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.

Neurology International doi: 10.3390/neurolint18050077

Authors: Berya Günay Samyuktha Ramesh Dhayanand Marijana Matas Vlatka Sotosek Lara Baticic

Acute ischemic stroke (AIS) is characterized by complex interactions among vascular occlusion, endothelial injury, and inflammatory activation, which collectively influence clinical outcomes. Increasing attention has focused on the endothelial glycocalyx, a critical regulator of vascular permeability, mechanotransduction, and inflammatory signaling. Disruption of the endothelial glycocalyx during ischemia and subsequent reperfusion contributes to blood–brain barrier (BBB) dysfunction and secondary brain injury. Mechanical thrombectomy has emerged as the reference standard treatment for large vessel occlusion in AIS. This review synthesizes current evidence on endothelial glycocalyx degradation and associated inflammatory cascades in cute ischemic stroke, with particular emphasis on patients undergoing mechanical thrombectomy. We examine the mechanisms underlying endothelial and BBB injury, ischemia–reperfusion-mediated vascular dysfunction, and systemic inflammatory responses (SIRS). In addition, the potential clinical relevance of circulating biomarkers indicative of endothelial glycocalyx shedding and endothelial damage is discussed. By integrating molecular pathophysiology with contemporary reperfusion strategies, this review highlights the importance of endothelial protection as a potential adjunct to mechanical thrombectomy. While mechanical thrombectomy remains the gold standard therapy for AIS due to large vessel occlusion, targeting endothelial glycocalyx integrity and post-reperfusion inflammation may represent a promising approach to optimizing neurological outcomes and reducing complications. Further research is required to elucidate specific pathophysiological mechanisms and to develop targeted therapeutic strategies aimed at reducing stroke-related morbidity and mortality.

Neurology International doi: 10.3390/neurolint18050076

Authors: Stella Lilles Klari Heidmets Kaisa Teele Oja Karit Reinson Laura Roht Sander Pajusalu Monica H. Wojcik Katrin Õunap Inga Talvik

Background/Objectives: Early-onset epilepsy is associated with a high risk of developing drug-resistant epilepsy (DRE), often manifesting as developmental and epileptic encephalopathies (DEEs). This study aimed to characterize the incidence, syndromes, comorbidities, and etiology of early-onset DRE in Estonia. Methods: This study is a continuation of our earlier nationwide, population-based investigation and included all children with early-onset epilepsy (seizure onset before two years) who developed drug resistance in Estonia between 2013 and 2017 (n = 37). Cases were identified at the country’s only two pediatric neurology departments, ensuring nationwide coverage. Clinical data, electroencephalography, neuroimaging, genetic investigations (chromosomal microarray, single-gene tests, gene panels, exome/genome sequencing), and etiology were analyzed overall and by epilepsy type or syndrome. Results: A total of 37 children with early-onset DRE were included. The incidence of early-onset DRE was 26.5 per 100,000 person-years, peaking in the first year of life (36.1). Drug resistance developed in 43% within six months and 65% within one year. DEEs accounted for 76% of cases, most commonly infantile epileptic spasms syndrome (IESS/West syndrome, 35%). Structural abnormalities were observed in 49% of cases (50% of DEEs), most commonly congenital brain malformations (22%). Pathogenic genetic findings were identified in 41% overall (43% of DEEs). The etiology was established in 78% of children with DRE. Among DEEs, it was found in all Dravet syndrome patients (100%) and 62% of those with IESS/West syndrome. Global developmental delay/intellectual disability occurred in 86%, and motor impairment in 46%. Conclusions: Early-onset DRE, often presenting as DEE, has high incidence, progresses rapidly to drug resistance, and causes substantial comorbidities.

Neurology International doi: 10.3390/neurolint18050075

Authors: Rami Abduljabbar Al-Motassem Yousef Duaa Eid Tamimi Shayma Z. Abdullah Zhenbao Liu

Background: Epilepsy is a chronic disorder with a higher prevalence in low- and middle-income countries. ATP-binding cassette superfamily B1 (ABCB1) not only has a potential influence on the resistance to antiepileptic drugs but also plays a possible role in the occurrence of epilepsy. Purpose: To evaluate the association of ABCB1 polymorphisms, c.1236C>T (rs1128503), c.2677G>T (rs2032582), and c.3435C>T (rs1045642), with epilepsy susceptibility in a Jordanian cohort. Subjects and methods: Eighty-six cases of patients with epilepsy were analyzed using polymerase chain reaction (PCR) for ABCB1 c.1236C>T, c.2677G>T, and c.3435C>T gene variants. The proportions of genotypes and alleles in the epilepsy group were compared with one hundred healthy controls who were previously also analyzed by PCR. Results: The C alleles of the ABCB1 polymorphisms c.1236C>T and c.3435C>T were more prevalent in the epilepsy group than in controls. The patients with epilepsy were less likely to have the TT genotype compared with controls (concerning ABCB1 c.1236C>T) (ORTT vs. CC = 0.42; 95% CI = [0.19–0.91]; p = 0.019). The CC genotype of ABCB1 c.3435C>T was more frequent in epileptics than healthy people (ORCC vs. TT = 4.3; 95% CI = [1.8–9.95]; p = 0.0007). No significant difference in ABCB1 c.2677G>T allelic and genotypic frequencies was observed between epileptic cases and healthy volunteers. Conclusion: Our findings suggest that ABCB1 c.1236C>T and c.3435C>T variants were associated with epilepsy susceptibility in this Jordanian cohort, whereas no significant association was observed for c.2677G>T. These findings should be interpreted cautiously because of the modest sample size and require validation in larger, independent studies.

Neurology International doi: 10.3390/neurolint18040074

Authors: Haohan Wang Zesheng Ying Zhuo Zhi Nijia Zhang Jia Wang Nan Zhang Yingjie Cai Ming Ge

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly aggressive pediatric central nervous system (CNS) malignancies. AT/RT of the lateral ventricle is an exceptionally rare subgroup, with only 11 reported cases. SMARCB1 inactivation is the primary molecular feature of AT/RT. Current consensus is to classify AT/RT based on methylation and molecular profiles into the following subgroups: AT/RT-TYR, AT/RT-SHH, AT/RT-MYC, and a potentially distinct SMARCA4-deficient subtype. AT/RT-MYC exhibits high levels of CD8+ tumor-infiltrating lymphocytes, indicating immunogenic potential. Case presentation: We report three pediatric cases presenting with intracranial hypertension and seizures. Diagnosis was confirmed via histopathology and molecular profiling. Interventions included gross total resection, chemotherapy, radiotherapy, and combined immune checkpoint inhibitors (pembrolizumab and ipilimumab). Outcomes varied from rapid progression to 3-year recurrence-free survival. A cohort of 14 pediatric patients with lateral ventricle AT/RT, comprising 3 institutional cases and 11 cases identified from the PubMed database, was evaluated through a narrative synthesis. Conclusions: These advancements highlight the crucial role of molecular subtyping in tailoring personalized treatments, including epigenetic modifiers and immune-based regimens. However, clinical validation is essential to establish standardized protocols. Integrating genomic, epigenetic, and immune microenvironment profiling may enhance risk assessment and treatment precision, ultimately improving survival and quality of life in pediatric patients.

Neurology International doi: 10.3390/neurolint18040073

Authors: Refat Aboghazleh Shrouq Al-Sabaileh Mustafa Nadi Walid Aburayyan Mohammad Saadaldin Ahiam Awadat Mohammad Badawi Mimas Al-Helalat Afnan Atiyat Manal Udwan Abdel Latif Al-Houwari Abdulraheem Alhourani Abdalraman Al-eyadah Radwan Sabayleh Nesrin Seder

Background: Traumatic brain injury (TBI) has been associated with coagulation disorders, and coagulation and fibrinolytic parameters are frequently monitored in the acute stage of TBI. Methods: Using a rat closed head injury model, mild and severe TBIs were induced. Blood samples were obtained at five post-injury time points, including 1 day and 1, 2, 3, and 4 weeks, to assess coagulation and fibrinolytic parameters, specifically prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, and fibrinogen. Results: In mild TBI, all hemostatic parameters remained largely within physiological ranges, despite minor statistical fluctuations in PT and PTT. Conversely, severe TBI resulted in significant elevations of PT (p = 0.00015) and PTT (p = 0.01) during the first week. Additionally, D-dimer levels increased significantly at week 2 (p = 0.024) and week 4 (p = 0.014) post-injury, surpassing the upper limit of normal. Although fibrinogen levels showed a significant increase at week 2 compared to the control group (p = 0.011), they remained within the normal reference range. Conclusions: While mild TBI is characterized by stable hemostatic markers, severe TBI demonstrates a clear and significant progression from acute coagulation activation to secondary fibrinolysis. These findings suggest that severe TBI-induced coagulopathy is a progressive event requiring extended longitudinal monitoring beyond the initial acute phase.

Neurology International doi: 10.3390/neurolint18040072

Authors: Buşra Kasap Dilek Uludağ Alkaya Nilay Güneş Salih Türk Barış Korkmaz Beyhan Tüysüz

Background/Objectives: Severe neurodevelopmental disorders caused by homozygous ASTN1 variants have recently been reported. The aim of this study is to present the expanded phenotype and prognostic findings through a longitudinal follow-up of a patient with a homozygous ASTN1 variant. Methods: We conducted a 15-year clinical evaluation of a girl who initially presented at 10 years of age. The genetic etiology was investigated using exome sequencing. Results: The patient had a profound intellectual disability, severe expressive language delay, and infantile-onset epilepsy. She also had microcephaly, achieved independent walking at age 7 and had speech limited to only two words at admission. A novel homozygous frameshift variant, c.2096del (p.Cys699Serfs*22), in ASTN1 was identified. Over the follow-up period, her postnatal microcephaly became more pronounced, and she experienced a late relapse into generalized tonic–clonic seizures after a decade-long remission. She remains entirely dependent on caregivers for basic self-care at age 25. Conclusions: ASTN1-related phenotype is associated with a severe neurodevelopmental disease, and the late relapse of seizures after prolonged remission highlights the need for lifelong neurological monitoring and multidisciplinary care.

Neurology International doi: 10.3390/neurolint18040071

Authors: Daniela Ivaldi Gabriele Triolo Roberta Lombardo Carla Susinna Giovanni Restuccia Angelo Quartarone Viviana Lo Buono

Background: Aquatic therapy is increasingly used in post-stroke rehabilitation, but its effects on balance and gait in the chronic phase remain variably reported. This systematic review aimed to evaluate the effects of aquatic therapy, alone or combined with land-based rehabilitation, on balance and gait in individuals with chronic stroke. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted between February and March 2026. Randomized controlled trials enrolling adults with chronic stroke and evaluating aquatic-containing interventions with quantitative balance and/or gait outcomes were included. Owing to clinical and methodological heterogeneity, the primary synthesis was narrative. An exploratory random-effects meta-analysis was additionally performed for post-intervention Berg Balance Scale (BBS) scores. Results: Thirteen randomized controlled trials involving 468 participants were included. Overall, aquatic therapy was associated with more consistent improvements in balance than in gait, while combined aquatic and land-based programs generally showed broader functional gains than land-based rehabilitation alone. In the exploratory meta-analysis, the primary pooled analysis of four studies favored aquatic-containing interventions for post-intervention BBS scores (MD = 3.69, 95% CI 2.69 to 4.69; p < 0.001), with no observed heterogeneity (I2 = 0%). Conclusions: Aquatic therapy may be a useful adjunctive rehabilitation strategy for improving balance in chronic stroke, whereas effects on gait appear more variable. These findings should be interpreted cautiously because the quantitative synthesis was exploratory and the overall evidence base remains heterogeneous and limited by small sample sizes and short follow-up.

Neurology International doi: 10.3390/neurolint18040070

Authors: Filippo Camerota Filippo Mario Topa Giuseppe Di Pietro Federico Zangrando Lorenzo Coluccia Massimiliano Mangone Marco Paoloni Andrea Truini Claudia Celletti

Cerebellar Ataxia, Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS) is a progressive multisystem disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibular failure. Although intensive rehabilitation is commonly recommended, the actual effectiveness and the most appropriate physiotherapeutic strategy for CANVAS have not been clearly established. Background/Objectives: To evaluate the effects of an integrated rehabilitation program combining neurocognitive therapeutic exercise and focal muscle vibration (FMV) on clinical and instrumental measures of gait, balance and postural stability in a CANVAS patient. Methods: A structured protocol consisting of neurocognitive therapeutic exercise and FMV was administered. Clinical measures included the Berg Balance Scale, Tinetti, SARA and SF-36. The instrumental evaluations included stabilometry and gait analysis. Results: The intervention produced improvements in balance scores associated with a reduction in fall risk. Stabilometry revealed reduction in oscillation area. Conclusions: FMV combined with neurocognitive therapeutic exercise may promote clinical and biomechanical improvements in CANVAS.

Neurology International doi: 10.3390/neurolint18040069

Authors: Neriman Ezgin Nikola Šutulović Emilija Djurić Slaviša Milošević Milena Vesković Dušan Mladenović Aleksandra Rašić-Marković Olivera Stanojlović Dragan Hrnčić

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urological disorder characterized by persistent pelvic pain, urinary symptoms, and significant impact on quality of life. In addition to its clinical symptoms, CP/CPPS is frequently associated with psychiatric comorbidities, such as anxiety and depression, indicating complex neurobiological mechanisms. This review explores the mechanisms linking CP/CPPS with affective disorders, emphasizing central nervous system alterations, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and neuroimmune interactions. Evidence in-dicates that central sensitization, microglial and astrocytic activation, and elevated proinflammatory cytokines (IL-1β, IL-6, TNF-α) contribute to maladaptive painemotion network interactions. Additionally, dysregulation of hormones and neurotransmitters may exacerbate both pain perception and mood disorders. Psychosocial factors, including stress, coping strategies, and cognitive-emotional processes, further modulate symptom severity and treatment outcomes, highlighting the importance of a biopsychosocial approach. Gaining a deeper understanding of the neurobiological and psychosocial mechanisms behind anxiety and depression in CP/CPPS can lead to more effective, multidimensional management strategies and enhance patient-centered care.

Neurology International doi: 10.3390/neurolint18040068

Authors: Felix Hess Enayatullah Baki Julian McGinnis Tun Wiltgen Hannah Scholz Kathleen Bernkopf Gerhard Schneider Jan Kirschke Dominik Sepp Bernhard Hemmer Silke Wunderlich Mark Mühlau

Background: Fever occurs frequently in patients with intracerebral hemorrhage (ICH) and is associated with worse functional outcomes. Rapid identification of the fever’s cause is crucial for guiding diagnostics and treatment. Data on the distribution of different fever causes in ICH are limited, and the diagnostic value of the day of fever onset remains uncertain. This study aimed to assess the distribution of fever causes in a large cohort of ICH patients and to evaluate whether temporal patterns of fever onset are associated with its underlying cause in a clinically meaningful manner. Methods: This retrospective single-center study included 547 patients with spontaneous ICH. Fever was defined as a body temperature exceeding 38.3 °C for at least two consecutive days. Fever causes were evaluated by two blinded investigators and categorized as infectious, central, or other causes. Infectious fever causes were further specified. Results: Fever occurred in 213 patients (39%) and was associated with longer hospital and ICU stays (both p < 0.01) and poor functional outcome (odds ratio 2.0, 95% CI 1.1–3.6). The three most frequent fever etiologies (>90% of cases) were pneumonia, central fever, and catheter-associated infections (i.e., urethral tract infections, ventriculitis, and central line-associated bloodstream infections). Median onset day differed across etiologies (overall p < 0.001): central fever developed earliest (2 [IQR 1–3] days), followed by pneumonia (5 [IQR 4–7] days) and catheter-associated infections (8 [IQR 5–12] days). Conclusions: In ICH, the day of fever onset may provide a useful clue to its etiology and could support clinical decision-making, but prospective validation is needed.

Neurology International doi: 10.3390/neurolint18040067

Authors: Michail Vikelis Dimitrios Rikos Andreas A. Argyriou Panagiotis Soldatos Christos Tsironis Emmanouil Giakoumakis Georgia Xiromerisiou Maria Chondrogianni Aikaterini Foska Maria Koutsokera Konstantinos Notas Eleni Mavraki Emmanouil V. Dermitzakis

Objective: This retrospective, intention-to-treat real-world study, designed by the Greek Research Alliance for the Study of headache and Pain (GRASP) sought to compare the effectiveness and safety of anti-CGRP monoclonal antibodies (anti-CGRP Mabs) to topiramate in preventing migraine. Patients and methods: Patients received either fremanezumab, erenumab, galcanezumab, eptinezumab, or topiramate for at least six months. Outcomes included reductions in monthly headache days (MHDs), ≥50% and ≥75% responder rates, monthly acute medication intake (MAI), MHDs with peak headache intensity ≥5 on VAS, migraine-related disability (MIDAS, HIT-6), quality of life (EQ-VAS), discontinuation rates and safety. Results: We included 409 migraine patients (median age 45.2 years), predominantly female (80%) and mostly with long-standing disease and high baseline burden. After six months, all treatments reduced MHDs. Mean MHDs decreased by −7.8 days with anti-CGRP Mabs versus −3.8 days with topiramate (p < 0.001). Higher ≥50% and ≥75% responder rates were observed across all anti-CGRP agents, compared to topiramate. Anti-CGRP Mabs also achieved greater reductions in moderate/severe MHDs, MAI, disability metrics, and superior QOL gains. Among the CGRP-targeted therapies, slight differences in effectiveness outcomes were present, though failing to demonstrate any specific superiority. Safety was favorable for anti-CGRP Mabs, whereas topiramate showed substantially higher adverse events and discontinuations. Conclusions: Anti-CGRP Mabs were more effective, produced greater reductions in disability and higher improvements quality-of-life metrics and were better tolerated than topiramate. Differences among individual anti-CGRP agents were modest and unlikely to represent a clinically meaningful superiority, supporting a class-wide benefit vs. topiramate in migraine prevention both in terms of effectiveness and safety.

Neurology International doi: 10.3390/neurolint18040066

Authors: Alexandra Mihaela Pătrășcan Felix Mircea Brehar Radu Mircea Gorgan Viorel Mihai Prună

Background: In the last few decades, microvascular decompression has been proven to be one of the best therapeutic options in the management of neurovascular compression syndromes, especially trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. However, higher rates of recurrences and morbidities have been recorded postoperatively. In the thorough search for better solutions, the option of adjuvant QEVO® endoscopy has arisen as a very promising alternative. Methods: In this study, a retrospective single-center observational analysis was conducted, comprising patients who underwent microvascular decompression for trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia at our institution, between January 2020 and November 2025. Demographical data and outcomes of therapeutic management were statistically analyzed and presented accordingly. Results: A total of 40 patients diagnosed with neurovascular compression syndromes were neurosurgically treated in our center, and the most common diagnosis was represented by trigeminal neuralgia, identified in 32 patients (80%). Another five (12.5%) patients underwent microvascular decompression for hemifacial spasm, two (5%) patients were treated for combined trigeminal neuralgia and hemifacial spasm, and one patient (2.5%) for glossopharyngeal neuralgia. Arterial conflict was the triggering factor in the majority of cases, and no postoperative mortality was recorded. In patients treated using adjuvant QEVO endoscopy, the identification of hidden conflicts may be facilitated. Furthermore, the use of the QEVO endoscope allowed the identification of additional neurovascular conflicts and influenced intraoperative management in a subset of patients. Conclusions: Notwithstanding the medical literature suggesting that the main influential factor for therapeutic success is the vessel type and the pattern of compression, many authors identified the cornerstone of favorable outcomes as being endoscopic assistance. Nevertheless, this adjuvant factor has had a positive impact on the majority of patients.

Neurology International doi: 10.3390/neurolint18040065

Authors: Giuseppe Magro Oreste Marsico Federico Tosto Concetta Lobianco Laura Rapisarda Giovanni Mastroianni Angelo Pascarella

Organophosphate (OP) exposure can trigger seizures within minutes and can rapidly evolve into status epilepticus (SE). Early seizure generation is plausibly driven by acetylcholinesterase inhibition, leading to central cholinergic overstimulation. With increasing seizure duration, experimental data are consistent with a time-dependent shift toward glutamatergic maintenance (NMDA/AMPA), oxidative stress, neuroinflammation, and progressive failure of GABAergic inhibition. This framework predicts a narrow window in which benzodiazepine (BDZ) monotherapy is most effective and a rising probability of BDZ non-response when seizures are prolonged, while anti-glutamatergic strategies may retain relative efficacy later in the course. This narrative review integrates clinical phenomenology, diagnostic limitations, and mechanistic evidence to propose an operational approach for OP-related seizures and SE in emergency settings. We discuss a pragmatic “Stage 1 Plus” framing for patients presenting after prolonged seizures or in non-convulsive SE with coma. Human evidence remains limited and heterogeneous, and inference is constrained by confounding due to delayed recognition, variable decontamination/resuscitation pathways, sparse EEG confirmation, and selection bias in mass-casualty reporting.

Neurology International doi: 10.3390/neurolint18040064

Authors: Asdrubal Aguilera-Méndez Karel Aguilera-Manuel Alfredo Saavedra-Molina Patricia Ríos-Chávez Santiago Villafaña Renato Nieto-Aguilar Daniel Godínez-Hernández Daniel Ortega-Cuellar Zoraya Palomera-Sanchez Marcia Gauthereau-Torres

Background: Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis, represent a major global health burden and share convergent pathogenic mechanisms, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, calcium imbalance, and neuronal loss. Despite advances in symptomatic management, effective disease-modifying therapies remain limited. Objectives: This review aims to critically synthesize mechanistic, preclinical, and clinical evidence on α-lipoic acid and biotin as candidate neuroprotective agents in neurodegenerative diseases, with emphasis on shared signaling pathways, therapeutic potential, generally favorable safety profiles, and translational limitations. Methods: A narrative and integrative review was conducted, encompassing mechanistic studies, preclinical experimental models, and clinical trials and observational studies evaluating ALA and biotin in neurodegenerative diseases. The evidence was qualitatively analyzed with attention to biological plausibility, consistency across models, and clinical relevance. Results: ALA and biotin modulate key cellular pathways implicated in neurodegeneration, including mitochondrial metabolism, redox homeostasis, inflammatory signaling, and neurovascular function. Preclinical studies consistently report beneficial effects on mitochondrial efficiency, oxidative stress, and neuroinflammatory markers. In contrast, clinical evidence remains heterogeneous, with more extensive evaluation of biotin in progressive multiple sclerosis and more limited or exploratory findings for ALA across neurodegenerative disorders. Conclusions: ALA and biotin exhibit mechanistic convergence across pathways relevant to neurodegeneration and generally favorable safety profiles. Although current evidence supports their biological plausibility as adjunctive or exploratory therapeutic strategies, clinical outcomes remain inconsistent and appear to be influenced by dosing regimens, disease stage at intervention, and endpoint selection. Well-designed clinical studies are required to define their efficacy, optimal dosing, and disease-specific applicability.

Neurology International doi: 10.3390/neurolint18040063

Authors: Salvatore Rinaldi Arianna Rinaldi Vania Fontani

Background/Objectives: Advanced childhood cerebral X-linked adrenoleukodystrophy (cALD) is traditionally regarded as an irreversible terminal phase of neurodegeneration driven by inflammatory demyelination and axonal loss. Experimental evidence indicates that endogenous bioelectrical fields regulate central nervous system organisation, raising the possibility that functional network collapse in cALD may be biologically modifiable, even in the presence of persistent structural damage. This study examined whether longitudinal modulation of endogenous bioelectrical network organisation is associated with sustained clinical and neurophysiological stabilisation in advanced cALD. Methods: We performed a longitudinal observational analysis of two paediatric patients with advanced childhood cerebral X-linked adrenoleukodystrophy undergoing repeated neuroregenerative treatment cycles. Standardised scalp electroencephalography was recorded during spontaneous wakefulness and repeated over months under comparable vigilance conditions. Multimodal analysis included conventional EEG, quantitative EEG, independent component analysis, and standardised low-resolution electromagnetic tomography (sLORETA). Clinical function was assessed using validated measures of consciousness, swallowing, and voluntary motor behaviour. Results: Across patients, longitudinal recordings demonstrated sustained stabilisation of consciousness, swallowing, and voluntary motor function, accompanied by reproducible reorganisation of pathological brain rhythms. Delta and theta oscillations showed a consistent topographical redistribution from limbic–frontoinsular networks towards sensorimotor and parietal integrative cortices. These changes were observed across modalities and timepoints and are unlikely to reflect spontaneous fluctuation, delayed effects of haematopoietic stem cell transplantation, or state-dependent EEG variation. Conclusions: Advanced childhood cerebral X-linked adrenoleukodystrophy is associated with disorganisation of endogenous bioelectrical network activity. In this longitudinal analysis, large-scale network reorganisation was temporally associated with sustained clinical stabilisation, supporting a view of late-stage cALD as a dynamic disorder of network-level vulnerability, rather than a fixed terminal state.

Neurology International doi: 10.3390/neurolint18030062

Authors: Angelka Pešterac-Kujundžić Una Nedeljković Ivana Sretenović Aleksandar Milosavljević Dragoslav Nestorović Vojislav Bogosavljević Ivan Vukašinović

Objectives: Survivors of mild-grade aneurysmal subarachnoid hemorrhage (aSAH) often achieve favorable neurological recovery, yet many continue to experience cognitive difficulties and reduced health-related quality of life (HRQoL). The relative contribution of objectively measured cognition and subjective cognitive complaints to long-term HRQoL in this population remains insufficiently clarified. Methods: This prospective cohort study assessed objective and subjective cognitive functioning one year after mild-grade aSAH (Hunt & Hess I–II) and examined their unique contributions to HRQoL. Forty endovascularly treated aSAH survivors and 80 neurologically healthy controls, matched for sex, age, and educational level, were assessed 12–14 months post-ictus using the Montreal Cognitive Assessment (MoCA), Cognitive Failures Questionnaire (CFQ), and SF-36. Results: Compared with controls, patients demonstrated significantly lower MoCA scores, with cognitive impairment present in 42.5% of cases, as well as reduced HRQoL. In multivariate regression analyses adjusted for demographic, clinical, and affective covariates, subjective cognitive complaints (CFQ) remained independently associated with the mental component summary score of the SF-36 (β = −0.47, p = 0.002). Objective cognitive performance (MoCA) was not associated with the SF-36 component summary scores but showed weaker, domain-specific associations in exploratory analyses. The correlation between MoCA and CFQ was weak (ρ = −0.33), indicating a dissociation between these two measures. Conclusions: One year after mild-grade aSAH, subjective cognitive complaints contribute to mental HRQoL above and beyond the influence of affective symptoms. These findings highlight a clinically relevant dissociation between perceived and objectively measured cognition and support the importance of incorporating patient-reported cognitive difficulties into long-term outcome assessment and rehabilitation planning.

Neurology International doi: 10.3390/neurolint18030061

Authors: Junpei Nagasawa Masamichi Hozumi Tatsuhiro Yokoyama Makiko Ogawa Junya Ebina Mari Shibukawa Takehisa Hirayama Osamu Kano

Background: Anatomical variations in the posterior communicating artery (PCoA) are common, but their association with ischemic stroke remains unclear. In this study, we investigated the relationship between PCoA configuration and the localization of perforator infarction. Methods: We conducted a single-center, retrospective observational study of consecutive patients admitted with acute ischemic stroke between April 2016 and July 2023. Patients with a single, unilateral lacunar infarction confined to the thalamic or lenticulostriate artery (LSA) territory were included. PCoA configuration was assessed using time-of-flight magnetic resonance angiography and dichotomized as present (normal PCoA or fetal-type posterior cerebral artery) or absent (hypoplastic or aplastic PCoA). Using a within-patient, hemisphere-based approach, the presence of PCoA on the infarcted side was directly compared with that on the contralateral side. McNemar’s test with continuity correction was used for laterality analysis. Results: A total of 64 patients met the inclusion criteria, including 45 with LSA infarction and 19 with thalamic infarction. The prevalence of PCoA presence on the infarcted hemisphere was 20.0% in the LSA group and 26.3% in the thalamic group, identical to that observed on the contralateral hemisphere in each group. Within-patient comparisons revealed no significant difference in PCoA presence between infarcted and non-infarcted hemispheres in either territory (all p > 0.05). Conclusions: In patients with unilateral perforator infarction involving the thalamic or LSA territories, PCoA configuration was not associated with infarct laterality. These findings suggest that variations in PCoA anatomy have a limited influence on hemispheric vulnerability to perforator infarction, supporting the predominant role of local small-vessel pathology rather than proximal collateral anatomy in the development of lacunar stroke.

Neurology International doi: 10.3390/neurolint18030060

Authors: Marialuisa Zedde Luigi Cirillo Elisa Francesca Maria Ciceri Nicola Limbucci Mario Muto Mauro Bergui Francesco Causin Rosario Pascarella

Duropathies represent a spectrum of disorders associated with spinal dural tears and cerebrospinal fluid (CSF) leaks. Diagnosis and treatment is often complicated by overlapping clinical manifestations. This review aims to synthesize current literature on duropathies, focusing on their clinical, neuroradiological, and pathophysiological features. A comprehensive literature review was conducted, analyzing various conditions classified as duropathies, including spontaneous intracranial hypotension (SIH), superficial siderosis (SS), spinal cord herniation, and, as added issue, arachnoid webs. The review emphasized the importance of imaging techniques such as MRI and CT myelography in diagnosing these conditions. Duropathies can arise from congenital anomalies, trauma, and degenerative changes, with SIH being characterized by orthostatic headaches and neurological deficits. Imaging typically reveals specific patterns, such as a widened dorsal subarachnoid space and ventral displacement of the spinal cord. Syringomyelia was frequently associated with arachnoid webs, and complications like SS and bibrachial amyotrophy were noted in patients with persistent ventral spinal CSF leaks. The unifying concept of duropathies is proposed, emphasizing the need for timely intervention to mitigate long-term neurological consequences. Enhanced diagnostic strategies are crucial for improving patient outcomes, and a multidisciplinary approach is recommended for the management of these complex disorders. Further research is warranted to clarify the pathophysiological mechanisms underlying duropathies and to establish standardized treatment protocols.

Neurology International doi: 10.3390/neurolint18030059

Authors: Thomas Müller

Background: The term dyskinesia describes involuntary movements of the face, body and extremities. Frequently, they appear following and in relation with prior oral long-lasting and high-dose levodopa therapy in Parkinson’s disease patients. Onset of these motion sequences causes patient distress and caregiver embarrassment with declined quality of life. Continuity of nigrostriatal postsynaptic dopamine receptor stimulation delays occurrence of dyskinesia. A pulsatile pattern with temporary too high dopamine receptor excitation promotes manifestation of dyskinesia. Methods: This narrative review describes past pharmacologic approaches for therapy of dyskinesia, such as the principle of continuous dopamine receptor stimulation. Discussion and Conclusions: Novel concepts were tested. They influenced neurotransmission of serotonin and altered stimulation of dopamine receptor subtypes. The translation of successful experimental research outcomes into valuable clinical trial results with consecutive approval of drugs with a new mode of action under the indication “antidyskinetic” repeatedly failed. An exception is the open-channel blocker of the N-methyl-D-aspartate receptor and dopamine reuptake inhibitor amantadine with its moderate dyskinesia-reducing effects, particularly in its extended-release formulation. This antiviral compound also improves impaired motor behavior and reduces “OFF” intervals. Therefore, amantadine is currently experiencing a certain resurgence in regions where its extended-release formulations are marketed for therapy of levodopa-induced dyskinesia.

Neurology International doi: 10.3390/neurolint18030058

Authors: Hamza Dahshi Marie Varnet Kimberly Goodspeed Jacob Tiller Dallas Armstrong Deepa Sirsi

Introduction: SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) is an epileptic encephalopathy linked to mutations in the SLC6A1 gene and is characterized by early-onset seizures and developmental delays. Despite the growing recognition of SLC6A1 as a major cause of early-onset epilepsy, the electrophysiological changes associated with the disorder remain inadequately characterized. This study aims to identify electrophysiological biomarkers of SLC6A1-NDD by characterizing EEG delta power using automated tools, EEGLAB (v2023.1) and Persyst 13, exploring age- and state-related effects. Methods: We analyzed EEG recordings from 20 patients with SLC6A1-NDD and 20 neurotypical age- and sex-matched controls using EEGLAB and Persyst, quantifying delta power and related metrics. The Wilcoxon signed-rank method tested for differences between patients and controls, area under the curve (AUC) values evaluated patient classifier models, and Pearson’s correlation assessed concordance between EEGLAB and Persyst. Results: Patients with SLC6A1-NDD exhibited significantly elevated delta power (19.4 ± 4.1) compared to controls (14.2 ± 3.0; p < 0.001). The mean delta power showed an age-dependent increasing trend in patients (b = 0.5), contrasting with a decline in controls (b = −1.0; p < 0.001). In Persyst, the frequency of delta activity above an optimized threshold best differentiated patients from controls in wake epochs (AUC = 0.93). Concordance between EEGLAB and Persyst was one-to-one but with moderate variability (R2 = 0.644; p < 0.001). Conclusions: Elevated delta power is a notable feature of SLC6A1-NDD. Cross-platform comparison demonstrates the feasibility of quantitative EEG analysis, while imperfect concordance highlights the need for pipeline standardization. Future work should validate these findings in larger cohorts and, as suitable reference data emerge, benchmark delta power metrics against age-matched children with other developmental and epileptic encephalopathies.

Neurology International doi: 10.3390/neurolint18030057

Authors: Dominika Jakubowicz-Lachowska Magdalena Sarnowska Monika Chorąży Alina Kułakowska

Introduction: Ischemic stroke in young adults is uncommon and is frequently associated with rare etiologies, including autoimmune diseases and vasculitis. Takayasu arteritis (TA) is a chronic inflammatory large-vessel arteriopathy involving the aorta and its major branches and may result in cerebral ischemia due to arterial stenosis or thrombosis. Case Presentation: We report the case of a 26-year-old woman with a history of suspected rheumatoid arthritis and Lyme disease who presented with acute left-sided hemiparesis and dysarthria. At admission, large-vessel vasculitis had not yet been suspected, and the patient was treated according to standard acute stroke protocols. Computed tomography angiography (CTA) revealed occlusion of the right middle cerebral artery bifurcation and the right common carotid artery, with inflammatory changes involving the brachiocephalic trunk and subclavian arteries. Intravenous thrombolysis (iv rtPA) was followed by mechanical thrombectomy (MT), resulting in neurological improvement. Outcome: Further diagnostic work-up confirmed TA, and immunosuppressive therapy with cyclophosphamide and infliximab was initiated. Conclusion: This case underscores the importance of considering inflammatory large-vessel disease in young patients presenting with acute ischemic stroke and illustrates that endovascular reperfusion may be feasible in this clinical setting.

Neurology International doi: 10.3390/neurolint18030056

Authors: Srdjana Telarovic Maja Vrdoljak Pazur Nikolina Zupancic Anamarija Strajduhar Irma Telarovic

Background/Objectives: Kidney transplantation is the standard of care for the majority of patients with end-stage kidney disease. Neurological complications are common, and among them, tremor is very frequent and usually attributed to immunosuppressive drug toxicity. Methods: In this retrospective study, we investigate the incidence and characteristics of tremor in kidney transplant patients and analyze its occurrence with respect to a multitude of demographic and clinical parameters, thereby aiming to confirm the role of calcineurin inhibitor-induced neurotoxicity and to identify other putative predictive factors. Furthermore, we characterize post-transplant tremor with the goal of identifying its clinical features and determining the impact on quality of life. Results: A total of 129 kidney transplant recipients were screened; six patients were excluded due to a history of movement disorders prior to kidney transplantation. In total, 123 patients were included in the final analysis—69 male (56%) and 54 female patients (44%), with a median age of 50. A total of 36% (46 patients) developed tremor in the post-transplant period. Using both univariable and multivariable analyses, we found that female sex and tacrolimus use were independently associated with the development of post-transplant tremor. In addition, multivariable analysis identified an association between younger age and post-transplant tremor. Furthermore, we observed a trend in the duration of symptoms in relation to the calcineurin inhibitor choice. Conclusions: Despite a relatively high prevalence (36%), post-transplant tremor does not significantly impact the QoL and spontaneously resolves within 1 year in adult kidney transplant recipients. Female sex and tacrolimus were identified as independent predictors of post-transplant tremor in renal transplant recipients.

Neurology International doi: 10.3390/neurolint18030055

Authors: Aser Donado-Bermejo Silvia Di-Bonaventura Pablo Barrenechea-Leal Francisco Mercado-Romero Marisa Fernández-Sánchez Raúl Ferrer-Peña

Background: Chronic pain is a prevalent and disabling condition that affects physical health but also cognitive domains. Executive functions, including inhibitory control, cognitive flexibility, and working memory, essentials for self-regulation, treatment adherence, and coping with symptoms, are particularly compromised. Physiotherapy interventions, traditionally aimed at physical outcomes, may also influence executive functions; however, their impact remains unclear. Objective: This review aimed to synthesize current evidence regarding the effects of physiotherapy-related interventions on executive function in adults with chronic pain. Methods: The review followed the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and the protocol was registered in PROSPERO (CRD42024611800). A comprehensive search was performed. Randomized controlled trials (RCTs) included adults with chronic pain (≥3 months) whose executive function outcomes were evaluated after physiotherapy-based interventions. Results: Out of 12,391 records, 10 randomized controlled trials were included. Populations primarily had fibromyalgia, chronic low back pain, and chronic musculoskeletal pain. Interventions encompassed transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS), neurofeedback, structured exercise, and multimodal physical-cognitive-mindfulness training. Intervention durations ranged from one session to 16 weeks. Executive function was assessed with diverse neuropsychological tests. tDCS improved attention, inhibitory control, cognitive flexibility, and working memory. Exercise interventions showed benefits in working memory and inhibitory control. Conclusions: Preliminary evidence suggests that physiotherapy interventions, particularly anodal tDCS and structured exercise, may improve executive functions in individuals with chronic pain. Future trials should incorporate long-term follow-up. Integrating cognitive targets into physiotherapy may enhance the multidimensional management of chronic pain.

Neurology International doi: 10.3390/neurolint18030054

Authors: Maenia Scarpino Antonello Grippo Federica Barraco Benedetta Piccardi Laura Betti Peiman Nazerian Arianna Fabbri Roberto Fratangelo Cristina Mei Andrea Nencioni

Introduction: This study was conducted to determine whether specific emergency physician (EP) diagnoses and/or neurological signs/symptoms upon admission to the Emergency Department (ED) were associated with normal/non-informative emergency electroencephalogram (emEEG). Methods: Data from consecutive patients admitted to the ED of our tertiary hospital over a two-year period (1 January 2023–31 December 2024) were analyzed retrospectively. We evaluated the correlation between normal/non-specific emEEGs and EP admission diagnoses and neurological signs/symptoms on admission. Epileptic discharges and sharp waves with triphasic morphology were considered specific patterns. Results: A total of 2008 patients underwent emEEG recording during the study period. EmEEGs were considered non-informative in 100% of global amnesia diagnoses, 100% of cases of mild head trauma, 100% of cases of migraine with aura, 98.3% of transient ischemic attacks (TIAs), 95.6% of transient losses of consciousness (TLCs) when seizure was not the primary suspected diagnosis, and in 92.7% of falls of unknown dynamics. Epileptic patterns were detected in 4% of patients presenting with TLC and in 2.4% of those with falls of unknown dynamics, with approximately half of these patients having a pre-existing diagnosis of epilepsy. Triphasic waves were detected in 4.9% patients with falls of unknown dynamics, in 1.7% with TIA, and in 0.4% with TLC. All of these patients had fever/sepsis or metabolic/electrolyte disorders. Overall, across all clinical scenarios, emEEGs were considered non-informative in 385 (19.1%) tested patients. Conclusions: emEEGs are almost non-informative in the diagnostic pathway for patients with global amnesia, mild head trauma, and migraine with aura, and in patients with TIA, TLC, or falls of unknown dynamics. EPs can safely consider avoiding emEEGs in the absence of previous epilepsy diagnosis, fever/sepsis, metabolic/electrolyte disturbances, or drug abuse.

Neurology International doi: 10.3390/neurolint18030053

Authors: Christian Messina

Transthyretin amyloidosis (ATTR) is a progressive multisystem disorder characterized by extracellular deposition of misfolded transthyretin fibrils, leading to neurological, cardiac, gastrointestinal, urogenital, sexual, and ophthalmological involvement. While disease-modifying therapies have significantly improved survival and slowed disease progression, a substantial proportion of patients continue to experience a high symptomatic burden that markedly impairs quality of life. Symptomatic manifestations often occur early, may precede the diagnosis, and frequently persist despite etiological treatment. This review provides a comprehensive overview of the symptomatic management of ATTR, with particular emphasis on autonomic dysfunction and its systemic consequences. We discuss current therapeutic strategies for orthostatic hypotension, gastrointestinal dysmotility, nutritional impairment, sexual dysfunction, lower urinary tract dysfunction, and ophthalmological involvement, highlighting both pharmacological and non-pharmacological approaches. Special attention is given to treatment limitations related to cardiac involvement, autonomic failure, and drug tolerability. Despite the clinical relevance of symptom control in ATTR, evidence-based recommendations remain scarce, and no dedicated guidelines currently exist. Most therapeutic approaches are derived from observational studies, expert opinion, and clinical experience. Improved awareness of symptomatic manifestations, early intervention, and a multidisciplinary, individualized approach are essential to optimize patient outcomes. Future research should focus on prospective studies and the development of structured symptomatic treatment algorithms to complement disease-modifying therapies and enhance patient-centered care in ATTR.

Neurology International doi: 10.3390/neurolint18030052

Authors: Gamaliel Wibowo Soetanto Elvan Wiyarta

Background: Chronic subdural hematoma is commonly managed with surgical evacuation when significant mass effect or herniation features are present. Although middle meningeal artery embolization has emerged as an effective adjunctive therapy, evidence supporting its use as standalone treatment in patients with radiological herniation remains limited. Case Presentation: We report a 51-year-old man who presented with a three-week history of progressive headache, intermittent confusion, and mild left-sided weakness. Magnetic resonance imaging demonstrated a right-sided chronic subdural hematoma with marked cortical compression and subfalcine herniation. Despite radiological severity, the patient remained neurologically stable. After multidisciplinary discussion, middle meningeal artery embolization was performed as sole therapy via right radial access using a liquid embolic agent. Selective angiography demonstrated pathological neovascular supply from the right middle meningeal artery, which was completely obliterated following embolization without procedural complications. The post-procedural course was uneventful, with progressive clinical improvement. Follow-up non-contrast computed tomography at eight months demonstrated near-complete resolution of the hematoma with normalization of midline structures, and no surgical evacuation was required. Conclusions: Standalone middle meningeal artery embolization may represent a feasible therapeutic option in carefully selected clinically stable patients with chronic subdural hematoma and radiological herniation features, though further studies are required to define optimal selection criteria and long-term outcomes.

Neurology International doi: 10.3390/neurolint18030051

Authors: Radosław Opiła Karolina Łuczkowska Edyta Paczkowska Przemysław Nowacki Jarosław Peregud-Pogorzelski Bogusław Machaliński

Background/Objectives: Neurotrophins are a family of structurally related growth factors known to play an important role in the physiology and pathophysiology of the central nervous system. In ischemic stroke, lower blood concentrations of brain-derived neurotrophic factor (BDNF) have been linked to worse outcomes. However, data regarding blood levels of other neurotrophins remain limited. Methods: Plasma levels of BDNF, NGF, NT-3 and NT-4 of 93 patients with ischemic stroke were measured using Luminex immunoassay at two time points: within 24 h from onset and on the seventh day. Clinical data regarding co-existing risk factors, National Institutes of Health Stroke Scale (NIHSS) score and mortality were collected and analyzed in relation to analytes. Results: BDNF levels at both time points were lower in patients with severe stroke and correlated negatively with NIHSS scores. No such associations were observed for NGF and NT-3. Patients who died had lower baseline BDNF, NT-4 and higher NT-3. Conclusions: A lower BDNF level, but no other neurotrophins, is associated with worse outcomes in ischemic stroke patients. NT-3 and NT-4 levels change in response to ischemic stroke.

Neurology International doi: 10.3390/neurolint18030050

Authors: Gabriel Burdman Juliet Akkaoui Natalia Colon Andres Perez Madepalli K. Lakshmana

Background/Objectives: Alzheimer’s disease (AD) is defined by amyloid-β plaques and tau neurofibrillary tangles and is typically associated with progressive cognitive decline. However, a substantial subset of individuals remains cognitively intact despite intermediate-to-high AD pathology, a phenomenon termed cognitive resilience. This review aims to synthesize genetic variants and biological pathways associated with preserved cognition in the presence of AD neuropathology. Methods: We performed a narrative thematic synthesis of human genetic studies (GWAS, sequencing, biomarker-informed cohorts) and extreme resilience case reports. Variants were prioritized by replication, mechanistic plausibility, and relevance to clinicopathologic dissociation, and were organized by shared biological pathways. When applicable, cognitive resilience was operationalized using residual-based approaches modeling cognitive performance after adjustment for neuropathological burden, age, sex, and education or cognitive reserve proxies reported by each cohort. Results: Recurrent resilience-associated variants include APOE ε2, APOE3-Christchurch, RELN-COLBOS, ATP8B1, RAB10, PLCG2, PICALM, CLU, FN1, and synapse-linked markers such as NPTX2. These variants converge on lipid metabolism, synaptic function and neuroplasticity, tau regulation and proteostasis, immune and inflammatory signaling, vascular/BBB resilience, and RNA regulation. Conclusions: Genetic determinants of cognitive resilience highlight mechanisms that preserve neural integrity independent of pathological load. Targeting resilience pathways may enable precision therapies designed to maintain cognitive function in AD.

Neurology International doi: 10.3390/neurolint18030049

Authors: Montaha Al-Iede Abdallah Al-Ani Amal Abu Libdeh Amira Masri Ahmad T. Qatawneh Basim Alqutawneh Nihad A. Almasri

Background/Objectives: Our aim was to evaluate sleep quality and the prevalence of OSA among children with CP and other neurological conditions using both polysomnography (PSG) and validated sleep questionnaires. Methods: This study was conducted at the sleep laboratory of the Jordan University Hospital (JUH) between October 2023 and April 2025. Patients were consecutively recruited from pediatric neurology clinics. Patients completed a PSG session, while guardians/caregivers completed the pediatric sleep questionnaire (PSQ) and sleep disturbance scale for children (SDSC) tools on the behalf of the included patients. The cohort was matched with a control group composed of asthmatic children referred for sleep disturbances. Results: We recruited 296 patients, of whom 41.6% had neurological disorders and 58.4% were matched non-neurological controls. Among those with neurological diseases (n = 123), 46.3% were diagnosed with CP. Patients with CP showed significantly lower sleep efficacy than controls (p < 0.001). They also had reduced total sleep time compared to non-neurological controls but, notably, longer sleep time than children with Down Syndrome (all p < 0.05). Patients with CP had arousal index and apnea–hypopnea index values comparable to controls, but both measures were significantly lower than those observed in children with Down Syndrome and other syndromic patients (all p < 0.05). The risk of OSA according to the PSQ was insignificant for both controls and patients with neurological conditions (OR: 0.898; p = 0.720). According to the SDSC questionnaire, patients with neurological conditions had a significantly higher risk of sleep disturbances compared to controls (OR: 2.015; p = 0.043). Conclusion: Patients with neurological diseases are at a higher risk of sleep disturbances compared to controls. This was significantly more apparent in non-CP patients than in those with CP. At present, PSG remains the most objective and reliable tool to evaluate these disturbances.

Neurology International doi: 10.3390/neurolint18030048

Authors: Elisa Duranti Chiara Villa

Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed.

Neurology International doi: 10.3390/neurolint18030047

Authors: Kelly Fisher Eliza Sejdiu Michelle You Rahim Hirani Adam Karp Mill Etienne

Background: In 2024, Reddit, an emerging social media platform, saw a 50% increase in monthly users to nearly 100 million. Reddit has also emerged as a significant space for discussions about health conditions, including epilepsy, which affects about 50 million people globally. Purpose: This study aims to explore trends in the volume, timing, themes, emotional tone, and sentiment of posts on the r/Epilepsy subreddit from 1 December 2023 to 31 December 2024. Methods: We collected 25,222 original English-language posts from r/Epilepsy using Reddit’s Application Programming Interface (API). Data extraction was restricted to English-language submissions to ensure compatibility with sentiment and thematic analyses. We analyzed post volume and timing using chi-square tests and Poisson regression. Emotional tone was measured using TextBlob (version 0.19.0), while compound sentiment scores were calculated via VADER (Valence Aware Dictionary and Sentiment Reasoner) (NLTK version 3.9.1). A Pearson correlation assessed agreement between sentiment and emotional tone, with statistical significance set at p < 0.05. Thematic analysis was conducted using a KMeans clustering algorithm (scikit-learn version 1.6.1) to identify recurring discussion topics. Results: Total monthly posts steadily increased, with the highest number (2175) in December 2024. Peak posts in descending order were in December 2024, August 2024, and November 2024. Posts were not evenly distributed across the week, with a significant peak on Mondays (χ2 = 86.75, p < 0.001) and Poisson regression confirming higher activity early in the week (p = 0.001). Emotional tones fluctuated, with positive sentiments in January and October 2024, and negative sentiments in March and August 2024. KMeans clustering identified five main themes: treatment experiences, community engagement, personal experiences, solidarity, and subreddit gratitude. Manual validation of a random subset of posts demonstrated moderate concordance between automated sentiment classification and human ratings. Conclusions: This study highlights temporal patterns, sentiment dynamics, and thematic structure in online discussions on epilepsy. Social media may offer valuable, real-time insights into patient-centered concerns and community engagement, which can inform healthcare professionals and advocacy groups in supporting individuals affected by epilepsy. Future studies may compare trends of epilepsy discussions across various social media platforms, such as X and Instagram, to further understand online patient experiences.

Neurology International doi: 10.3390/neurolint18030046

Authors: Elpida Stratou Georgia-Nektaria Porfyri Aikaterini Gamvroula Katerina Theodorou Symeon Dimitrios Daskalou Nikolaos Gerosideris Georgia Tsakni Foteini Christidi Anna Tsiakiri Pinelopi Vlotinou Ioanna Giannoula Katsouri

Background/Objectives: Driving performance and competence represent a complex functional domain that may be affected in some individuals with schizophrenia. This scoping review aimed to map existing evidence characterizing driving-related functioning by identifying the cognitive, pharmacological and functional factors that influence driving ability and by synthesizing findings from experimental, neurocognitive and population-based studies. Methods: A structured search of the PubMed, Scopus and ScienceDirect databases was performed in accordance with PRISMA-ScR guidelines to identify studies published between 2015 and 2025 that examined cognitive, pharmacological and functional dimensions of driving in individuals with schizophrenia. Extracted data were narratively and thematically synthesized. Eleven studies met the inclusion criteria. Results: Findings clustered into three domains: cognitive, including attention, executive function, reaction time and visuospatial processing; pharmacological, encompassing drug comparisons, dosage, side effects and treatment stability; and functional, covering license status, driving participation, driving cessation, avoidance behaviors and self-regulation. Conclusions: This review integrates current evidence within a multidimensional and conditional framework, highlighting interactions between cognitive functioning, pharmacological factors, and compensatory self-regulation in individuals with schizophrenia. Understanding these interrelations may inform individualized fitness-to-drive evaluations and contribute to structured, context-sensitive interpretation of driving-related evidence in clinical and regulatory settings.

Neurology International doi: 10.3390/neurolint18030045

Authors: Christopher G. Ballmann Daphne G. Schmid Rebecca R. Rogers Hannah K. Oakes Shelby C. Osburn

Non-motor symptoms (NMSs) are highly prevalent in Parkinson’s Disease (PD) and contribute significantly to disease severity, progression, and diminished quality of life. NMSs are rooted in both physiological and psychological domains and include emotional dysfunction, autonomic dysregulation, cognitive impairment, pain exacerbation, and neural deficits. While pharmacological approaches are often employed for the alleviation of non-motor symptomology, modest efficacy and adverse side effects may limit their practical utility for individuals with PD, leaving the need for the identification of complementary approaches. Music interventions have emerged as potential adjunctive therapeutic approaches that may positively modulate NMSs in both physiological and psychological domains. Physiologically, music interventions have been shown to alter autonomic activity and pain/sensory perceptions and mediate neurotransmitter release related to arousal, physical effort, and stress. Psychologically, music interventions, both passive and active, have been shown to modulate emotional regulation, motivation, attention, and cognitive performance. Emerging evidence utilizing neuroimaging and behavioral techniques further supports this and suggests music-induced benefits even in the presence of advancing neurodegeneration. Overall, findings from this narrative review suggest music may serve as a potential non-invasive adjunctive therapeutic tool to counteract PD-induced NMSs by adaptively modulating physiological and psychological processes. This narrative review aims to gather current evidence on the physiological and psychological mechanisms underlying the benefits of music and proposes potential therapeutic translation for NMSs in PD. Furthermore, current difficulties, gaps in knowledge, and needs for future research are discussed with the goal of informing directions for clinical translation.

Neurology International doi: 10.3390/neurolint18030044

Authors: Sherry Zimmermann Svetlana Blitshteyn

Background: Difficulty swallowing is a common complaint in patients with postural orthostatic tachycardia syndrome (POTS), but there are no qualitative studies that examine dysphagia in patients with POTS, resulting in a significant gap in clinical understanding and research. Methods: A structured interview of patients with autonomic disorders was conducted utilizing the Dysphagia Handicap Index (DHI). Results: Eleven participants (age range 21–71, mean age 46 years, eight women) were selected using purposive sampling through online support communities and referrals from Dysautonomia Clinic. All had POTS, and eight had comorbid Ehlers–Danlos syndrome. The data gathered from participants were used to construct thematic descriptions of their lived experiences. The mean DHI score in this cohort was 4.5, indicating significant impairment in swallowing. Four themes emerged from the participant narratives: (1) the negative physical impact of dysphagia, (2) the negative psychological impact of dysphagia, (3) the impact on daily life and relationships, and (4) reduced healthcare satisfaction. Conclusions: We found significant impairment due to reported dysphagia symptoms in patients with POTS. Further studies are needed to elucidate the pathophysiology, severity and type of dysphagia in POTS and to develop targeted therapies.

Neurology International doi: 10.3390/neurolint18030043

Authors: Muratbek A. Tleubergenov Daniyar K. Zhamoldin Nurzhan A. Ryskeldiyev Aigul D. Tolepbergenova Aisa Z. Nurpeisov Zhanat T. Takenov S. Akshulakov

Background: Primary central nervous system tumours in pregnancy are exceptionally rare, with posterior fossa lesions presenting particular diagnostic and management challenges due to their confined anatomical location and proximity to critical neurovascular structures. Pilocytic astrocytoma (PA), typically a paediatric tumour, is uncommon in adults and exceedingly rare in pregnant patients. The physiological changes in pregnancy can obscure tumour-related symptoms, contributing to diagnostic delay and increased maternal–fetal risk. Methods: We report the case of a 24-year-old pregnant woman at 23 weeks and 5 days’ gestation who presented with progressive neurological deterioration secondary to a cystic mass in the right cerebellar hemisphere. MRI revealed significant brainstem compression and triventricular hydrocephalus. Results: A multidisciplinary team performed an urgent retrosigmoid craniotomy with gross total tumour resection under general anaesthesia and continuous intraoperative fetal monitoring. Histopathology confirmed PA (CNS WHO Grade I). Postoperative recovery was uneventful, and both maternal and fetal outcomes were favourable. Conclusions: This case highlights the importance of early neuroimaging, multidisciplinary coordination, and timely surgical intervention in managing posterior fossa tumours during pregnancy. Although PAs are considered low-grade gliomas, their behaviour in pregnancy can be unpredictable. With careful perioperative planning, neurosurgical treatment can be safely undertaken during gestation, offering optimal outcomes for both mother and fetus.

Neurology International doi: 10.3390/neurolint18030042

Authors: Johnnatas Mikael Lopes Paola Bertuccio Lorenzo Blandi Riccardo Vecchio Anna Odone

Background/Objectives: Subjective cognitive decline (SCD) is an early stage of dementia, although its risk factors remain unclear. We estimated the prevalence of SCD and its associated dementia risk factors in Brazilian adults. Methods: This cross-sectional study is based on data from the second wave (2019–2021) of the Brazilian longitudinal study of aging (ELSI-Brazil) and a nationally representative sample of adults aged ≥50 years. Prevalence of SCD was estimated and defined as self-reported cognitive decline without objective impairment or dementia diagnosis, and the adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated through logistic regression models. Results: Of 6631 participants, 57.5% were women, and 54.4% were non-white, with a mean age of 65.1 years (standard deviation: ±9.70). SCD prevalence was 19.7% (95% CI 18.6–20.9) for a total of 1346 individuals. Significantly strong positive associations with SCD were observed for sociodemographic factors, particularly lower education (OR = 2.79, 95% CI: 2.02–3.85), as well as older age, non-white ethnicity, and lower income (ORs ranging from 1.50 to 1.79). Lifestyle factors, including loneliness and sedentary behavior, showed moderate associations (OR = 1.33 and 1.35, respectively). Among health-related conditions, multimorbidity was significantly associated with higher odds of SCD (OR = 1.40 for ≥3 chronic diseases), with the strongest association observed for hearing loss (OR = 2.29, 95% CI: 1.93–2.71). Diabetes, visual loss, and depressive symptoms showed more modest significant associations (OR 1.25 to 1.31). Conclusions: Our findings support the prioritization of vulnerable populations in public health strategies aimed at promoting healthy ageing and reducing social and health inequalities. Longitudinal studies are needed to clarify whether modifying associated factors may influence SCD trajectories.

Neurology International doi: 10.3390/neurolint18030041

Authors: Alessandro Micarelli Simona Mrakic-Sposta Sandro Malacrida Alessandra Vezzoli Riccardo Xavier Micarelli Beatrice Micarelli Ivan Granito Marco Alessandrini

Background/Objectives: Mild cognitive impairment (MCI) is accompanied by olfactory dysfunction, and few interventions target shared chemosensory–cognitive mechanisms. We retrospectively examined whether a 5-week oxygen–ozone major autohemotherapy (MAH) cycle is associated with coupled improvements in olfactory and cognitive performance in adults with MCI. Methods: We analyzed 81 individuals with MCI who completed 10 MAH sessions (twice weekly) and 93 matched healthy controls. In the MCI group, olfactory function was measured before and after MAH using Sniffin’ Sticks® threshold–discrimination–identification (TDI) scores; global cognition was assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). We evaluated between-group and pre–post changes and used Spearman correlations to assess olfactory–cognitive coupling. Results: At baseline, MCI participants showed lower TDI and MoCA scores than controls and more hyposmia/anosmia. Following MAH, the proportion of normosmic patients increased from 32.1% to 50.6%, with fewer anosmic cases. TDI scores improved but remained lower than in controls. MMSE scores were unchanged, whereas MoCA total scores increased, with domain-level gains and a significant improvement in Language Repetition. TDI gains were modestly correlated with MoCA total and selected domain changes. Conclusions: In this retrospective cohort, MAH was associated with partial restoration improvements of olfactory function and improved cognitive performance. Correlated olfactory–cognitive changes were observed within the treated MCI group; however, causal attribution to O2–O3 MAH cannot be established without randomized, double-blind, sham-controlled trials with coupled olfactory–cognitive gains consistent with a shared, potentially modifiable substrate. Prospective randomized trials are needed to confirm efficacy and clinical utility.

Neurology International doi: 10.3390/neurolint18030040

Authors: Daniel Gonzales-Portillo Bhavya Vashi Kirsten Bains Williams Jorge Cervantes

Purpose: Glioblastoma multiforme (GBM) is a highly aggressive cancer with limited survival despite current treatments. Rising treatment costs highlight the importance of identifying more affordable therapeutic alternatives. A body of literature has shown that metformin has the potential to act as an antineoplastic agent. Here, we examined the effects of metformin on GBM in humans. Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed to perform the review. A total of 469 studies were screened using comprehensive search terms. Of these, 4 studies were compatible for the meta-analysis. Results: Data analysis demonstrated an increase in median overall survival for GBM patients up to 18 months compared to controls (p = 0.00197). Conclusions: Overall, our findings support the efficacy of metformin as an anti-neoplastic agent, and that it may grant a survival advantage for patients diagnosed with GBM. Further analyses should find dose-dependent relationships between metformin and the targeted survival outcomes in larger, rigorous clinical trials.

Neurology International doi: 10.3390/neurolint18020039

Authors: Roberta Grasso Elena Carapelle Maria Eva Terracciano Giuseppe Raunich Antonio Turco Luigi Longo Ciro Mundi

Background: Bilateral optic neuritis is a rare condition generally associated with inflammatory, demyelinating, or toxic causes. Its association with glyphosate exposure has rarely been documented. Case Presentation: A 66-year-old man with hypertension, hypercholesterolemia, and hypothyroidism developed rapid bilateral vision loss within hours after acute inhalational exposure to glyphosate during agricultural work. MRI showed bilateral optic nerve hyperintensity consistent with optic neuritis. Cerebrospinal fluid and serum anti-NMO antibody tests were negative, while visual evoked potentials demonstrated increased latencies. High-dose corticosteroid therapy led to progressive clinical improvement. At follow-up, MRI revealed no new lesions and the patient experienced near-complete visual recovery. Conclusion: This case suggests a possible link between acute glyphosate exposure and reversible bilateral optic neuritis. Early recognition and corticosteroid therapy may support full functional recovery even in severe presentations.

Neurology International doi: 10.3390/neurolint18020038

Authors: Schekeb Aludin Agreen Horr Lars-Patrick Schmill Carmen Wolf Olav Jansen Bodo Kurz Julian Andersson Svea Seehafer Naomi Larsen Patrick Langguth Jens Trentmann

Background/Objectives: Thrombus composition influences the success of endovascular therapy in stroke, but conventional CT is limited in determining it. Spectral-detector-CT (SDCT) can apply material-decomposition and virtual monoenergetic (MonoE) imaging, which may provide a way to gain information on thrombus composition. This experimental study aimed to evaluate the differentiability of heterogeneous thrombi with variable red blood cell (RBC) content using SDCT. Methods: Ten thrombus entities with different compositions on RBC and plasma, thus fibrin content, were manufactured (volumetric RBC%/Plasma% = 90/10; 80/20; 70/30; 60/40; 50/50; 40/60; 30/70; 20/80; 10/90; 5/95) and scanned in an SDCT. Conventional Hounsfield-unit (HU) values, spectral electron density (ED), effective atomic number (Z-effective) and HU in MonoE maps ranging from 40– to 200 keV were evaluated for thrombus differentiation. Results: Conventional HU increased with RBC content, allowing us to differentiate the entities (p < 0.001). ED values also increased with RBC content and allowed for differentiation too (p < 0.001). Z-effective values showed no differences among the different entities (p > 0.05). Regarding the mass-attenuation curves from 40 to 200 keV the different thrombi showed a similar curve progression with highest HU values at 40 and lowest at 200 keV. The thrombi could be distinguished overall at each monoenergetic level by HU (p < 0.001 for each level). The absolute decrease in HU between 40 and 200 keV was thereby not significantly different between the different entities, but the relative decrease was, as it was more pronounced in thrombi with lower RBC content (p < 0.001). Conclusions: Spectral CT enables differentiation between thrombi with different RBC and fibrin contents by means of ED or analysis of the mass-attenuation curve. This offers alternative possibilities that go beyond characterisation based on CT-density alone. The additional inclusion of spectral parameters in thrombus diagnostics could therefore improve diagnosis and treatment.