Fazekas was the only significant independent predictor (β = −0.495, p = 0.001). Conclusions: WMH burden was associated with differences in clinical characteristics in LO psychiatric disorders, including cognitive and neuropsychiatric symptoms. Our findings support a possible vascular-neuropsychiatric interaction in LO phenotypes.

Neurology International doi: 10.3390/neurolint18060104

Authors: Michal Fila Janusz Blasiak

Background/Objectives: Migraine may be associated with structural changes in the brain, including the cerebellum and brainstem. Some of these changes reflect the brain’s plasticity in adapting to migraine-related alterations, but others may influence the severity of migraines and resistance to treatment. Some studies report changes in cortical thickness among migraine patients, and focal cortical dysplasia (FCD) has been considered a possible cause of these changes. We argued that FCD could contribute to the development of migraine and the severity of its symptoms. To date, there has been no consistent report of FCD occurring in migraine patients. Case: A 29-year-old woman presented with a history of at least 19 years of high-frequency episodic migraine without aura. She experienced motion sickness during childhood and adolescence. Her condition worsened last year, evolving into chronic migraine, which was partially controlled by medications such as amitriptyline and rizatriptan, leading to high-frequency episodic migraines. An MRI conducted in 2024 showed a small area of signal abnormality in the left occipital lobe, believed to represent cortical dysplasia. A follow-up MRI after three months showed no changes in this area. She is currently diagnosed with high-frequency episodic migraine and demonstrated severe migraine-related disability, with a MIDAS score of 25, and a severe impact on daily functioning, with a HIT-6 score of 65. Conclusions: The case involves a worsening migraine that was somewhat alleviated by a pharmacological intervention. FCD may contribute to brain hyperexcitability in this case and her motion-related problems during childhood and adolescence. FCD could also play a role in the increasing severity of her migraines and her partial resistance to medication.

Neurology International doi: 10.3390/neurolint18060103

Authors: Leonardo Bradaschia Christian Heinen

Brachial plexus injuries are challenging conditions. Over the past decades, nerve transfer surgery has progressively evolved from proximal nerve reconstruction toward selective distal neurotization strategies, considerably expanding the possibilities for functional restoration. As the number of described donor–recipient combinations has increased, the literature has become increasingly fragmented, often focusing on isolated techniques or specific functional targets. The aim of the present study was to provide a comprehensive state-of-the-art overview of currently available motor nerve transfer strategies for upper-limb reinnervation in BPI. A literature review was conducted according to PRISMA guidelines using PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science databases. Studies concerning motor nerve transfers for upper-limb reconstruction were systematically reviewed and categorized according to recipient nerve and functional target, including shoulder function, scapular stabilization, elbow flexion and extension, wrist and finger extension, wrist and finger flexion, intrinsic hand function, and extraplexal donor nerve reconstruction. A total of 250 studies met the inclusion criteria. Both intraplexal and extraplexal donor strategies were identified for most reconstructive targets. Intraplexal distal nerve transfers currently represent the preferred approach whenever feasible because of shorter reinnervation distances and more predictable outcomes. Extraplexal donors, including the spinal accessory, intercostal, contralateral C7, and phrenic nerves, remain essential in complete BPIs and root avulsion injuries. Despite substantial advances, restoration of intrinsic hand function and reliable distal reinnervation remain major reconstructive challenges. Motor nerve transfers represent an increasingly versatile and function-oriented reconstructive strategy that should be tailored to the individual injury pattern, available donor nerves, and functional priorities.

Neurology International doi: 10.3390/neurolint18060102

Authors: Aya Ewida Dima Al-Qaimari Ubaid Shah Nikil Sudarsan

Introduction: Congenital myasthenic syndrome (CMS) is a rare hereditary disorder of the neuromuscular junction caused by pathogenic variants that affect acetylcholine transmission. We report three pediatric cases with CMS, including a rare homozygous CHRNE mutation previously described only once, a novel CHRNE compound heterozygous variant, and two novel DPAGT1 variants associated with limb-girdle CMS (LG-CMS), thereby expanding the known genetic and phenotypic spectrum of the disorder. Case presentation: The first patient, a 4-year-old girl born to consanguineous parents, presented with bilateral ptosis and fatigable weakness since infancy. Whole-genome sequencing revealed a homozygous CHRNE variant, c.991C>T. The second patient, a 4-year-old boy born to non-consanguineous parents, presented with congenital bilateral ptosis and ophthalmoplegia without generalized weakness. Genetic analysis identified compound heterozygous CHRNE variants, c.905C>G and c.1040T>C. Both patients demonstrated marked improvement with pyridostigmine therapy. The third patient, a 3-year-old girl born to non-consanguineous parents, presented with severe limb weakness requiring assistance in walking and performing daily activities with minimal ocular involvement, suggesting a diagnosis of LG-CMS. Genetic testing identified two novel variants in the DPAGT1 gene in the compound heterozygous form, c.710G>T and c.858C>A. The initial response to pyridostigmine diminished over time. Conclusions: These cases underscore the phenotypic heterogeneity of CMS, even within the same genetic subtype, and expand the existing mutational spectrum of CHRNE and DPAGT1 genes. This study also highlights the essential role of molecular diagnosis in distinguishing CMS from other neuromuscular disorders. Early genetic confirmation facilitates genotype-targeted therapy, prevents inappropriate immunosuppression, and enables informed reproductive counseling.

Neurology International doi: 10.3390/neurolint18060101

Authors: Viktoria Babacheva Kostadin Kostadinov Veselina Goranova-Marinova Miroslava Hristova Penka Atanassova

Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case–control study (2024–2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital “Sv. Georgi” Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (−2.26 unadjusted, p = 0.016; −2.83 doubly robust, p = 0.001), as were MMSE scores (−1.64, p = 0.015; −1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28–0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05–0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care.

Neurology International doi: 10.3390/neurolint18060100

Authors: Eray Halil Ivan Sitnikov Neli Atanasova Petra Popova Kostadin Kostadinov Fares Ezeldin Penka Atanassova

Background/Objectives: Artificial intelligence (AI) tools are increasingly integrated into acute stroke imaging workflows, but real-world performance for ischemia detection on non-contrast CT (NCCT) remains incompletely validated by investigators independent of the developer. This study externally validated the BrainScan AI system in an unselected, consecutively enrolled emergency cohort. Methods: Consecutive adult patients undergoing NCCT under the routine acute stroke protocol at a single tertiary centre between January and December 2025 were prospectively enrolled. The reference standard was the post-consensus radiological diagnosis, supplemented where available by follow-up imaging and clinical course. Primary outcomes were diagnostic accuracy for ischemia and intracranial haemorrhage detection, assessed by sensitivity, specificity, predictive values, likelihood ratios, and area under the ROC curve (AUC; DeLong). Pre-specified secondary analyses included regional sensitivity, confidence-score behaviour, artefact robustness, threshold sensitivity, a cluster-robust bootstrap for within-patient correlation, and a quantitative bias analysis under non-differential reference-standard misclassification. Sample size adequacy was assessed using a precision-based framework. Results: A total of 1419 NCCT examinations from 1260 patients were analysed. Ischemia sensitivity was 59.2% (95% CI 52.1–66.1) and specificity was 99.8% (99.4–100), with an AUC of 0.930 (0.906–0.954). The Youden-optimal threshold (0.055) recovered sensitivity to 86.1% with negligible specificity loss, reflecting a markedly bimodal score distribution. Regional sensitivity was lower in infratentorial structures. Bias-corrected estimates were stable across all reference-standard parameters consistent with the data. Haemorrhage detection performed substantially better (sensitivity 96.7%; AUC 0.983). Conclusions: The system shows excellent specificity and strong discrimination but moderate sensitivity for ischemia, supporting its role as a rule-in adjunct rather than a stand-alone tool, pending multicentre validation and site-specific threshold recalibration.

Neurology International doi: 10.3390/neurolint18050099

Authors: Shachar Zion Shemesh Paz Kelmer Jose Asprilla Yotam Hadari Omri Cohen Lior Ungar

Background: Trigeminal neuralgia (TN) is clinically defined, but patients presenting to tertiary practice with trigeminal-region pain are often diagnostically heterogeneous and may follow prolonged medication, dental, imaging, and procedural pathways before a stable phenotype is established. We aimed to characterize diagnostic phenotypes, secondary causes, and treatment-escalation patterns in a large retrospective tertiary-center trigeminal pain cohort derived from routine free-text clinical documentation. Methods: We conducted a retrospective single-center cohort study based on a clinical dataset containing 18,007 note fragments linked to 672 unique patient records between 12 October 2010 and 21 April 2026. A rule-based natural-language-processing-assisted chart review framework was used to identify patients with trigeminal pain and to extract documentation-derived demographic features, pain distribution, secondary causes, dental pathway variables, imaging signals, medication exposure, procedures, and outcome language. Patients were grouped into primary/classical TN, secondary TN/trigeminal pain, and dental-first or mimic pathways using predefined operational criteria. Results: A total of 455 patients met criteria for the analytic trigeminal pain cohort; 311 (68.4%) carried explicit TN terminology. Mean age was 58.7 years, median age 60 years, and 267 of 428 patients with recoverable sex data (62.4%) were women. Trigeminal branch involvement could be extracted in 351 patients (77.1%), with V2 involvement documented in 256 (56.3%), V3 involvement in 218 (47.9%), and V1 involvement in 138 (30.3%). The final NLP-derived phenotypic distribution comprised 201 primary/classical TN cases (44.2%), 146 secondary TN/trigeminal pain cases (32.1%), and 108 dental-first or mimic presentations (23.7%). MRI was documented in 384 patients (84.4%), neurovascular conflict or vascular loop in 253 (55.6%), multiple-sclerosis-related disease in 69 (15.2%), and tumor-related trigeminal involvement in 84 (18.5%). Prior dental evaluation was identified in 169 patients (37.1%), and prior dental procedures in 114 (25.1%). Carbamazepine exposure was documented in 367 patients (80.7%), pregabalin in 221 (48.6%), gabapentin in 150 (33.0%), oxcarbazepine in 116 (25.5%), and phenytoin in 73 (16.0%). At least one invasive or image-guided procedure was documented in 390 patients (85.7%), including nerve blocks/injections in 355 (78.0%), radiofrequency procedures in 126 (27.7%), balloon compression in 90 (19.8%), microvascular decompression in 113 (24.8%), and stereotactic radiosurgery in 55 (12.1%). Dental-first patients were significantly more likely to have undergone prior dental procedures (65.7% vs. 3.5% in primary/classical TN and 24.7% in secondary TN; p < 0.001), whereas secondary TN/trigeminal pain was associated with higher use of radiofrequency procedures (36.3%; p = 0.017), higher use of stereotactic radiosurgery (19.9%; p = 0.002), higher recurrence documentation (70.5%; p = 0.001), and a higher rate of complete pain relief documented at last follow-up (46.6%; p = 0.004). Conclusions: In tertiary practice, trigeminal pain is substantially broader than a formal TN label. Secondary disease and dental-first pathways account for a large fraction of referrals, and management is characterized by heavy medication burden, frequent escalation, and recurrent retreatment. A structured phenotyping approach may help convert routine clinical documentation into a clinically meaningful framework for diagnostic triage and treatment selection, although imaging and outcome variables require cautious interpretation when derived from retrospective free text.

Neurology International doi: 10.3390/neurolint18050098

Authors: Pranjal Rai Daniel Mandel Girish Bathla Vidhi Dhaduk Radhika Rajeev Jay Kakadiya Huanwen Alvin Chen Hamza A. Salim Ahmed Y. Azzam Muhammed Amir Essibayi Brian Connolly Marc Buzzelli Vivek S. Yedavalli Majid Khan Adam A. Dmytriw David J. Altschul Matthew K. McIntyre Marco Colasurdo Ajay Malhotra Dheeraj Gandhi Dhairya A. Lakhani

Background: Asymptomatic intracranial atherosclerotic arterial stenosis (ICAS) is an underrecognized entity for which vascular risk-factor optimization is the primary management strategy, with no current indication for routine antiplatelet therapy or endovascular intervention for primary stroke prevention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, including stroke, in high-risk cardiometabolic populations, but their association with outcomes in asymptomatic ICAS is yet to be evaluated. The present study aims to evaluate the association between GLP-1RA use and cerebrovascular outcomes in adults with asymptomatic ICAS. Materials and Methods: We used the TriNetX US Collaborative Network (71 healthcare organizations) to identify adults (≥18 years) with ICAS between 1 January 2016 and 31 December 2025, and excluded patients with prior cerebral infarction, intracranial hemorrhage, or cerebrovascular ischemic syndromes. Exposure was defined as initiation of any GLP-1 receptor agonist (lixisenatide, semaglutide, liraglutide, tirzepatide, dulaglutide) during the 6 months before or on the date of index ICAS diagnosis. Outcomes were assessed at 1 year, and included ischemic stroke, all-cause mortality, and a composite of ischemic stroke or mortality. Propensity-score matching (1:1) was performed, including demographics, vascular risk factors, comorbidities, antithrombotics, lipid/diabetes therapies, and cardiometabolic laboratory/physiologic measures. Results: Before matching, 1746 GLP-1RA users and 71,792 non-users met inclusion criteria; after matching, 1728 patients remained in each cohort. GLP-1RA use was associated with lower 1-year risk of ischemic stroke (4.40% vs. 6.10%; hazard ratio [HR] 0.70, 95% CI 0.52–0.95; p = 0.044), lower all-cause mortality (3.40% vs. 9.40%; HR 0.35, 95% CI 0.26–0.47; p < 0.001), and lower composite outcome risk (7.50% vs. 15.00%; HR 0.48, 95% CI 0.39–0.59; p < 0.001). Notably, these associations were observed despite matching for HbA1c, LDL cholesterol, BMI, and systolic blood pressure, suggesting potential effects beyond measured cardiometabolic risk profiles. Conclusions: In this large, propensity-matched cohort of adults with a-ICAS, GLP-1RA use was associated with lower ischemic stroke, all-cause mortality, and composite outcome at 1 year. These findings are hypothesis-generating and require further prospective studies to confirm this observation.

Neurology International doi: 10.3390/neurolint18050097

Authors: Tatiana M. Medvedeva Maria P. Smirnova Lyudmila V. Vinogradova

Background/Objectives: Cortical spreading depolarization (SD) is recognized as the pathophysiological substrate of migraine aura. Suppression of ongoing cortical activity produced by SD is thought to underlie the transient neurological deficits characteristic of the aura phase. While cortical hyperexcitability is a well-established feature of migraine brain, the effect of SD on spontaneous electrical activity in the hyperexcitable cortex remains poorly understood. Here, we investigate how SD and SD-induced depression of cortical activity are modulated by a state of mildly enhanced excitability. Methods: Using freely behaving rats, we assessed characteristics of SDs, electrocorticographic spectral power in the frontal and occipital cortices during interictal period and after SD initiation, under both drug-free conditions and following mild pharmacological disinhibition. Results: Mild cortical disinhibition resulted in a significant increase in baseline oscillatory power relative to control conditions. While cortical hyperexcitability did not alter the properties of SD itself, it differentially modulated the impact of SD on spontaneous activity in a region-specific manner. Notably, under conditions of enhanced excitability, the duration of SD-induced depression was markedly reduced in the frontal cortex but prolonged in the occipital cortex. Conclusions: These findings demonstrate that the effects of SD on spontaneous cortical activity are critically dependent on the baseline level of cortical excitability and exhibit distinct regional heterogeneity. In the awake, hyperexcitable state, the occipital cortex shows heightened vulnerability to SD-induced depression, a finding that may provide a mechanistic basis for the disproportionate involvement of the occipital cortex in aura generation and the predominance of visual symptoms in migraine aura.

Neurology International doi: 10.3390/neurolint18050096

Authors: Dinesh Devadoss Juliet Akkaoui Arti Vashist Adriana Yndart Arias Adel Nefzi Madepalli K. Lakshmana

Background/Objectives: Yes-associated protein 1 (YAP1) is a transcriptional cofactor that coordinates the complex interplay between cell proliferation, survival, differentiation, metabolism, biomechanics, and tissue regeneration. Previous studies have shown that YAP1 activity is reduced during aging, and replacing YAP1 function has been shown to rejuvenate old cells by mitigating senescence and its associated inflammation. Methods: As YAP1 is now confirmed to exert a profound regenerative influence on multiple organs, we wanted to gain more insight into the molecular signature of YAP1 expression relevant to brain cells. Since proteomics is a very powerful tool for discoveries, we generated SH-SY5Y cells stably expressing GFP-YAP1 and screened 8000 human proteins using multiplex arrays that utilize biotin-label-based antibody arrays. Results: We found YAP1 expression in astrocytes, microglia, neuronal and neuroblastoma cell lines, as well as human neurons. Importantly, YAP1 protein levels were significantly reduced selectively in the nuclear fractions of the brains of patients with Alzheimer’s disease (AD) relative to normal control (NC) subjects. The screen resulted in the identification of 283 differentially expressed proteins. In line with YAP1’s known role in the regulation of actin and cytoskeleton, we found a 2.53-fold upregulated level of Rho guanine nucleotide exchange factor 1 (ARHGEF1), a guanine nucleotide exchange factor (GEF) for the RhoA GTPase, which is crucial for dendritic spine regulation. A 6.19-fold upregulated level of NECAP endocytosis-associated 2 (NECAP2), the highest known increase for any protein in this screen, plays an essential role in clathrin-mediated endocytosis. Most importantly, another upregulated protein was Neudesin Neurotrophic Factor (NENF) (3.07-fold increase), also known as Neudesin, which primarily acts as a neurotrophic factor, and it promotes neuronal survival, enhances cell proliferation, and neurogenesis in neural progenitor cells. Neural Precursor Cell Expressed, Developmentally Down-Regulated 9(NEDD9) levels were also upregulated by 2.46-fold, and it affects neuronal cell number and synaptic connections through its role in neurite formation. However, it should be noted that these proteomic results are preliminary in nature as they are derived from single-sample data. The upregulated levels of ARHGEF1 and NEDD9 were confirmed by immunoblots. We also found a drastic reduction in the levels of p16INK4a, a marker of senescence. Conclusions: Thus, the anti-senescence effect of YAP1 may be mediated through p16INK4a, which in turn may be crucial for YAP1’s regenerative functions through NENF and NEDD9.

Neurology International doi: 10.3390/neurolint18050095

Authors: Marija Nikola Jansone Nauris Zdanovskis Elina Polunosika Daina Pastare Guntis Karelis

Background/Objectives: Multiple sclerosis (MS) remains challenging to diagnose due to clinical and radiological overlap with mimicking conditions. The 2024 revisions of the McDonald criteria have incorporated the central vein sign (CVS) and paramagnetic rim lesions (PRLs) as magnetic resonance imaging (MRI) biomarkers to improve diagnostic specificity. This study assessed the prevalence and anatomical distribution of CVS and PRLs in patients with relapsing–remitting MS (RRMS). Methods: This cross-sectional study included 91 patients with RRMS diagnosed according to the 2017 McDonald criteria. MRI scans were obtained using 3T scanners, and T2-FLAIR and susceptibility-weighted angiography (SWAN) sequences were analyzed. CVS and PRLs were identified using established criteria. Patients were stratified by lesion count (<5, 5–9, ≥10), and lesions were categorized by anatomical location. Descriptive statistics, chi-square tests, and multivariable logistic regression adjusted for covariates were performed. Results: CVS was present in 69.2% of patients, while PRLs were identified in 29.7%. Both markers were more frequent in patients with higher lesion burden in univariate analysis. CVS prevalence increased significantly with lesion count (p < 0.001) and remained an independent predictor in multivariable logistic regression. PRL presence was associated with lesion count in univariate analysis but not after adjustment. Most CVS- and PRL-positive lesions were supratentorial and predominantly periventricular. No significant association was observed between CVS and PRL presence. Conclusions: CVS is a highly prevalent MRI feature in RRMS and independently associated with lesion burden, supporting its role as a diagnostically relevant imaging marker. PRLs were less prevalent and showed weaker independent associations.

Neurology International doi: 10.3390/neurolint18050094

Authors: Prasad Vannemreddy Konstantin V. Slavin

Background/Objectives: Vagus nerve stimulation (VNS) has evolved from a laboratory experiment to a standard of care in several neurological disorders like epilepsy, depression and stroke rehabilitation at present. Methods: We reviewed the published literature relevant to its origins in animal models leading to various clinical applications. Results: Bailey and Bremer published their observations following VNS in animals while further studies established its utility in some forms of epilepsy. Subsequent observations in epilepsy patients treated with VNS revealed the unequivocal improvement in psychological and behavioral disorders. Consequently, VNS received approval for its application in resistant depression disorders. Multiple studies revealed changes due to neuronal plasticity following VNS that could result in the significant clinical recovery of motor function in chronic ischemic stroke patients. Chronic incomplete cervical spinal cord injury, head injury and peripheral nerve injury deficits are also being studied for recovery patterns. Transcutaneous approaches and closed-loop stimulation are showing encouraging results that may facilitate the extension of the application of neuromodulation using VNS. Conclusions: For the recovery of motor function following paralysis in stroke patients or cervical spinal cord injuries, the timing of the stimulation after physical activity during rehabilitation has been identified as a key factor. In addition to the timing of the stimulation, the titration of the parameters is also being studied to obtain optimized recovery in cases of motor, sensory, or sphincter deficits.

Neurology International doi: 10.3390/neurolint18050092

Authors: Vlad-Petru Morozan Mihai Stancu Mara Ioana Ionescu Ana-Maria Catrina Alexandra Mocanu Vladimir Suhăianu Andrei-Vladimir Iacovache Ana-Teodora Chirilă Andrei Bordeianu Leon Zăgrean Ana-Maria Zăgrean Mihai Moldovan

Background/Objectives: Birth asphyxia is a frequent neonatal complication in humans. Its outcome is variable, and the factors underlying this variability remain incompletely understood. Maternal gut microbiome impairment has been proposed as one factor that may influence offspring neurodevelopment, especially when the immature brain is exposed to additional vulnerability such as perinatal asphyxia (PA). Building on our previous maternal microbiome disruption model and on our prior observation that electroencephalography (EEG) reactivity to photic stimulation under deep anesthesia detects functional impairment two months after PA, we assessed whether this reactivity was further impaired after prolonged gestational antibiotic administration and whether probiotics modulated this effect. Methods: Wistar dams received antibiotics, probiotics, antibiotics with probiotics, or control treatment, and offspring underwent PA. Adult EEG reactivity to photic stimulation was assessed during chloral hydrate-induced burst suppression. Burst count reactivity (BCR) was used as the primary event-based readout of stimulus-evoked burst recruitment and was compared with the suppression-ratio-based burst-suppression reactivity index (BSRi). Results: Burst suppression remained reactive to photic stimulation in all groups. BCR was lower after gestational antibiotic treatment than in controls. The magnitude of the effect was attenuated by probiotics coadministration. BSRi showed the same overall pattern. Conclusions: Prolonged gestational antibiotic exposure increased the severity of perinatal asphyxia as measured by EEG reactivity in the adult offspring. The converging BCR and BSRi results support burst-suppression reactivity as a functional neurophysiological readout in this PA model and support further methodological development of EEG reactivity measures for translational studies of hypoxic–ischemic brain injury.

Neurology International doi: 10.3390/neurolint18050093

Authors: Atsushi Nakayashiki Kunihiko Umezawa Yasuo Nishijima Ryutaro Suzuki Michiko Yokosawa Hidenori Endo

Background/Objectives: The optimal upfront modality selection for real-world aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We evaluated outcomes after an institutional change from an endovascular treatment (EVT)-first default to a modality-neutral individualized pathway. Methods: This single-center retrospective before-and-after cohort study included consecutive patients with aSAH who underwent aneurysm securing during two fixed time periods (pre-change: 1 May 2023 to 31 July 2024; post-change: 1 August 2024 to 31 October 2025). The primary outcome was a favorable 90-day modified Rankin Scale (mRS) score of 0–2. The primary analysis used Firth penalized logistic regression adjusted for age, pre-morbid mRS ≥ 2, and World Federation of Neurosurgical Societies grade IV–V. Conventional logistic regression and ordinal mRS shift analysis were performed as sensitivity analyses. Results: A total of 104 patients were included (pre-change, n = 48; post-change, n = 56). EVT decreased from 79.2% to 37.5%, and microsurgery increased from 20.8% to 62.5% (p < 0.001). Favorable outcomes occurred in 25/48 patients (52.1%) in the pre-change period and 36/56 patients (64.3%) in the post-change period (p = 0.235). In adjusted analyses, the post-change period was associated with favorable outcome (aOR 3.82; 95% CI, 1.31–12.79; p = 0.009), consistent with the sensitivity analysis (aOR, 4.41; 95% CI, 1.43–15.95; p = 0.009). Shift analysis also favored the post-change period (adjusted common OR, 2.36; 95% CI, 1.15–4.91; p = 0.021). Secondary outcomes and procedure-related complications were similar between the two periods. Conclusions: A shift from an EVT-first default to a modality-neutral individualized pathway was associated with more favorable adjusted 90-day functional outcomes. Multicenter confirmation is warranted.

Neurology International doi: 10.3390/neurolint18050091

Authors: Sagrario Pérez-de la Cruz

Background/Objectives: Stroke remains a leading cause of global disability, with upper limb impairment affecting over 80% of patients. During the acute phase (first seven days), a critical neuroplastic window exists where interventions may significantly influence recovery. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of electrical stimulation—specifically Functional Electrical Stimulation (FES) and Neuromuscular Electrical Stimulation (NMES)—on upper limb functional recovery and complication prevention during the acute phase of stroke. Methods: A systematic search was conducted across eight databases (including Medline, PEDRo, and Cochrane) for randomized and non-randomized clinical trials published between 2016 and 2025. Methodological quality was assessed using the PEDRo scale. Quantitative synthesis was performed via meta-analysis using a random-effects model, focusing on the Fugl-Meyer Assessment (FMA-UE). Results: Eight randomized clinical trials were selected with a total of 384 participants. The meta-analysis results showed a positive and statistically significant effect in favor of the experimental group compared to the control group (Z = 2.39; p = 0.02), with a combined Standardized Mean Difference of 0.53 (95% CI: 0.10 to 0.96), indicating a moderate effect size on the Fugl-Meyer Assessment Upper Extremity scale. Although high heterogeneity was detected (I2 = 74%), the analysis suggests that Functional Electrical Stimulation (FES) and Neuromuscular Electrical Stimulation (NMES) improve manual dexterity, prevent disuse atrophy, and reduce glenohumeral subluxation. Conclusions: Electrical stimulation shows a positive trend in early stroke recovery; however, it should be considered a promising adjunct rather than a definitive treatment. Further research into standardized protocols is required to confirm their clinical significance.

Neurology International doi: 10.3390/neurolint18050090

Authors: Andreas K. Demetriades

Surgical mastery has transformed treatment, but diagnosis, neuroprotection, and recovery remain the field’s next frontier [...]

Neurology International doi: 10.3390/neurolint18050089

Authors: Alfonso Martinisi Paolo Paganetti

To this day, the etiology of multiple sclerosis has yet to be fully comprehended by the scientific community. However, the knowledge on mechanisms leading to the development of this neurodegenerative autoimmune disorder increases daily, along with the development of new disease-modifying treatments. A correlation between Epstein–Barr Virus infection and the disease incidence has recently shed light on possible innovative antiviral therapies. Here, we review the literature on Human Endogenous Retroviral sequences as emerging actors for the impairment of remyelination as a major challenge in disease progression. Our primary focus is the HERV-W envelope protein, which has been found at elevated levels in individuals affected by this condition and is suggested here as a potential therapeutic target. We then continue analyzing the clinical cases where antiretroviral drugs have been tested to treat multiple sclerosis patients and, from successes and failures, we finally narrow down our therapeutic hypothesis to the administration of Nucleoside-analog Reverse Transcriptase Inhibitors to target the HERV-W envelope protein, possibly leading to remyelination and significantly improving the condition of those affected by the disease. The main purpose of this review is to present a rationale for the therapeutic potential of this drug class and offer a new perspective for therapeutic options against multiple sclerosis.

Neurology International doi: 10.3390/neurolint18050088

Authors: Mohammad Amran Hossain Enea Traini Francesco Amenta

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects millions globally, particularly those in the elderly population. Several occupational exposures typical of maritime environments are recognized or suspected risk factors for PD, warranting attention within occupational health frameworks. The disease is characterized by motor symptoms such as tremor, rigidity, and bradykinesia, as well as non-motor impairments including speech abnormalities. Objective: Early diagnosis is crucial for effective disease management but remains challenging due to symptoms overlapping with normal aging and other neurological conditions. This study presents a machine learning (ML)-based approach for the early diagnosis of PD using speech signal analysis. Methods: We employed six supervised ML classifiers to differentiate between PD patients and healthy controls based on vocal features. The experimental dataset, MDVR-KCL, consists of speech recordings from both reading tasks and spontaneous dialogs, collected via mobile devices. From these recordings, we extracted Mel-Frequency Cepstral Coefficients (MFCCs), Gammatone Frequency Cepstral Coefficients (GTCCs), and acoustic features such as jitter, shimmer, and harmonic-to-noise ratio. These features capture a broad range of prosodic, spectral, and articulatory characteristics associated with PD-related speech impairments. Speaker diarization was applied in spontaneous dialog recordings to separate participant speech. Hyperparameter tuning was performed using GridSearchCV with 10-fold cross-validation, while final model evaluation was conducted using Leave-One-Subject-Out Cross-Validation (LOSOCV) to ensure subject-independent performance assessment. Results: In the read-text task, the SVM model performed exceptionally, yielding 95.45% accuracy, 94.62% sensitivity, 95.97% specificity, an F1-score of 94.12%, and an AUC of 0.98 with an MCC value of 0.90, for GTCCs with the acoustic features. In the spontaneous dialog task, the XGB model demonstrated the highest overall performance across all metrics, with a test accuracy of 83.7%, a sensitivity of 76.3.9%, a specificity of 88.9%, an F1-score of 79.5%, an AUC value of 0.88, and an MCC value of 0.66. Conclusions: Comparable results were obtained on both spontaneous dialog and reading speech subsets, demonstrating the robustness of the approach across different speaking contexts. These results demonstrate the effectiveness of integrating cepstral and acoustic features with machine learning models for non-invasive PD classification. The findings support the use of speech-based digital biomarkers in early PD detection and highlight the potential for developing scalable tools. This work highlights the potential of speech-based digital diagnostics to support clinical decision-making and improve patient outcomes.

Neurology International doi: 10.3390/neurolint18050087

Authors: Almir Fajkić Andrej Belančić Kristina Pilipović Valentino Rački Silvestar Mežnarić Tamara Janković Elvira Meni Maria Gkrinia Dinko Vitezić Jasenka Mršić-Pelčić

Spinal muscular atrophy (SMA) therapies that restore SMN expression improve survival and motor function but often fail to fully stabilize distal motor units or sustain endurance. We propose a hypothesis-driven adjunctive approach, intended to complement SMN-restoring therapies, in which localized nanotube-enabled interfaces acting at or near the distal motor unit and neuromuscular junction enhance neuromuscular transmission reliability in surviving, remodeled motor units. The model predicts a temporal cascade: improved junctional reliability and reduced activity-dependent failure, followed by consistent motor unit output across repeated activation, and ultimately, enhanced endurance and functional reserve. Phenotype-specific responsiveness identifies patients most likely to benefit, specifically those with preserved-but-limited residual motor unit substrate accompanied by measurable neuromuscular junction instability. Drawing on shared mechanisms from ALS, spinal cord injury, and other neuromuscular disorders, we discuss mechanistic, translational, safety, regulatory, and ethical considerations. This framework links objective physiological constructs to functional outcomes, offering a mechanistically grounded path for adjunctive therapy development in SMA and related conditions.

Neurology International doi: 10.3390/neurolint18050086

Authors: Georgi V. Vasilev Sonya Ivanova Ivan Milanov

The conventional classification of multiple sclerosis (MS) into relapsing–remitting, secondary progressive, and primary progressive phenotypes has long guided diagnosis, prognosis, and therapeutic decision-making. However, accumulating evidence indicates that disability accumulation frequently occurs independently of clinical relapses, challenging relapse-centric and phenotype-based models of disease evolution. The concept of progression independent of relapse activity (PIRA) has emerged as a clinically relevant framework capturing this phenomenon across MS phenotypes. In this state-of-the-art narrative review, we propose a spectrum-based reinterpretation of MS, integrating PIRA with concepts of smouldering-associated worsening and neurologic reserve. We highlight the heterogeneity of relapse-independent worsening, distinguishing transient from persistent PIRA, and discuss how ageing-related decline in compensatory capacity contributes to the clinical unmasking of progression over time. Within this framework, secondary progressive MS is redefined as the clinically recognizable accumulation of persistent relapse-independent worsening, while primary progressive MS is conceptualized as early predominance of clinically manifest progression due to limited reserve rather than a distinct disease entity. Finally, we examine diagnostic and therapeutic implications of a spectrum-based model in the contemporary era, emphasizing the limitations of relapse-centric treatment strategies and unmet needs in addressing progression-related biology. By reframing MS as a dynamic continuum shaped by the interaction between ongoing pathology and evolving neurologic reserve, this review aims to support earlier recognition of clinically meaningful progression and to inform more biology-aware approaches to disease monitoring and therapy.

Neurology International doi: 10.3390/neurolint18050085

Authors: Saeed Mahmood Mohammad Asim Ayman El-Menyar Sandro Rizoli Hassan Al-Thani

Traumatic spinal cord injury (TSCI) frequently necessitates prolonged ventilatory support, raising the clinical dilemma of early versus late tracheostomy. Despite decades of debate, no randomized controlled trials (RCTs) have been conducted exclusively in TSCI populations, and evidence remains largely observational. This review synthesizes contemporary evidence on the timing and outcomes of tracheostomy in acute TSCI. Across multiple cohort studies and meta-analyses, early tracheostomy (≤7 days) is consistently associated with shorter mechanical ventilation duration, shorter ICU length of stay, reduced sedation exposure, and fewer immobility-related complications. Data suggested a lower incidence of ventilator-associated pneumonia, though mortality outcomes remain unchanged. Importantly, cervical-level injuries appear to derive the most significant benefit, while variability in defining “early” versus “late” complicates direct comparisons. Despite methodological limitations, including reliance on retrospective data, inconsistent definitions, and lack of long-term follow-up, cumulative evidence indicates that early tracheostomy improves short-term outcomes. The optimal timing of tracheostomy in TSCI remains uncertain. Current observational evidence suggests that early tracheostomy in cervical SCI is associated with a reduction in the duration of mechanical ventilation, ICU stay, and respiratory complications. These benefits might come from better access to the airways, less anatomical dead space, better clearance of secretions, less need for sedation, together with earlier mobilization and rehabilitation. Mortality outcomes remain inconclusive. In the absence of randomized trials and long-term data, individualized decisions based on injury level, clinical course, and institutional expertise are essential.

Neurology International doi: 10.3390/neurolint18050084

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

Background: Vascular dysfunction and neurovascular inflammation are increasingly recognized as contributors to Alzheimer’s disease (AD) pathophysiology, particularly through interactions with tau-related neurodegeneration. Endothelial adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), play key roles in blood–brain barrier regulation and immune-vascular crosstalk, yet their relevance to long-term disease progression and established AD biomarkers remains incompletely understood. Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we examined associations between baseline cerebrospinal fluid (CSF) levels of VCAM-1 and ICAM-1 and clinical progression, CSF biomarkers, neuroimaging measures, and cognitive outcomes over up to 10 years of follow-up. This study included 294 participants (87 cognitively normal, 129 with mild cognitive impairment, and 78 with AD). Multivariable logistic regression was used to assess associations with diagnostic progression, and linear regression models examined relationships with baseline and longitudinal measures of tau, amyloid-β, hippocampal volume, Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) metabolism, and cognition. Models were adjusted for age, sex, apolipoprotein E epsilon 4 (APOE ε4) status, baseline diagnosis, and baseline CSF amyloid-β, with false discovery rate correction applied for multiple comparisons. Results: Baseline CSF VCAM-1 and ICAM-1 levels did not differ across diagnostic groups. However, higher baseline levels of both markers were nominally associated with increased odds of disease progression. Notably, ICAM-1 showed a strong and robust association with baseline CSF phosphorylated tau, which remained significant after multiple-comparison correction. VCAM-1 was also associated with tau pathology, though this did not survive correction. Neither marker was associated with baseline or longitudinal changes in hippocampal volume, FDG-PET metabolism, or cognitive performance. Conclusion: CSF VCAM-1 and ICAM-1 appear to reflect neurovascular inflammatory processes linked to tau pathology rather than markers of clinical stage or longitudinal neurodegeneration. These findings support a role for endothelial activation in AD pathophysiology and highlight vascular–immune mechanisms as potential contributors to tau-related disease vulnerability.

Neurology International doi: 10.3390/neurolint18050083

Authors: Liwen Zhou Cathy Z. Yang George D. Bittner

Background/Objectives: Self-mutilation behavior is often triggered by neuropathic pain associated with peripheral nerve injuries (PNIs). Polyethylene glycol (PEG)-fusion is a repair method that rapidly joins/fuses the open ends of closely apposed severed axons, greatly reduces Wallerian degeneration, and restores sensorimotor behavior much more rapidly than current clinical procedures. Here, we examined whether the improved sensorimotor behavior recovery following PEG-fusion repair of sciatic nerve injuries compared to Negative Controls (NC) correlated with self-mutilation. We also examined six variables (repair method, behavioral tests, sex, injury type, strain, and surgical experience) that could influence self-mutilation outcomes. Methods: The Sciatic Functional Index (SFI) and the Von Frey (VF) behavioral tests were performed and analyzed. Regression and other analyses were performed to determine the independent effect of six variables on self-mutilation rates and severity. Results: PEG-fused rats that had no self-mutilation had significantly better SFI scores than those that had self-mutilation. More rapid VF sensory recovery in PEG-fused rats was also associated with less self-mutilation. Self-mutilation rates and severity were: (1) significantly reduced following PEG-fusion repairs compared to NCs; (2) significantly increased following weekly VF tests; (3) not different between female and male rats or (4) between simple transection and segmental-loss PNIs; (5) non-existent in Lewis rats and significantly less severe in Sprague Dawley rats than Long Evans rats; and (6) significantly reduced in rats operated on by experienced PEG-fusion surgeons who historically achieved better SFI outcomes than trainee surgeons. Conclusions: Our data suggest potential clinical benefits of PEG-fusion repair to produce more rapid and better sensorimotor recoveries and reductions of self-mutilation behaviors.

Neurology International doi: 10.3390/neurolint18050082

Authors: Brigitta Ruszin-Perecz Réka Héjas Alexandra Makai Nándor Hajdu Dalma Jedlicska Bence Ruszin-Perecz Andrea Sipos Endre Pál Dávid Varga

Background/Objectives: The Individualized Neuromuscular Quality-of-Life Questionnaire (INQoL) is a widely used measure of quality of life in patients with various neuromuscular diseases. This study aimed to adapt and test the validity and reliability of this measure in Hungarian patients with neuromuscular disease. Methods: According to the widely accepted method of validation, we first translated the original INQoL version into Hungarian, and then a native English speaker translated it back into English to test its validity. Following a pretest procedure, the INQoL was administered to 80 patients with various muscular diseases and 30 age-matched controls. The internal consistency and test–retest reliability were assessed. Concurrent validity was measured using the 36-item Short Form Survey (SF-36) questionnaire. Results: For all INQoL subscales, Cronbach’s alpha was above 0.7, demonstrating the reliability of the subscales. The highest Cronbach alpha value was for the Weakness subscale (0.983) and the lowest for the Treatment subscale (0.794). The intraclass correlation coefficient test values ranged from 0.810 (Treatment) to 0.988 (Pain), indicating excellent test–retest reliability. There was a strong correlation between the SF-36 Physical Function and multiple INQoL subscales, including Weakness (r = 0.754, p < 0.001), Fatigue (r = 0.704, p < 0.001), Activities (r = 0.744) p < 0.001, Independence (r = 0.791 p < 0.001), Body Image (r = 0.714 p < 0.001), and overall Quality of Life (r = 0.742 p < 0.001). Conclusions: Our findings indicate that the Hungarian-language adaptation of the questionnaire possesses adequate reliability and construct validity for assessing the quality of life in patients with muscular disorders.

Neurology International doi: 10.3390/neurolint18050080

Authors: Robert Constantin Zgarbura Leea Cristescu Rizea Madalin Dinca Alexandru Pavel Oana-Andreea Parliteanu Jari Sabri Catalina Tudose

Background: Migraine is a highly prevalent neurological disorder associated with substantial disability and socioeconomic burden. Although pharmacological therapies remain the mainstay of treatment, their effectiveness may be limited by incomplete response and adverse effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive neuromodulatory technique that may modulate cortical excitability and pain-processing networks involved in migraine pathophysiology. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of rTMS compared with sham stimulation in individuals with migraine. Methods: A systematic search was conducted in PubMed (MEDLINE), PsycNet, and Ovid (including MEDLINE and Embase) from database inception to December 2025 in accordance with PRISMA 2020 guidelines. Studies investigating rTMS in adults with migraine and including a sham comparator were eligible for inclusion. Data regarding study design, participant characteristics, rTMS parameters, outcomes, and adverse events were extracted using a predefined template. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Seven studies comprising a total of 301 participants were included. Most trials evaluated high-frequency rTMS targeting the dorsolateral prefrontal cortex. Across studies, rTMS was generally associated with reductions in migraine frequency and severity compared with sham stimulation, although results varied depending on stimulation parameters and study design. Treatment was consistently well tolerated, with only mild and transient adverse effects reported. However, considerable heterogeneity was observed in diagnostic criteria, stimulation protocols, outcome measures, and follow-up duration. Conclusions: Preliminary evidence suggests that rTMS may represent a promising and well-tolerated neuromodulatory approach for migraine management. Nevertheless, methodological variability, limited sample sizes, and concerns regarding risk of bias restrict definitive conclusions. Larger randomized controlled trials with standardized protocols and longer follow-up periods are needed to clarify the clinical role of rTMS in migraine treatment.

Neurology International doi: 10.3390/neurolint18050081

Authors: Peter Jankovič Kamil J. Chodzyński Axel E. Vanrossomme Karim Zouaoui Boudjeltia Andrej Šteňo Christian R. Wirtz Ján Šulaj Andrej Paľa

Background: The risk stratification of unruptured intracranial aneurysms (UIAs) relies largely on static clinical and morphological parameters, which may not fully capture aneurysm-specific wall behavior. ECG-gated four-dimensional computed tomography angiography (4D-CTA) enables the time-resolved assessment of aneurysm wall motion, but reliable interpretation requires the differentiation of biological motion from measurement uncertainty. Methods: In this prospective exploratory pilot study, ECG-gated 4D-CTA was used to evaluate the longitudinal aneurysm size change, global volumetric pulsation (GVP), spatial wall pulsation (SWP), intrinsic wall deformability and variability. Size change and pulsation were defined using predefined resolution- and noise-based thresholds. Spatial wall motion was assessed using phase-resolved three-dimensional displacement maps. Harmonic modeling isolated periodic pulsation, and residual variability exceeding empirically derived uncertainty limits was conservatively interpreted as deformability. Associations with aneurysm growth and ELAPSS scores were analyzed using exploratory statistics. Results: Eleven UIAs in ten patients were followed for 4.3 ± 1.1 years. A longitudinal size change occurred in six aneurysms (54.5%). Baseline GVP was present in eight aneurysms (73%) and SWP in nine (82%). GVP was not associated with a size change (p = 1.00). All aneurysms with a size change exhibited baseline SWP, whereas no size change was observed in aneurysms without SWP; however, this association did not reach statistical significance in this small exploratory cohort (p = 0.18). Conservative variability metrics were not associated with growth but correlated with baseline shape irregularity, particularly the undulation index (Spearman’s ρ up to ~0.90). Conclusions: In this small exploratory pilot cohort, spatial wall pulsation showed a descriptive directional pattern with longitudinal aneurysm size changes, whereas global volumetric pulsation did not. These findings are preliminary, should be interpreted cautiously, and require confirmation in larger, adequately powered longitudinal studies before clinical application.

Neurology International doi: 10.3390/neurolint18050079

Authors: Loredana Mariana Agavriloaei Bogdan Florin Iliescu Gabriela Dumitrița Stanciu Ivona Costachescu Andrei Szilagyi Maria-Raluca Gogu Bogdan Ionel Tamba Mihaela Dana Turliuc

Background: Standardized and ethically compliant animal models remain essential for improving translational research in Alzheimer’s disease. Although Aβ1–42-induced rodent models are widely used, methodological variability continues to limit reproducibility. Methods: We explored the feasibility of a stereotactic intrahippocampal Aβ1–42 rat model established by bilaterally injecting pre-aggregated peptide into the hippocampus of adult Sprague Dawley rats. Model feasibility and targeting accuracy were assessed intraoperatively. Cognitive performance was evaluated using the Y-maze for spatial recognition memory and the novel object recognition (NOR) test. Histological examination was performed using hematoxylin–eosin (H&E) and Congo red staining to assess cytoarchitecture and to provide supportive evidence of amyloid-like deposits. Results: The surgical procedure was well-tolerated, and the injected animals showed reduced performance in behavioural testing, including reduced spatial recognition memory in the Y-maze and decreased discrimination indices in the NOR test. The animals also showed histological changes, including Congo red-positive birefringent structures consistent with amyloid-like congophilic material. Conclusions: This study presents a feasible experimental framework for intrahippocampal Aβ1–42 administration, showing behavioural and histological changes under the present experimental conditions. However, further validation, including sham-operated controls and molecular characterization, will be required before these findings can be interpreted as specific to Aβ-driven pathology.

Neurology International doi: 10.3390/neurolint18050078

Authors: José Alexandre Pereira Frédéric Chantraine Céline Schreiber Tanja Classen Evangelia Agneskis Laurence Medinger Silvia Morini Gilles Areno Xavier Masson Frédéric Dierick

Background: Post-stroke upper-limb spasticity can cause pain, hinder passive care, and lead to secondary musculoskeletal complications. Current minimally invasive treatments have important limitations. Cryoneurolysis, which creates a controlled cold lesion of peripheral nerves, may offer a partially reversible focal denervation alternative. Methods: We conducted a feasibility case series in the outpatient department of a rehabilitation centre. Three adults with chronic post-stroke hemiparesis and a non-functional spastic upper limb underwent ultrasound- and nerve stimulation-guided cryoneurolysis of the musculocutaneous, median, and/or ulnar nerves. All had demonstrated a positive response to diagnostic nerve blocks beforehand. Feasibility outcomes included completion of planned nerve targets, tolerability under local anesthesia, absence of serious adverse events, and completion of 6-month follow-up. Secondary outcomes were Modified Ashworth Scale (MAS), qualitatively assessed passive joint mobility (video-documented), pain measured by visual analogue scale, sensory testing, and electroneuromyography (ENMG). Results: All procedures were completed as planned. Treatment was well tolerated under local anesthesia, and no serious adverse events occurred. MAS decreased by at least 2 points in targeted patterns, with immediate improvement in passive mobility; these effects persisted at 6 months. Pain remained unchanged in two participants and improved in one. Sensory testing at 6 weeks was stable. ENMG findings were heterogeneous, including reduced ulnar sensory action potential amplitude and biceps denervation activity in one participant. Conclusions: In this small series, cryoneurolysis for post-stroke upper-limb spasticity was feasible and associated with sustained tone reduction and improved passive mobility. Larger controlled studies are required to better define safety, optimize targeting strategies, and assess patient-centred outcomes.