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.

Neurology International doi: 10.3390/neurolint18020037

Authors: Gonzalo Emiliano Aranda-Abreu Fausto Rojas-Durán María Elena Hernández-Aguilar Deissy Herrera-Covarrubias Luis Roberto Tlapa-Monge Sonia Lilia Mestizo-Gutiérrez

Alzheimer’s disease (AD) is traditionally defined by Amyloid-β (Aβ) plaques and tau neurofibrillary tangles, yet these proteinopathies alone fail to explain disease heterogeneity, progression, and cognitive decline. Emerging evidence identifies chronic neuroinflammation as a central integrator that converts molecular pathology into synaptic failure and neurodegeneration. In this context, Aβ acts as a danger-associated molecular pattern that activates microglial and astrocytic immune programs through receptors such as TREM2, TLRs, and RAGE, leading to inflammasome activation, cytokine release, and oxidative stress. These responses pathologically re-engage developmental complement pathways (C1q–C3–CR3), driving excessive synaptic pruning that correlates more closely with cognitive impairment than neuronal loss. Reactive astrocytes further amplify dysfunction by impairing glutamate and potassium homeostasis, promoting excitotoxic and metabolic stress, while inflammatory glia facilitate prion-like tau propagation via extracellular vesicles. Concurrent neurovascular inflammation disrupts blood–brain barrier integrity and cerebral perfusion, reinforcing immune-metabolic failure. Importantly, neuroinflammatory biomarkers (GFAP, sTREM2, YKL-40, cytokines, complement, and TSPO-PET) provide dynamic readouts of disease activity and therapeutic response. Together, these findings position AD as a disorder of failed immune resolution and support precision immunomodulatory and pro-resolving therapies aimed at restoring neuroimmune homeostasis rather than merely removing protein aggregates.

Neurology International doi: 10.3390/neurolint18020036

Authors: Fabiana Lucà Roberto Ceravolo Michele Massimo Gulizia Sandro Gelsomino Carmelo Massimiliano Rao Nadia Ingianni Giuseppina Vitale Giovanna Geraci Attilio Iacovoni Pietro Scicchitano Adriano Murrone Claudio Bilato Luigina Guasti Furio Colivicchi Fabrizio Oliva Federico Nardi Massimo Grimaldi Iris Parrini

Stroke is a major global health concern, particularly among the elderly, who frequently present with multiple comorbidities, most notably cardiovascular diseases. Importantly, atrial fibrillation confers a nearly fivefold increase in stroke risk and accounts for up to one-quarter of ischemic strokes in older adults. Stroke is a neurological disease characterised by a strong cardiovascular interplay, and its multifactorial nature requires an integrated preventive approach. This review focuses on primary and secondary prevention in this population, with a frailty-informed perspective. We synthesise evidence on blood pressure control, lipid-lowering (including LDL-C targets), glycemic management, and antithrombotic strategies—particularly oral anticoagulation for atrial fibrillation—as well as the role of frailty indices in guiding individualised risk–benefit decisions. We also discuss practical care pathways, including structured post-discharge programs, continuity of care, and the need for multidisciplinary collaboration involving cardiologists, neurologists, and primary care. We highlight how frailty indices refine risk–benefit assessments without justifying therapeutic nihilism, and how sex- and age-related factors shape treatment effectiveness and safety. By narrowing scope and emphasising practical, multidisciplinary prevention strategies, this review aims to support clinicians in reducing recurrent events, disability, and mortality in very old patients. Future work should prioritise pragmatic trials, including those involving the oldest old and the use of standardised frailty metrics, to inform prevention decisions.

Neurology International doi: 10.3390/neurolint18020035

Authors: Álvaro Astasio-Picado Jesus Jurado-Palomo Clara Fátima Rodriguez-Urbaneja

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Neurology International doi: 10.3390/neurolint18020034

Authors: Erin O’Kane Rhiannon De Ivey Katie Pearson Christa Awad Khalifa Mohammed Nathan Williamson Richard Andrew Lumb Ami Mehta Eugene Yee Hing Tang

Background/Objectives: Stroke survivors require life-long secondary prevention to reduce recurrence, but they also often face long-term impairments that may limit medication adherence (MA) including cognitive, physical, and psychological effects. This updated qualitative meta-synthesis aims to descriptively explore and synthesise the experiences and perspectives of stroke/TIA survivors, informal and formal carers of stroke survivors, and healthcare professionals involved in post-stroke/TIA care, with a focus on factors influencing and hindering MA. Methods: A qualitative meta-synthesis was conducted in accordance with PRISMA guidance. Searches were undertaken across MEDLINE, CINAHL, Embase, PsycINFO, Scopus and Web of Science for studies published from 1 January 2018. Study quality was assessed using the Joanna Briggs Institute checklist and data synthesised using Thomas and Harden’s method. Results: Of 5463 titles and abstracts screened, 212 underwent full-text review with 13 papers meeting inclusion criteria from eight countries with a total of 435 participants. Seven key themes were identified: knowledge and understanding, beliefs and attitudes, practical barriers, social support, healthcare system, psychological factors and medication characteristics. Survivors showed a varied understanding of their condition and prescribed medicines, with unclear communication often contributing to confusion. Beliefs and attitudes shaped adherence, ranging from confidence in treatment to scepticism. Practical barriers included financial costs, physical impairments, and limited access to services. Social support from family, friends, and healthcare professionals was also important. Psychological wellbeing, coping strategies, and medication side effects further influenced adherence, highlighting the challenges faced by this patient group. Conclusions: Medication adherence post-stroke/TIA is shaped by multiple complex factors including knowledge, beliefs, attitudes, and lived experience. As a descriptive synthesis of qualitative evidence, these findings do not permit conclusions regarding causality or intervention effectiveness but provide insight into perceived barriers and facilitators that may inform future intervention development and clinical questioning.

Neurology International doi: 10.3390/neurolint18020033

Authors: Todd D. Rozen Katelyn A. Bruno Ethan M. Rozen Frances C. Wilson Marysia S. Tweet Raymond C. Shields Sharonne N. Hayes Dacre R. T. Knight Shilpa N. Gajarawala Sukhwinder J. S. Sandhu Alok A. Bhatt DeLisa Fairweather

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia in patients with hypermobile Ehlers–Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD) who presented to an academic headache clinic. Methods: This is a retrospective cohort study. We used an electronic medical record to look for all patients seen at the Mayo Clinic Florida Headache Center and EDS Clinic between 2019 and 2025 with a diagnosis of hEDS or HSD and neuroimaging of both the intracranial and cervical arteries. Results: There were 103 patients who met the inclusion criteria. There was no statistically significant difference between hEDS and HSD patients in developing cerebral/cervical arterial anomalies. Of the sample, 95% of the hypermobile patients with abnormal neuroimaging also had migraine. A total of eleven (10.7%) patients (hEDS + HSD) were diagnosed with unruptured intracranial aneurysms. Trends included age less than 50 years, small aneurysms in the anterior circulation, and having migraine with aura. Five (4.8%) patients were diagnosed with spontaneous cervical artery dissection with trends for HSD, over the age of 50 years, vertebral artery involvement and a history of migraine without aura. Six (5.8%) patients were diagnosed with fibromuscular dysplasia with trends for HSD, over the age of 50 years, carotid artery involvement and a history of migraine with aura. Conclusions: This is the first study to identify that patients with the more common type of EDS, HSD and hEDS, and a possible concomitant history of migraine have a heightened risk for the development of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia. Our findings suggest the need for targeted screening with intracranial and extracranial arterial imaging for this unique patient population.

Neurology International doi: 10.3390/neurolint18020032

Authors: Agnieszka Wiertel-Krawczuk Zofia Krawczuk Juliusz Huber

Background/Objectives: To date, few studies have reported the use of neurophysiological testing to assess the long-term progression of functional changes in median and ulnar nerve conduction in children and adolescents with mucopolysaccharidosis (MPS). This case series study aimed to perform an electroneurographic (ENG) assessment of the median and ulnar nerves in three young patients with MPS treated with enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) over a five-year observation period. Methods: Bilateral electroneurography of the motor and sensory fibers in the median and ulnar nerves, recording compound muscle action potential (CMAP) and sensory nerve action potential (SNAP), was performed twice in 5-, 7-, and 19-year-old males at two time points: before and five years after the application of ERT and HSCT. Results: In three MPS patients with Hurler or Hunter syndrome, ENG studies similarly demonstrated decreased amplitudes and prolonged distal latencies in their CMAP recordings, confirming the bilateral progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves. The SNAP recordings revealed more severe degenerative processes of similar types in the sensory fibers of the median nerves. Nerve conduction studies in the ulnar nerve fibers bilaterally revealed analogous pathologies, but with a lesser degree of progression. Conclusions: This study confirms the progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves, which were associated with decreased amplitudes and prolonged distal latencies in the CMAP recordings of the MPS patients. More expressed degeneration processes of a similar type were found in the sensory fibers of the median nerves. Ulnar nerve pathologies of neural conduction are less advanced in patients with Hurler and Hunter syndromes. It seems advisable to implement neurophysiological diagnostics as soon as possible to specify surgical or conservative therapy, which is crucial for maintaining hand function in the case of progressive peripheral neuropathies in patients with MPS. The timing of the treatment and the patient’s age may be factors influencing the effectiveness of treatment.

Neurology International doi: 10.3390/neurolint18020031

Authors: Fernando Reyes Camila Parker Tania Turquie Aldo Chimal Lorermy Villalobos Frida Bailey Antonio Ibarra Igor Lavrov Carlos A. Cuellar

Background: Central cord syndrome (CCS) is the most common incomplete spinal cord injury, producing more severe motor deficits in the upper than lower extremities and impairing sensory and autonomic function. Although transcutaneous spinal cord stimulation (tSCS) has shown benefits in motor and sensory recovery after spinal cord injury, studies have not explicitly documented whether CCS subjects were included. The aim of this study was to assess the effects of tSCS over 12 weeks on motor and sensory outcomes in a subject with CCS. Methods: A 20-year-old male with a C7 injury was evaluated at baseline and after 12 weeks with the American Spinal Cord Injury Impairment scale, Modified Ashworth Scale, Penn and Spasm Frequency Scale, 3-Meter Walk Test and 6-Minute Walk Test, 9-Hole Peg Test, Box and Block Test, hand dynamometry, and lower-limb EMG. tSCS was applied between T9 and L1 at 30 Hz. Results: At 12 weeks, upper-limb motor and sensory scores improved, while spasm frequency and hand spasticity were reduced. Manual dexterity improved bilaterally in the 9-Hole Peg and Box and Block Tests, with a 2 kg gain in right-hand grip strength. In the 6-Minute Walk Test, the distance covered increased from 224.4 m to 295.2 m, and a 1.36 s reduction in 3-Meter walking time was achieved. Conclusions: tSCS improved motor and sensory function and reduced spasticity and spasms. These findings suggest that tSCS may serve as an effective complementary intervention for motor and sensory rehabilitation in individuals with mild cervical injuries, including CCS.

Neurology International doi: 10.3390/neurolint18020030

Authors: Anatoli Pinchuk Nikolay Tonchev Anna Schaufler Claudia A. Dumitru Belal Neyazi Klaus-Peter Stein I. Erol Sandalcioglu Ali Rashidi

Background/Objectives: Postoperative intracerebral hematomas (POHs) are a common complication following brain tumor surgery and are typically associated with unfavorable outcomes. While extensive hemorrhages have been studied extensively, smaller, Non-Space-Occupying hemorrhages are frequently detected, yet their clinical relevance and associated risk factors remain insufficiently understood. This study aimed to identify predictive factors for the occurrence of Non-Space-Occupying postoperative cerebral hemorrhages in patients undergoing brain tumor resection. Methods: A total of 1481 patients without a history of anticoagulant or antiplatelet therapy underwent brain tumor surgery at our neurosurgical institute over a ten-year period. Non-Space-Occupying postoperative hemorrhages were diagnosed in 84 patients using cranial computed tomography (cCT) or magnetic resonance imaging (cMRI) performed after the tumor resection. Demographic data, pre-existing comorbidities, and tumor characteristics were collected and analyzed. Results: Non-Space-Occupying POHs occurred in 5.6% of patients. The most frequent tumor type associated with POHs was glioblastoma multiforme (N = 33; 39.3%), followed by metastatic lesions (N = 9; 10.7%) and benign primary intracranial neoplasms (N = 31; 38%). None of the affected patients exhibited new neurological deficits or signs of increased intracranial pressure. A multivariate analysis identified the tumor size as an independent risk factor for Non-Space-Occupying POHs (p = 0.002), with patient age emerging as the strongest predictor (p = 0.001). Conclusions: Non-Space-Occupying POHs after a brain tumor resection are significantly associated with the tumor size, an advanced patient age, and the presence of pre-existing liver disease. The recognition of these risk factors may facilitate targeted perioperative monitoring and guide postoperative management strategies.

Neurology International doi: 10.3390/neurolint18020029

Authors: Małgorzata Wiszniewska Urszula Włodarczyk Mariusz Domagalski Artur Słomka Inga Dziembowska Maciej Gawrysiak Anna Żdanowicz Ewa Żekanowska

Background/Objectives: Protein Z (PZ) and the protein Z-dependent protease inhibitor (ZPI) are vitamin K-dependent regulators of coagulation that inhibit activated factor Xa. Their relevance in ischemic stroke (IS) remains insufficiently characterized, with inconsistent evidence regarding their association with stroke severity and outcomes. This study aimed to evaluate the concentrations and dynamics of PZ and ZPI in the acute phase of IS in patients treated with intravenous thrombolysis or conservative therapy and to assess their potential prognostic significance. Methods: Eighty-four patients with acute IS were enrolled and divided into two groups: group I treated with intravenous thrombolysis (rt-PA) and group II managed conservatively. PZ and ZPI concentrations were measured using ELISA on admission (day 1) and on day 7. Associations with factor X activity, the modified Rankin Scale (mRS), and the National Institutes of Health Stroke Scale (NIHSS) were analyzed using nonparametric tests and Spearman correlations (p < 0.05). Results: PZ concentrations were significantly higher in thrombolysis-treated patients than in conservatively managed patients both on day 1 (median: 2810.05 vs. 2178.50 ng/mL; p = 0.024) and day 7 (2982.90 vs. 2286.50 ng/mL; p = 0.026). A slight negative correlation between PZ and mRS on day 7 was observed in the conservative group (r = −0.360; p = 0.043). In thrombolysis-treated patients with dyslipidemia, PZ increased from day 1 to day 7, whereas it decreased in those without dyslipidemia. No significant correlations were found between PZ, ZPI, or factor X and NIHSS or ASTRAL scores. Conclusions: Higher PZ concentrations in the acute phase of IS—particularly in rt-PA-treated patients—may reflect differences related to the timing of the acute ischemic process and reperfusion status, suggesting potential utility as markers of stroke severity or outcome.

Neurology International doi: 10.3390/neurolint18020028

Authors: Jesus Antonio Lara-Reyes Cristofer Zarate-Calderon Gonzalo E. Aranda-Abreu Luis I. García Fausto Rojas-Durán

Background: Neuropathic pain represents a substantial global burden with limited effective therapeutic options. Pulsed Electromagnetic Field (PEMF) therapy has emerged as a potential non-invasive adjuvant, though clinical evidence remains inconsistent. This systematic review and meta-analysis evaluated PEMF efficacy and safety, specifically analyzing the influence of etiology and stimulation parameters. Methods: Following PRISMA 2020 guidelines (PROSPERO: CRD420251184151), five databases (Cochrane, PubMed, Scopus, Web of Science, and LILACS) were searched for Randomized Controlled Trials (RCTs) comparing PEMF versus sham. Risk of bias was assessed via Cochrane RoB 2, and heterogeneity was explored through detailed subgroup analyses. Results: Thirteen RCTs met the inclusion criteria (N = 688). While global analysis indicated a statistically significant pain reduction (SMD: −1.01; p = 0.03), it exhibited extreme statistical heterogeneity (I2 = 92.8%) and instability. After adjusting for missing studies using the Trim-and-Fill method, global significance disappeared. However, subgroup analysis resolved this inconsistency, revealing a massive, clinically meaningful effect in Spinal/Radicular pain (SMD: −2.35; 95% CI: −4.42 to −0.29), whereas Peripheral Neuropathy showed no significant reduction (SMD: −0.38; 95% CI: −0.86 to 0.10). Conclusions: The PEMF evidence base for neuropathic pain is currently highly fragmented. Extreme heterogeneity and publication bias render “one-size-fits-all” efficacy estimates invalid and potentially misleading. Instead, our data reveals a critical etiological divergence: PEMF appears highly effective for spinal/radicular pathology, likely due to the mechanical nature of the lesion, but demonstrates limited efficacy for diffuse peripheral neuropathy. Future research must abandon generic protocols in favor of etiology-specific trials, prioritizing high-frequency parameters and rigorous bias control.

Neurology International doi: 10.3390/neurolint18020027

Authors: Eun Hae Kwon Julia Steininger Antonia Bieber Saskia Kools Teresa Kleinz Lovis Hilker Lea Ebner Louisa Ortmann Louisa Basner Christiane Schneider-Gold Ralf Gold Raphael Scherbaum Kalliopi Pitarokoili Lars Tönges

Background: In Parkinson’s disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction studies were performed on 13 patients with multiple system atrophy (MSA) and 9 patients with progressive supranuclear palsy (PSP) at baseline. PNP was diagnosed according to standard electrophysiological criteria after exclusion of common secondary causes. Comprehensive clinical evaluation included motor and non-motor assessments over two years of follow-up. Results: At baseline, PNP was present in 53.8% of MSA patients and 66.7% of PSP patients. MSA patients with PNP showed greater motor symptom severity (UPDRS III score; p = 0.046) and worse cognitive performance (MoCA; p = 0.044) compared to those without PNP. Over two years, a significant reduction in the tibial nerve amplitude was observed exclusively in MSA patients (p = 0.039), paralleling disease progression. Conclusions: This study provides the first longitudinal evaluation of clinical and electrophysiological PNP progression in MSA and PSP. A high comorbidity of PNP in patients with APS could contribute to motor and sensory impairments in these patients. Our findings indicate that PNP progression may reflect disease progression in MSA. Given the limited sample size, larger-scale longitudinal studies are needed to further investigate biomarker potential of PNP in APS and to clarify differences in peripheral nerve involvement between synucleinopathies and tauopathies.

Neurology International doi: 10.3390/neurolint18020026

Authors: Andrea Demeco Rosa Cristina Bruno Raffaele Bonfiglio Lorenzo Mancini Federica Pisani Lorenzo Scozzafava Chiara Conte Antonio Ammendolia Alessandro de Sire Nicola Marotta

Background: Parkinson’s disease (PD) is characterized by motor disturbances that significantly impact balance, gait, and quality of life. Personalized Rhythmic Auditory Stimulation (pRAS) is an emerging rehabilitative approach that utilizes auditory entrainment to improve step and gait control. The aim of this systematic review is to critically summarize the data from the most recent evidence concerning the use of pRAS in gait rehabilitation for patients with Parkinson’s disease. Methods: A systematic review was conducted following PRISMA guidelines, including records that evaluated music-based or technological interventions based on personalized RAS. Primary outcomes included spatiotemporal gait parameters and distance covered. Results: Ten studies were included in the analysis. All the studies reported clinically relevant improvements: increases in gait speed, step length, and amplitude. Moreover, a reduction in freezing of gait episodes (up to 36%), greater walking distance, and good adherence were reported. Conclusions: Personalized, adaptive, or on-demand solutions proved more effective than traditional forms of cueing. Moreover, the available evidence suggests that pRAS constitutes an effective and safe rehabilitative option for gait disturbances in PD. However, further studies with larger sample sizes and prolonged follow-up periods are necessary to evaluate its long-term impact and transferability into clinical practice.

Neurology International doi: 10.3390/neurolint18020025

Authors: Oana Vrînceanu Rodica Bălașa Smaranda Maier Luigi Pontieri Melinda Magyari

Background: Environmental factors are known to influence the clinical presentation of patients with multiple sclerosis. This study aims to compare the demographic and clinical characteristics of multiple sclerosis patients treated at two diverse geographical settings. Methods: A cross-sectional, observational cohort study was conducted in two MS centers: the Danish Multiple Sclerosis Center (DMSC) in Copenhagen, Denmark and the Regional MS Center in Târgu Mureș, Romania. We compared patients’ demographic and clinical characteristics between MS centers, including sex distribution, current age, MS onset age, latest EDSS scores, symptomatology at disease onset, MS phenotype and type of ongoing DMT. Results: In both cohorts, sex distribution was similar, with females constituting 69.2% in DMSC, and 65.7% in Târgu Mureș. Pyramidal symptoms at MS onset were predominant among Targu Mures patients (32.7%), while sensory symptoms were more frequent among DMSC patients (33%). Progressive forms of MS were more prevalent in Târgu Mureș (22.6%) compared to DMSC (9.9%). High-efficacy DMTs were on use by 58.3% patients in DMSC and only by 29.4% patients in Târgu Mureș, who were mostly on low-efficacy DMTs (54.4% vs. 12.4% in DMSC). Conclusions: The study highlights both shared and distinct characteristics of MS patients treated in these two centers. These findings underscore the importance of regional considerations in the management and treatment of MS.

Neurology International doi: 10.3390/neurolint18020024

Authors: Raffaele Falsaperla Vincenzo Sortino Cristina Malaventura Silvia Fanaro Elisa Ballardini Aloise Martina Annamaria Sapuppo Agnese Suppiej

Background: Neonatal hypoxic–ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and ketone bodies have emerged as potential adjunctive neuroprotective interventions. This scoping review aims to critically evaluate the mechanistic rationale, preclinical evidence, and clinical feasibility of ketogenic approaches. Methods: A scoping review of the literature was conducted, including experimental and clinical studies investigating ketogenic diets, endogenous ketosis, and exogenous ketone supplementation in neonatal hypoxia–ischemia. Evidence was synthesized across mechanistic, preclinical, nutritional, and clinical domains, with particular attention to developmental context, timing of intervention, safety considerations, and translational relevance in the contest of therapeutic hypothermia. Results: Preclinical studies consistently demonstrate that ketone bodies enhance cerebral energy metabolism, support mitochondrial function, reduce excitotoxic signaling, and attenuate oxidative stress and neuroinflammation in the immature brain. Neonatal models show preferential utilization of β-hydroxybutyrate over glucose during hypoxic–ischemic stress, suggesting intrinsic metabolic advantages. Emerging evidence also supports potential long-term effects on epigenetic regulation and white matter development, although direct causal validation in neonatal HIE remains limited. Nutritional studies indicate that carefully monitored enteral and parenteral feeding is feasible in critically ill neonates, identifying a potential window for metabolic interventions. Conclusions: Ketogenic strategies represent a plausible, multimodal approach to targeting the metabolic and inflammatory sequelae of neonatal HIE. While current evidence is insufficient to support clinical implementation, this scoping review provides a hypothesis-generating framework to guide future translational research and the design of carefully controlled clinical trials in neonatal neurocritical care.

Neurology International doi: 10.3390/neurolint18020023

Authors: Sara Eyal Shira Alfasi Karin Ben Zaken Ibrahim O. Sawaid Lior Segev Samuel Mesfin Pnina Frankel Rahaf Ezzy Trishna Saha-Detroja Shilpa Madhavan Naamah Bloch Baruh Polis Abraham O. Samson

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD.

Neurology International doi: 10.3390/neurolint18020022

Authors: Pavol Skacik Lucia Kotulova Ema Kantorova Egon Kurca Stefan Sivak

Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, frequently associated with visual and oculomotor disturbances. Quantitative analysis of eye movements represents a non-invasive method for assessing central nervous system dysfunction beyond conventional imaging; however, the diagnostic and predictive value of oculomotor metrics remains insufficiently defined. Objectives: The aims of this study were to compare smooth pursuit gain and reflexive saccade parameters (latency, velocity, and precision) between individuals with MS and healthy controls, and to evaluate their ability to discriminate disease status. Methods: This cross-sectional study included 46 clinically stable patients with MS (EDSS ≤ 6.5) and 46 age- and sex-matched healthy controls. Oculomotor function was assessed using videonystagmography under standardized conditions. Group differences across horizontal and vertical gaze directions were analyzed using linear mixed-effects models. Random forest models were applied to assess the discriminative performance of oculomotor parameters, with permutation-based feature importance and receiver operating characteristic (ROC) curve analysis. Results: Patients with MS showed significantly reduced smooth pursuit gain across most horizontal and vertical directions compared with controls. Saccadic latency was significantly prolonged in all tested movement directions. Saccadic velocity exhibited selective directional impairment consistent with subtle medial longitudinal fasciculus involvement, whereas saccadic precision did not differ significantly between groups. A random forest model combining pursuit and saccadic parameters demonstrated only moderate discriminative performance between MS patients and controls (AUC = 0.694), with saccadic latency contributing most strongly to classification. Conclusions: Quantitative eye-movement assessment revealed widespread oculomotor abnormalities in MS, particularly reduced smooth pursuit gain and prolonged saccadic latency. Although the overall discriminative accuracy of oculomotor parameters was limited, these findings support their potential role as complementary markers of central nervous system dysfunction. Further longitudinal and multimodal studies are required to clarify their clinical relevance and prognostic value.

Neurology International doi: 10.3390/neurolint18020021

Authors: Tomislav Felbabić Rok Berlot Maja Trošt Dejan Georgiev Mitja Benedičič

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated with deep brain stimulation, although this remains an experimental treatment. Methods: In this two-case report we present the first two cases of patients with Gilles de la Tourette syndrome in Slovenia treated with deep brain stimulation of the anteromedial globus pallidus internus. Results: Over an 18-month follow-up period, we observed an improvement in both cases. In the first case, the Yale Global Tic Severity Scale score decreased from 71 (17 for motor tics, 14 for phonic tics, and 40 on the impairment scale) to 44 points (12 motor, 12 phonic, and 20 impairment). In the second case, the score decreased from 72 (16 motor, 16 phonic, and 40 impairment) to 38 points (8 motor, 10 phonic, and 20 impairment). Conclusions: Deep brain stimulation could be a promising treatment for this disorder. However, further research is needed to determine the most suitable patients and targets.

Neurology International doi: 10.3390/neurolint18010020

Authors: Stephanie Q. Liang Daniel M. Oh Fawaz Philip Tarzi Nerses Sanossian David S. Liebeskind Jeffery L. Saver Melissa Wilson Roy A. Poblete

Background: The management of spontaneous intracerebral hemorrhage (ICH) has centered around controlling blood pressure in order to prevent hematoma expansion (HE). Rate-pressure product (RPP) has emerged as a hemodynamic marker that accounts for heart rate (HR) and systolic blood pressure (SBP), both of which are crucial in modifying shear stress to the vasculature. We hypothesized that RPP in the pre-hospital hyperacute phase is positively associated with initial hematoma volume and HE. Methods: We analyzed 263 patients with primary ICH from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study with initial and interval neuroimaging. RPP was calculated as the product of HR and SBP in pre-hospital and pre-treatment phases, stratified into quintiles. HE was defined by volume expansion of >6 mL or >33% from baseline volume on repeat neuroimaging performed within 48 h of the first scan. The primary outcome was the initial hematoma volume by quintiles of hyperacute RPP. The secondary outcome was the occurrence of HE across RPP quintiles. Multivariable logistic regression was used to assess the degree to which RPP affects HE. Results: Of the 263 patients analyzed, 116 (44%) had HE. The proportion of patients with HE or the initial hematoma volume was not statistically significant across RPP quintiles overall. HE was significantly more common in female patients or patients on anticoagulation. Conclusions: Elevated RPP was not associated with increased initial hematoma volume or subsequent HE in the hyperacute period after spontaneous ICH. Future research is necessary to determine the clinical importance of RPP as a biomarker in the clinical outcome of ICH.

Neurology International doi: 10.3390/neurolint18010019

Authors: Farhan Ishaq

Background: Sleep-disordered breathing (SDB) and intracerebral hemorrhage (ICH) share a bidirectional relationship: SDB may increase ICH risk, while ICH can induce or exacerbate SDB. However, the prevalence and characteristics of post-ICH SDB remain poorly defined. Objective: To estimate the prevalence of SDB among ICH survivors and examine associated clinical factors, including the relative burden of obstructive (OSA) versus central sleep apnea (CSA). Methods: A systematic review and meta-analysis were performed across PubMed, Scopus, CINAHL, and ClinicalTrials.gov. Studies assessing SDB in adults with ICH using American Academy of Sleep Medicine (AASM) category 1–4 diagnostic devices were included. Random-effects models estimated pooled prevalence at varying apnea–hypopnea index (AHI) thresholds, with subgroup analyses by setting, timing, geography, and diagnostic factors. Results: Seventeen studies met inclusion criteria. Pooled SDB prevalence was 85% (95% CI: 80–91%) at AHI > 5, with 49% (95% CI: 42–57%) experiencing moderate SDB (AHI > 15), and 21% (95% CI: 15–27%) experiencing severe SDB (AHI > 30). The prevalence of OSA predominated 73% (95% CI: 64% to 82%),while CSA occurred in 5% (95% CI: 2–9%), corresponding to a pooled RR of 7.44 and OR of 53.08 for OSA versus CSA. Conclusions: SDB—primarily OSA—is highly prevalent following ICH, underscoring the need for early, routine screening and intervention to improve neurological and cardiovascular outcomes.

Neurology International doi: 10.3390/neurolint18010018

Authors: Efthalia Angelopoulou Sokratis Papageorgiou John Papatriantafyllou

Background/Objectives: Dementia represents a growing public health challenge. The WHO Global Action Plan on the Public Health Response to Dementia emphasizes early detection, risk reduction, and innovation as key priorities. Mild Behavioral Impairment (MBI), defined as the emergence of persistent neuropsychiatric symptoms in older individuals, represents a potential marker of early neurodegeneration and possible window for early intervention. This review explores the role of MBI in dementia prevention, mapping current evidence within the WHO Global Action Plan framework. Methods: A comprehensive search was performed in PubMed, Scopus, and the official WHO website, during 1 September 2025–10 November 2025, without time restrictions. Eligible sources included original clinical studies, reviews, and policy documents addressing MBI, dementia prevention, and public health. Data were thematically synthesized according to the seven objectives of WHO: (1) dementia as a public health priority, (2) dementia awareness and friendliness, (3) dementia risk reduction, (4) dementia diagnosis, treatment, care and support, (5) support for dementia carers, (6) information systems for dementia, and (7) dementia research and innovation. Results: Accumulating evidence indicates that MBI assessment can capture early behavioral manifestations of neurodegenerative and other forms of dementia, correlating with fluid, neuroimaging and genetic biomarkers. Integrating MBI screening through the easy-to-administer MBI Checklist (MBI-C) into clinical and community-based care, including telemedicine pathways and research, may enhance early identification and personalized interventions, enrich the pool for clinical trials, and facilitate research in biomarker and therapy. MBI-related research further supports its integration in remote digital monitoring and population-based prevention. Conclusions: Embedding MBI-informed screening and interventions into national dementia strategies aligns with WHO objectives for early, equitable and scalable prevention and brain health.

Neurology International doi: 10.3390/neurolint18010017

Authors: Alisar Katbe Ismaïla Diagne Gilbert Bernier

Late-onset sporadic Alzheimer’s disease (LOAD) is the most common form of dementia. The disease is characterized by progressive loss of memory and behavioral changes followed by neurodegeneration of all cortical areas. While the contribution of genetic and environmental factors is important, advanced aging remains the most important disease risk factor. Because LOAD does not naturally occur in most animal species, except humans, studies have traditionally relied on the use of transgenic mouse models recapitulating early-onset familial Alzheimer’s disease (EOAD). Hence, the development of more representative LOAD models through reprograming of patient-derived cells into neuronal, glial, and immune cells became a necessity to better understand the disease’s origin and pathophysiology. Herein, and focusing on neurons, we review current work in the field and compare results obtained with two different reprograming methods to generate LOAD patient’s neuronal cells: the induced pluripotent stem cell and induced neuron technologies. We also evaluate if these models can faithfully mimic cellular and molecular pathologies observed in LOAD patients’ brains.

Neurology International doi: 10.3390/neurolint18010016

Authors: Alexander von Hessling Tim von Wyl Dirk Lehnick Chloé Sieber Justus E. Roos Grzegorz M. Karwacki

Background: Simulation-based training may offer a useful approach to support skill acquisition in neurointerventional stroke treatment without exposing patients to procedural risks. As the global demand for thrombectomy rises, training strategies that ensure procedural competence while addressing workforce constraints are increasingly important. With this pilot study, we aim to generate a hypothesis as to whether additional exposure of trainees to mechanical thrombectomy could benefit from simulator training on top of the standard training carried out on flow models. This study was designed as an exploratory pilot investigation and was not able to provide inferential or confirmatory statistical conclusions. Methods: Six novice participants (advanced clinical-year medical students with completed anatomical and preclinical training, but without previous exposure to catheter-based interventions) performed two neurointerventional tasks, vascular access and mechanical thrombectomy (MTE), on flow models. After a baseline assessment, three participants received standard model-based training (control group), and three received additional simulator training using a high-fidelity angiography simulator (Mentice VIST G5). Performance was reassessed after four weeks using technical and clinical surrogate metrics, which were ranked and descriptively analyzed. Results: No relevant differences were observed between groups for the vascular access task. In contrast, the simulator group demonstrated a trend toward improved performance in the MTE task, with greater gains in efficiency, autonomy, and procedural safety. Conclusions: Our findings indicate a possible benefit of even brief simulator exposure for skill acquisition for complex endovascular procedures such as MTE. While conventional training may suffice for basic skills, simulation may be particularly helpful in supporting learning in more advanced tasks.

Neurology International doi: 10.3390/neurolint18010015

Authors: Foad Alzoughool Loai Alanagreh Yousef Aljawarneh Haitham Zraigat Mohammad Alzghool

Background: Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin’s association with neurological diseases and its underlying mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle–Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. Results: Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher α-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-β pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin αVβ5/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. Conclusions: Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation.

Neurology International doi: 10.3390/neurolint18010014

Authors: Annamaria Leone Luna Digioia Rosita Paulangelo Nicole Brugnera Luciana Lorenzon Fabiana Montenegro Pietro Fiore Petronilla Battista Stefania De Trane Gianvito Lagravinese

Background/Objectives: Post-traumatic epileptogenesis is a frequent and clinically relevant consequence of traumatic brain injury (TBI), often contributing to worsened neurological and functional outcomes. In patients experiencing early post-injury seizures, rehabilitative strategies that support recovery while considering increased epileptogenic risk are needed. This case study explores the potential benefits of combining neurofeedback (NFB) with motor therapy on cognitive and motor recovery. Methods: A patient hospitalized for severe TBI who experienced an acute symptomatic seizure in the early post-injury phase underwent baseline quantitative EEG (qEEG), neuromotor, functional, and neuropsychological assessments. The patient then completed a three-week rehabilitation program (five days/week) including 30 sensorimotor rhythm (SMR) NFB sessions (35 min each) combined with daily one-hour motor therapy. qEEG and clinical assessments were repeated post-intervention and at 6-month follow-up. Results: Post-intervention qEEG showed significant reductions in Delta and Theta power, reflecting decreased cortical slowing and enhanced neural activation. Relative power analysis indicated reduced Theta activity and Alpha normalization, suggesting improved cortical stability. Increases were observed in Beta and High-beta activity, alongside significant reductions in the Theta/Beta ratio, consistent with improved attentional regulation. Neuropsychological outcomes revealed reliable improvements in global cognition, memory, and visuospatial abilities, mostly maintained or enhanced at follow-up. Depressive and anxiety symptoms decreased markedly. Motor and functional assessments demonstrated meaningful improvements in motor performance, coordination, and functional independence. Conclusions: Findings suggest that integrating NFB with motor therapy may support recovery processes and be associated with sustained neuroplastic changes in the early post-injury phase after TBI, a condition associated with elevated risk for post-traumatic epilepsy.

Neurology International doi: 10.3390/neurolint18010013

Authors: Frédéric Chantraine José Alexandre Pereira Céline Schreiber Tanja Classen Gilles Areno Frédéric Dierick

Background: Chronic post-stroke spasticity often limits gait despite best-practice botulinum-toxin intramuscular injections (BTIs), whose benefit is constrained by short duration, dose ceilings, and tachyphylaxis. Cryoneurolysis (CNL) induces a reversible axonotmesis with preserved endoneurium, potentially providing longer tone reduction with fewer adverse effects, but its impact on whole-gait quality and its compatibility with implanted functional electrical stimulation (FES) remain poorly documented. Case presentation: A 43-year-old man, 12 years after right middle cerebral artery stroke, walked independently with an implanted common peroneal FES system but complained of effortful gait with left-knee “locking” and drop foot without FES. Multiple BTI series to triceps surae and quadriceps yielded only transient benefit. Two ultrasound-guided CNL sessions targeted tibial (soleus, medial gastrocnemius) and femoral (rectus femoris, vastus intermedius) motor branches. Quantitative gait analysis and fine-wire electromyography (EMG) were performed at baseline, 6 weeks after each CNL, and at 6 months, with and without FES. CNL produced immediate and sustained reductions in triceps surae and quadriceps overactivity, resolution of genu recurvatum, normalization of stiff-knee gait, improved ankle dorsiflexion, and increased swing phase knee flexion (>50°). Gait Deviation Index rose from 69 to 80 and Gillette Gait Index decreased by more than 50%, with preserved strength and without adverse events. Conclusions: Targeted, sequential CNL of tibial and femoral motor branches can safely deliver durable, clinically meaningful gait improvements when BTI has reached its ceiling and can act synergistically with implanted FES. Quantitative gait analysis and EMG sharpen clinical decision-making in spasticity management.

Neurology International doi: 10.3390/neurolint18010012

Authors: Anke K. Jaekel Manuel Pickermann Ann Katrin Walter Anna-Lena Butscher John Bitter Franziska I. Winterhagen Ruth Kirschner-Hermanns Stephanie C. Knüpfer

Background/Objectives: Patients with acute severe neurological disorders often receive a transurethral indwelling catheter (TUIC) during their initial treatment. These TUICs often remain in place until the transfer to a rehabilitation or a long-term care facility. There are no systematic concepts for bladder management and no data regarding the impact on the catheter associated, health-related quality of life (HRQoL) in this patient group. The aim of this study was to investigate the impact of successful TUIC removal on the HRQoL of those affected and to contribute to the development of systematic bladder management. Methods: A prospective longitudinal study was conducted on 33 patients treated at a neurological rehabilitation centre due to acute severe neurological disorders. The HRQoL was assessed using the SF-36 Health Survey prior to and following the TUIC removal. The influence of urinary incontinence was analysed. The mean differences were determined using a one-sample t-test adjusted for age and gender. Results: TUIC removal was successful in 61.8% (21/33). The SF-36 Health Survey showed the following improvements (adj. mean diff., 95% CI, p-value): Mental Component Summary measure (4.36, 0.34; 8.38, p = 0.035), Role-Emotional (20.89, 0.54; 41.24, p = 0.045), Physical Functioning (10.03, 3.18; 16.88, p = 0.007). The comparison between incontinent and continent patients showed a poorer HRQoL for the incontinent group. Conclusions: Successful TUIC removal has a positive influence on psychological/emotional aspects and physical functioning. Structured bladder management that considers the physical and psychological aspects of patients and nursing staff, as well as medical and economic aspects, should be pursued with vigour.

Neurology International doi: 10.3390/neurolint18010011

Authors: Riwaj Bhagat

Patent foramen ovale (PFO) is present in roughly one quarter of adults and is over-represented among younger patients with cryptogenic ischemic stroke. The past decade has produced compelling evidence from randomized trials showing that PFO closure is beneficial than medical therapy in preventing recurrent ischemic stroke in appropriately selected patients. Despite this, anticoagulation continues to be used when closure is not feasible, declined, contraindicated, or considered after recurrent events. The observation that some patients experience “breakthrough” stroke or transient ischemic attack (TIA) despite therapeutic anticoagulation raises a critical question: why does medical therapy fail in PFO-associated stroke, and why does closure appear superior? This narrative review synthesizes the latest evidence on the pathophysiology of PFO-associated stroke, with attention to mechanisms that remain incompletely addressed by anticoagulation. It analyzes randomized trial data comparing antiplatelet therapy, anticoagulation, and transcatheter closure. It examines the role of high-risk PFO anatomical characteristics, the Risk of Paradoxical Embolism (RoPE) score, and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification in understanding medical therapy failure. Additionally, the review explores whether PFO “type” predicts anticoagulation failure and highlights future research directions needed to further optimize therapy. In conclusion, in appropriately selected patients with high-risk PFO features, closure provides greater stroke risk reduction than medical therapy alone, albeit with small absolute risk differences and a procedural risk of atrial fibrillation.

Neurology International doi: 10.3390/neurolint18010010

Authors: Jordana Mariane Neyra Chauca Manuel de Jesús Ornelas Sánchez Nancy García Quintana Karen Lizeth Martín del Campo Márquez Brenda Areli Carvajal Juarez Nancy Rojas Mendoza Martha Ayline Aguilar Díaz

Background: Aging is traditionally characterized by progressive structural and cognitive decline; however, increasing evidence shows that the aging brain retains a remarkable capacity for reorganization. This adaptive neuroplasticity supports cognitive resilience—defined as the ability to maintain efficient cognitive performance despite age-related neural vulnerability. Objective: To synthesize current molecular, cellular, neuroimaging, and electrophysiological neuromarkers that characterize adaptive neuroplasticity and to examine how these mechanisms contribute to cognitive resilience across aging. Methods: This narrative review integrates findings from molecular neuroscience, multimodal neuroimaging (fMRI, DTI, PET), electrophysiology (EEG, MEG, TMS), and behavioral research to outline multiscale biomarkers associated with compensatory and efficient neural reorganization in older adults. Results: Adaptive neuroplasticity emerges from the coordinated interaction of neurotrophic signaling (BDNF, CREB, IGF-1), glial modulation (astrocytic lactate metabolism, regulated microglial activity), synaptic remodeling, and neurovascular support (VEGF, nitric oxide). Multimodal neuromarkers—including preserved frontoparietal connectivity, DMN–FPCN coupling, synaptic density (SV2A-PET), theta–gamma coherence, and LTP-like excitability—consistently correlate with resilience in executive functions, memory, and processing speed. Behavioral enrichment, physical activity, and cognitive training further enhance these biomarkers, creating a bidirectional loop between experience and neural adaptability. Conclusions: Adaptive neuroplasticity represents a fundamental mechanism through which older adults maintain cognitive function despite biological aging. Integrating molecular, imaging, electrophysiological, and behavioral neuromarkers provides a comprehensive framework to identify resilience trajectories and to guide personalized interventions aimed at preserving cognition. Understanding these multilevel adaptive mechanisms reframes aging not as passive decline but as a dynamic continuum of biological compensation and cognitive preservation.

Neurology International doi: 10.3390/neurolint18010009

Authors: Xianghong Meng Kequan Zhou

Background: Standard ketogenic diets (KD) and fish oil have established efficacy for drug-resistant epilepsy (DRE), but adherence and variability remain challenging. Objective: The objective of this study is to provide the first systematic evaluation of clinical evidence for emerging dietary interventions for epilepsy—specifically those other than standard KD and fish oil—and to rigorously evaluate their effectiveness and certainty of evidence to address the current gap in dietary management literature. Unlike prior reviews focused on standard KD or carbohydrate-modified versions, this study is the first to synthesize evidence for “non-standard” interventions—including olive oil-based KDs, probiotics, and restrictive gluten/glutamate-free diets—which are typically excluded from traditional dietary meta-analyses. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, Cochrane, and Google Scholar up to March 2025. Randomized Controlled Trials (RCTs) and Non-Randomized Studies of Interventions (NRSIs) were included, with quality assessed using RoB 2 and ROBINS-I tools. Results: Eight studies (total n = 675) were identified, comprising 2 RCTs and 6 NRSIs. These included olive oil-based KDs (n = 1), probiotic/synbiotic supplementation (n = 2), medium-chain triglyceride (MCT) additions (n = 2), and gluten-free (n = 1) or glutamate-free (n = 1) diets. Evidence quality is generally low, with 75% of studies at high risk of bias. Preliminary responder rates reached 83.1% in uncontrolled olive oil-based KD studies, whereas the only RCT evaluating a low-glutamate diet showed no significant seizure reduction (p = 0.57). Conclusion: Evidence for emerging dietary interventions beyond standard KD is nascent and of low certainty. Interpretation: While preliminary signals exist for olive oil-based KDs and probiotics, current data are insufficient for clinical recommendation; this review identifies these as promising exploratory targets requiring validation through rigorous, blinded RCTs.

Neurology International doi: 10.3390/neurolint18010008

Authors: Regev Cohen Adi Hersalis Eldar Yaron River Ofir Schuster Zina Baider Shelly Lipman-Arens Yael Galnoor Tene Linor Ishay Lamis Mahamid Olga Feld Simon Nina Avshovitch Alvira Zbiger Eran Diamant Amram Torgeman Elad Milrot Ofir Israeli Shlomo Shmaya Itzhak Braverman Shlomo E. Blum

Background: Botulism is a rare but potentially fatal neuroparalytic illness caused by Clostridium botulinum neurotoxins (BoNTs). While adult cases usually result from foodborne exposure or wound infection, intestinal colonization is exceedingly uncommon. Diagnosis can be delayed by overlap with other neuromuscular syndromes, and confirmation requires specialized assays. Anti-GQ1b antibodies, classically associated with Miller–Fisher syndrome (MFS), have rarely been reported in confirmed botulism, raising questions about shared pathophysiology. Case Presentation: We describe an adult patient with acute dyspnea, xerostomia, and cranial neuropathies. No foodborne source was identified, but intestinal colonization of BoNT/B toxigenic Clostridium botulinum was confirmed by stool enrichment and mouse lethality bioassay. The patient improved promptly following heptavalent antitoxin. Unexpectedly, anti-GQ1b antibodies were detected during recovery, a finding typically linked to MFS rather than botulism. Discussion: This case illustrates the diagnostic challenges of sporadic cases of botulism, especially when respiratory compromise and autonomic dysfunction dominate the initial presentation. The autoantibodies finding raises the possibility of molecular mimicry, whereby toxin–ganglioside interactions expose neuronal epitopes and trigger an immune response. While causality cannot be proven, the overlap between botulism and GQ1b-positive neuropathies merits further investigation. Conclusions: Clinicians should maintain high suspicion for botulism in adults with acute dyspnea, especially when associated with cranial neuropathies, even in the absence of foodborne exposure. Anti-ganglioside antibodies in this context should be interpreted with caution, as they do not exclude botulism but may highlight immunological overlap with autoimmune neuropathies.

Neurology International doi: 10.3390/neurolint18010007

Authors: Samskruthi Madireddy Sahithi Madireddy

Tourette syndrome (TS), or Tourette’s, is a tic disorder (TD) belonging to a group of neuropsychiatric conditions marked by recurrent motor movements or vocalizations known as tics. TD, including TS, typically begins in childhood between 4 and 18 years of age and affects approximately 3% of children and adolescents. The etiology and pathogenesis of TD are multifactorial, involving genetic, immunologic, psychological, and environmental factors. Evidence suggests that neurotransmitter dysregulation, particularly within the cortical dopaminergic networks of the basal ganglia and limbic system, which support motor control and cognition, may be involved in the development of TD. Nutritional factors may modulate TD through various mechanisms, including effects on neurotransmitter synthesis and metabolism, neurodevelopment, neural architecture, and neuroimmune activity. This review integrates current evidence on the roles of vitamins D, B6, and A, as well as iron, magnesium, zinc, and copper, in TD. For each micronutrient, its physiological and neurobiological functions are discussed, along with possible mechanistic links to TD pathophysiology. Additionally, we summarize the impact of nutrient deficiencies and assess available evidence regarding their potential therapeutic potential role in TD management. Overall, this synthesis highlights how nutritional status may influence TD onset and symptom severity, suggesting that nutrient-based interventions could potentially serve as valuable adjunctive strategies in treatment.

Neurology International doi: 10.3390/neurolint18010006

Authors: Ana Lesac Brizić Branislava Popović Tina Zavidić Nevena Todorović Verica Petrović Nataša Pilipović-Broćeta Ana R. Miljković Aleksandar Ljubotina Ema Dejhalla

Background/Objectives: Beyond respiratory problems, COVID-19 can cause a variety of symptoms, such as neurological disorders caused by biological and psychological factors. Brain fog (BF), a post-illness cognitive impairment that many patients report, can be evaluated with reaction time (RT) testing. Response latency is measured by RT, which can be either simple (sRT) or complex (cRT). This study focuses on how COVID-19 affects cognitive function, with particular attention on RT changes, BF prevalence, and implications for daily life. Methods: The study included 599 participants from Bosnia and Herzegovina, Croatia and Serbia. RT was measured using PsyToolkit and participants completed a COVID-19-associated BF questionnaire. Participants who experienced BF after their latest COVID-19 infection rated its severity using a visual analogue scale (VAS). Additional clinical data were obtained from medical records. Results: BF was reported by 40% of participants post-COVID-19. Men reported it less frequently but found it more disruptive. RT progressively declined post-infection, reaching peak impairment at 15 weeks, following recovery, with RT normalizing by six months. Conclusions: COVID-19 is linked to temporary RT impairment, peaking at 15 weeks post-infection and resolving by six months, independent of BF presence. This study emphasizes the need for a biopsychosocial approach to BF management. Easily available RT assessments should be incorporated into routine clinical practice.

Neurology International doi: 10.3390/neurolint18010005

Authors: Ting He Xu Wang

Background/Objectives: The circadian regulator, circadian locomotor output cycles kaput (CLOCK), is well-established in maintaining sleep–wake rhythms, yet its cell-type-specific functions in sleep regulation remain largely unexplored. While ventromedial hypothalamic (VMH) prodynorphin (PDYN)-expressing (VMHPDYN+) neurons are known to modulate homeostatic and motivational processes, their potential role in circadian sleep regulation has not been investigated. Methods: To address this, we developed mice with PDYN neuron-specific functional suppression of CLOCK activity (mClkΔ19) by interfering with their internal clock through Adeno-Associated Virus (AAV)-mediated overexpression of dominant-negative CLOCKΔ19 in PDYN-Cre mice. Results: We found that mClkΔ19 mice exhibited reduced locomotor activity during the dark phase, earlier activity peaks, and impaired rhythmicity of rapid eye movement (REM) and non-REM (NREM) sleep. Sleep analysis in mClkΔ19 mice showed selective reductions and fragmentation of light-phase REM sleep, more frequent sleep–wake transitions, and shorter REM cycles during the dark phase, indicating disrupted REM sleep timing. EEG spectral analysis in mClkΔ19 mice revealed decreased gamma activity during REM sleep in the light phase and an increase in delta activity coupled with decreased gamma during wakefulness in the dark phase. Conclusions: These findings suggest that the CLOCK activity in VMHPDYN+ neurons is vital for circadian accuracy, REM sleep stability, and brain oscillations during sleep–wake cycles.

Neurology International doi: 10.3390/neurolint18010004

Authors: Hisaka Kurita Junya Murata Kazuki Ohuchi Yuichi Hayashi Masatoshi Inden

Primary Brain Calcification (PBC) is a neurodegenerative disorder of unknown etiology that results in bilateral calcifications within the brain. PBC symptoms vary, including Parkinsonian symptoms and psychiatric symptoms. Abnormalities in phosphate metabolism within the brain are hypothesized to be a mechanism underlying the onset of PBC, but the precise pathophysiological mechanism remains unclear. Furthermore, no fundamental treatment or therapeutic agent for PBC has been established. Previous studies have reported SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, JAM2, CMPK2, and NAA60 as causative genes for familial PBC. Elucidating the pathophysiological mechanisms of PBC and developing treatments and therapeutic agents requires appropriate experimental disease models. Knockout mice and mutant mice targeting familial causative genes have been reported to be useful as in vivo models of PBC. Furthermore, several disease-specific iPS cells for PBC have been reported, suggesting their potential utility as PBC models. This paper reviews each familial causative gene and current PBC models, including genetically modified animals and disease-specific iPS cells, and examines their usefulness for understanding disease mechanisms and advancing therapeutic research.

Neurology International doi: 10.3390/neurolint18010003

Authors: Takafumi Tanei Satoshi Yamashita Satoshi Maesawa Yusuke Nishimura Tomotaka Ishizaki Yoshitaka Nagashima Takahiro Suzuki Hajime Hamasaki Shun Yamamoto Toshihiko Wakabayashi Ryuta Saito

Background/Objectives: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are effective injectable medications for the treatment of migraine. This study aimed to evaluate continuation, resumption, and withdrawal rates of CGRP-mAb treatment under real-world clinical conditions. Methods: Treatment-naïve patients with at least 3 months of follow-up after starting CGRP-mAb treatment were included. The decision to continue, discontinue, or resume CGRP-mAb treatment was made freely by the patients. Headache Impact Test-6 (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ) were administered before starting treatment and one month after each CGRP-mAb injection. The endpoints were as follows: continuation rates of CGRP-mAb treatment after treatment initiation; resumption rate; withdrawal rate; changes in HIT-6 and MSQ scores; and differences in background factors between the resumption and withdrawal groups. Results: Of the 1162 migraine patients, 146 were included in the analysis. Continuation rates of CGRP-mAb treatment at 3, 6, 9, 12, 18, and 24 months were 93.2%, 80.2%, 68.9%, 58.8%, 55.4%, and 51.7%, respectively. For the patients who discontinued, the resumption rate was 76.8%, and the withdrawal rate was 20.7%. HIT-6 and MSQ scores were significantly decreased at all assessment points compared with before CGRP-mAb treatment. There were no significant differences in factors between the resumption and withdrawal groups. Conclusions: Under real-world clinical conditions in which patients were free to choose their own treatment, the continuation rate of CGRP-mAb treatment 12 months after treatment initiation was 58.8%, and more than half of patients remained on treatment after 24 months. The resumption rate was 76.8% and the withdrawal rate was 20.7%.

Neurology International doi: 10.3390/neurolint18010002

Authors: Victor M. Rivera

Multiple sclerosis (MS) affects approximately 2.9 million people in the world, exerting a significant economic and societal burden. The disease is increasingly identified among populations considered as uncommonly affected. MS is reported in all regions of the World Health Organization (WHO) member states in Africa, the Americas, South-East Asia, Europe, the Eastern Mediterranean and the Western Pacific, affecting all ethnicities while exhibiting substantially variable prevalences. Countries with high MS prevalence and some with moderate frequencies generally have economically better structured healthcare systems. Nevertheless, health disparities in these countries are accentuated by suboptimal accessibility of care for their minorities, immigrants and other underserved populations. Social Determinants of Health (SDOH) might have an impact on morbidity and higher rates of disability. Large segments of the world population (i.e., African, Latin American, people from the Middle East and Southeast Asia) do not have access to adequate MS diagnostic procedures, compounded by reduced availability of neurologists. Healthcare disparities exist practically in every country of the world. Active wars and a large number of refugees resulting from conflict augments the challenges to healthcare systems. These global factors constitute obstacles to the adequate management of MS. A collective international path is required to facilitate access to highly effective, albeit onerous treatments, some already approved and being utilized, i.e., monoclonal antibodies and B-lymphocyte depletory agents, and others foreseen in the future as advanced therapeutic molecules continue to develop.

Neurology International doi: 10.3390/neurolint18010001

Authors: Elena Suleymanova Anna Karan

The blood–brain barrier (BBB) is essential for maintaining cerebral homeostasis, and its dysfunction is increasingly recognized as an active driver of epilepsy. This review explores the mechanisms by which BBB disruption contributes to seizures and the development of chronic epilepsy. Potentially epileptogenic insults, including traumatic brain injury, stroke, and status epilepticus, induce acute and often persistent BBB leakage. This breach permits the extravasation of serum albumin, which activates transforming growth factor-beta (TGF-β) signaling in astrocytes. This cascade leads to astrocytic dysfunction, impaired potassium buffering, neuroinflammation, and synaptic remodeling, collectively fostering neuronal hyperexcitability. Furthermore, BBB disruption facilitates the infiltration of peripheral immune cells, amplifying neuroinflammation and propagating a pathologic cycle of BBB damage and seizure activity. BBB damage is mediated by multiple processes, including the activation of the plasminogen activation (PA) system. Furthermore, these processes of BBB disruption and neuroinflammation provide a shared pathological basis for neuropsychiatric disorders like depression and anxiety, which are common comorbidities of epilepsy, through shared mechanisms of neuroinflammation and neurovascular unit (NVU) dysregulation. BBB dysfunction can also contribute to the resistance to antiepileptic drugs. Finally, we discuss the therapeutic potential of stabilizing the BBB as a viable strategy for developing disease-modifying therapies for epilepsy.

Neurology International doi: 10.3390/neurolint17120207

Authors: Urvish Patel Neel Patel Mahika Khurana Akshada Parulekar Amrapali Patel Juan Fernando Ortiz Rutul Patel Eseosa Urhoghide Anuja Mistry Arpita Bhriguvanshi Mohammed Abdulqader Neev Mehta Kogulavadanan Arumaithurai Shamik Shah

The journal retracts the article, “Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke—A Cross-Sectional Study of NHANES” [...]

Neurology International doi: 10.3390/neurolint17120205

Authors: Ayidh Saad Alharthi Chafik Ibrahim Hassan Ali Alsayed Alsharkawy Saeed Dhaifallah Saeed Alzahrani Saif Ahmed Alzahrani

Background/Objectives: Scheie syndrome is the attenuated phenotype of mucopolysaccharidosis type I (MPS I), a lysosomal storage disorder resulting from partial deficiency of α-L-iduronidase. The attenuated clinical spectrum and absence of cognitive impairment often delay recognition. Early manifestations may mimic common pediatric conditions, leading to repeated evaluations without a definitive diagnosis. Methods: We describe a 12-year-old girl who presented with slowly progressive bilateral hand stiffness, weak grip strength, and intermittent sensory symptoms over one year. Her initial investigations—including laboratory studies, electrophysiology, imaging, and multispecialty evaluations—were unremarkable. Results: The gradual progression of symptoms involving joints, motor function, and vision prompted metabolic testing. Whole exome sequencing revealed a homozygous IDUA variant, and enzymatic testing confirmed markedly reduced α-L-iduronidase activity, establishing the diagnosis of Scheie syndrome. Early initiation of enzyme replacement therapy was pursued. Conclusions: This case emphasizes that children with unexplained musculoskeletal and sensory symptoms should be evaluated for attenuated MPS I, especially when routine studies are inconclusive. Heightened clinical suspicion can reduce diagnostic delay and improve long-term outcomes.

Neurology International doi: 10.3390/neurolint17120206

Authors: Daniele Orsucci

Movement disorders comprise a heterogeneous group of neurological conditions shaped by a complex interplay of genetic and environmental factors [...]

Neurology International doi: 10.3390/neurolint17120204

Authors: Timur Saliev Prim B. Singh

Brain aging is a progressive process marked by cellular dysfunction, chronic inflammation, and increased susceptibility to neurodegenerative diseases. A growing body of evidence identifies cellular senescence, the accumulation of non-dividing, metabolically active cells with a pro-inflammatory secretory profile (SASP), as a key contributor to cognitive decline and brain aging. This review explores the emerging field of senotherapeutics, which includes senolytics (agents that eliminate senescent cells) and senomorphics (agents that suppress SASP without killing cells), as potential strategies to manage brain aging. We summarize recent preclinical studies demonstrating that senotherapeutics can reduce neuro-inflammation, improve synaptic plasticity, and enhance cognitive function in aged animal models. Additionally, we highlight early-phase clinical trials investigating senolytic compounds in Alzheimer’s disease and discuss key challenges, including the delivery of drugs to the brain, biomarker development, and long-term safety. The review concludes that senotherapeutics, particularly when combined with personalized and multimodal approaches, represent a promising avenue for mitigating age-related cognitive decline and promoting healthy brain aging.

Neurology International doi: 10.3390/neurolint17120203

Authors: Marialuisa Zedde Rosario Pascarella

Background: The leptomeninges, comprising the arachnoid and pia mater, serve essential roles in protecting the brain and facilitating cerebrospinal fluid (CSF) circulation. Their significance extends beyond structural support, affecting brain development and function. Methods: This study synthesizes findings from various anatomical, embryological, and neuroimaging research to elucidate the complexities of the leptomeninges. Key methodologies include historical anatomical analysis, contemporary imaging techniques, and examination of pathological states. Results: The review highlights the role of leptomeningeal structures in CSF dynamics, neurovascular interactions, and their involvement in conditions such as hydrocephalus and neurodevelopmental disorders. These insights underscore the leptomeninges’ critical involvement in both normal physiology and disease states. Conclusions: Understanding the intricacies of leptomeningeal anatomy and function is vital for advancing diagnostic and therapeutic approaches in neurodegenerative disorders. This knowledge may facilitate better management strategies in clinical practice, particularly concerning conditions that disrupt CSF flow and brain health.

Neurology International doi: 10.3390/neurolint17120202

Authors: Abdulrazaq Albilali Rema A. Almutawa Elaf A. Almusahel Renad A. Almutawa Nasser A. Almutawa Faisal M. Almutawa Shiekha AlAujan Haya M. AlMalag

Background: Migraine is a highly prevalent neurological disorder and a leading cause of disability, particularly among working-age adults. Although the Work Productivity and Activity Impairment (WPAI) questionnaire is widely used to assess the functional impact of health conditions, no validated Arabic version specific to migraine is currently available. This study was conducted to validate the Arabic version of the WPAI:Migraine questionnaire among Arabic-speaking migraine patients in Saudi Arabia. Methods: A cross-sectional psychometric validation study was conducted at a tertiary headache clinic between June 2023 and January 2024. Adult patients diagnosed with episodic or chronic migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3), completed the Arabic version of the WPAI:Migraine and the validated Arabic version of the Migraine Disability Assessment Scale (MIDAS). Test–retest reliability was assessed after two weeks. Psychometric properties, including reliability, criterion validity, and known-group validity, were evaluated using intraclass correlation coefficients (ICCs), Pearson’s and Spearman’s correlations, and one-way ANOVA. Results: Eighty-two patients completed the study (76.8% female; mean age 38 ± 11 years). The Arabic WPAI:Migraine questionnaire demonstrated substantial-to-almost-perfect test–retest reliability (ICC range: 0.68–0.84). WPAI:Migraine domain scores correlated significantly with MIDAS scores—particularly for activity impairment (r = 0.576), presenteeism (r = 0.526), and absenteeism (r = 0.522)—and increased consistently across MIDAS disability grades, supporting validity. Conclusions: The Arabic WPAI:Migraine questionnaire is a valid and reliable instrument for assessing work productivity and activity impairment among Arabic-speaking migraine patients, suitable for clinical and research use.

Neurology International doi: 10.3390/neurolint17120201

Authors: Lisa B. E. Shields Vasudeva G. Iyer Stephen Furmanek Yi Ping Zhang Christopher B. Shields

Background/Objectives: Atrophy of the thenar muscles (abductor pollicis brevis [APB], opponens pollicis [OP], and flexor pollicis brevis [FPB]) is most commonly caused by carpal tunnel syndrome (CTS). It may also occur following injury to the recurrent motor branch of the median nerve, proximal median nerve neuropathy, medial cord/lower trunk plexopathy, T1 radiculopathy, ventral horn cell disorder at C8 or T1, disuse atrophy, or congenital aplasia. Clinical observation of flattening of the thenar eminence coupled with electrodiagnostic (EDX) and ultrasound (US) studies is valuable in determining the etiology of thenar atrophy. This study describes clinical, EDX, and US findings in a large cohort of patients with thenar muscle atrophy. Methods: This is a review of 197 patients (226 hands) with thenar atrophy who underwent EDX and US studies. Patients were divided into those with total thenar atrophy (all three thenar muscles were atrophic) or partial thenar atrophy (atrophy of one or two thenar muscles) based on clinical and US findings. Results: Of the 226 hands, 174 (77.0%) had partial thenar atrophy, 217 (96.0%) had sensory loss, and all hands demonstrated weakness of the APB and OP muscles on examination. A total of 220 (97.3%) hands had EDX evidence of severe median nerve entrapment at the carpal tunnel. The compound muscle action potentials (CMAPs) of the APB muscle and sensory nerve action potentials (SNAPs) were absent in 186 (82.3%) and 212 (93.8%) hands, respectively. US study showed hyperechoic APB and OP muscles in 225 (99.6%) hands. The Heckmatt grade, determined by US, was 3 in 152 (67.3%) hands, showing increased muscle echogenicity with loss of architecture and reduced bone reflection. Conclusions: In patients with thenar muscle atrophy, EDX studies were not always conclusive for confirming CTS due to an absence of SNAP and CMAP over the APB and second lumbrical muscles. In these cases, US is important to confirm the cause of thenar atrophy.

Neurology International doi: 10.3390/neurolint17120200

Authors: Vinicius Gabriel Coutinho-Costa Isadora Matias Renan Amphilophio Fernandes Michele Siqueira Larissa Araujo Duarte Beatriz Martins Fernandes Jorge Marcondes de Souza Soniza Vieira Alves-Leon Flávia Carvalho Alcantara Gomes

Background: Neuromyelitis optica spectrum disorder (NMOSD) involves demyelinating astrocytopathy. Most cases have autoantibodies against aquaporin-4 (AQP4 ab), but AQP4 ab-negative patients may also meet NMOSD criteria. Overlapping clinical phenotypes of CNS inflammatory demyelinating diseases (IDDs) complicate understanding NMOSD mechanisms. Objectives: Investigate molecules related to neuroinflammation and astrocyte function as potential biomarkers of NMOSD and other IDDs by using clinical data and in vitro assays. Methods: Subjects (176) with different IDDs (NMOSD (37), MS (125), MOGAD (3), ADEM (3) and eight radiologic isolated syndromes (RIS)) were studied. Plasma concentrations of TGF-β and other cytokines were measured by single molecule array (SIMOA), Luminex and ELISA assays. Functional assays used in vitro cultured human astrocytes exposed to NMOSD subjects’ serum, followed by immunolabeling. Results: TGF-β levels were higher in NMOSD patients during attacks compared to inactive phases. AQP4+ groups in inactive phases had lower TGF-β levels than AQP4− groups. No significant difference was found for IL-1β, IL-8, IL-10, IL-17A and Thrombospondin plasma concentrations, with a minor difference for VEGF in the AQP4+ group. Astrocytes exposed to NMOSD AQP4+ and AQP4− subjects serum, with or without TGF-β1, showed no changes in C3, NFkB and HMGB1. However, the content of GLT-1 decreased in AQP4+ serum-treated astrocytes, reversed by TGF-β1. Conclusions: TGF-β may be a potential NMOSD activity biomarker, indicating different disease mechanisms based on AQP4 ab presence.

Neurology International doi: 10.3390/neurolint17120199

Authors: Chih-Hsiang Lin Shiau-Ching Chen Chen-Jui Ho Che-Wei Hsu Shih-Ying Chen Yan-Ting Lu Meng-Han Tsai

Introduction: Autoimmune encephalitis (AE) is a neurological disorder caused by immune responses targeting neuron-surface or synaptic proteins. While its immunological mechanisms have been studied, the genetic underpinnings remain unclear. This study investigates whether rare deleterious variants (RDVs) in immunological genes contribute to AE susceptibility. Method: We enrolled 36 patients with AE and 407 healthy controls without autoimmune diseases. Whole-exome sequencing was performed to identify RDVs, including start-loss, stop-gain, frameshift, splice-site variants, and deleterious missense mutations. We analyzed the distribution of RDVs in an immunological gene set and its subsets. A burden test was used to identify genes significantly associated with AE. Results: Overall, RDVs in the full immunological gene set did not differ between AE patients and controls. However, the T cell receptor signaling pathway subset showed a significantly higher RDV burden in AE patients. Within this pathway, PDK1 was significantly associated with AE. Two additional genes, CAT and MIA, also showed strong associations, although their broader gene subset, cytokines, did not display differential RDV distribution. Discussion: Our findings suggest that RDVs in specific immunological pathways, particularly the T cell receptor signaling pathway, may play a role in AE pathogenesis. The significant associations of PDK1, CAT, and MIA with AE highlight potential genetic contributors to the disease. Further functional studies are necessary to validate these associations and explore their biological relevance, potentially paving the way for improved understanding and future therapeutic targets in AE.

Neurology International doi: 10.3390/neurolint17120198

Authors: Duaa Abdullah Bafail Abrar Abdullah Bafail

Background/Objectives: The optimal timing for initiating oral anticoagulants (OACs) after acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) remains uncertain due to potential risks of recurrent stroke and bleeding. This meta-analysis compares early versus late OAC initiation for recurrent ischemic stroke, major bleeding, intracranial hemorrhage (ICH), systemic embolism, and all-cause mortality. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs), prospective, and retrospective observational studies. Data were pooled using random-effects models, and subgroup analyses were performed to assess outcomes by study design. Heterogeneity was quantified using I2 statistics. Results: A total of 17 studies were included. Early OAC initiation was associated with a significantly lower risk of recurrent ischemic stroke compared to late initiation (OR = 0.74, 95% CI [0.58, 0.95], p = 0.02), with moderate heterogeneity (I2 = 36%, p = 0.08). No significant difference was observed in ICH rates (OR = 0.74, 95% CI [0.41, 1.33], p = 0.32), major bleeding (OR = 1.48, 95% CI [0.51, 4.30], p = 0.47), or systemic embolism (OR = 0.65, 95% CI [0.33, 1.25], p = 0.20). All-cause mortality showed no difference between early and late initiation (OR = 1.00, 95% CI [0.72, 1.39], p = 0.99). Subgroup analyses were consistent with overall findings, and heterogeneity ranged from low to moderate across outcomes. Conclusions: Early initiation of OACs post-AIS in AF patients significantly reduces ischemic stroke recurrence without increasing risks of ICH, major bleeding, systemic embolism, or mortality. These findings support early anticoagulation strategies for selected patients.

Neurology International doi: 10.3390/neurolint17120197

Authors: Jonathan Mingsong Dong Huan Zhong

Background: Neurodegenerative diseases remain a central topic in biomedical research, with Alzheimer’s disease (AD) being the most extensively studied. Recent advances in multi-omics integration, particularly proteomics-based approaches, have enabled a deeper understanding of AD-related molecular pathways and their interconnections. However, challenges such as data heterogeneity and the complexity of large-scale datasets continue to hinder comprehensive integration and model interpretation. Methods: A total of 792 publications were retrieved from PubMed, among which, 27 peer-reviewed studies from 2024 and 2025 focusing on proteomics-anchored multi-omics integration for AD were selected for detailed analysis. These papers were categorized based on their integration strategies, omics combinations, and analytical methodologies. Additionally, statistical analysis of 218 studies published in 2024–2025 was performed to identify dominant omics layers and common integration trends. Results: Proteomics emerged as the most frequently studied omics layer and was most often integrated with transcriptomics in AD multi-omics studies. The analysis also revealed recurrent machine learning methods used for feature extraction and integration, along with key biological pathways implicated in AD pathogenesis, including amyloid metabolism, synaptic function, and neuroinflammation. Conclusions: This review provides a systematic overview of recent trends in proteomics-based multi-omics integration for AD research. It highlights both the scientific advances and methodological limitations in current approaches, serving as a valuable reference for researchers seeking to refine analytical frameworks and design more interpretable, data-driven studies in neurodegenerative disease research.

Neurology International doi: 10.3390/neurolint17120196

Authors: Miriana Caporlingua Jole Castellano Angelo Quartarone Rosella Ciurleo

Background: Alzheimer’s Disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and neurodegeneration. In Italy, AD represents a major public health and socio-economic challenge. This review aims to summarize current Italian research on pharmacological and non-pharmacological interventions, including preclinical studies, clinical trials, rehabilitative approaches, and emerging neuromodulation techniques, highlighting contributions and future directions. Methods: A narrative review of the literature was conducted, focusing on Italian preclinical and clinical studies, observational and real-world evidence, cognitive and physical interventions, music therapy, non-invasive brain stimulation (rTMS, tDCS, tACS), and digital or home-based rehabilitation programs. Results: Italian research has explored different pharmacological strategies, including multitarget compounds, eptastigmine, rotigotine, and combinatorial therapies (donepezil-memantine, citicoline addition). Non-pharmacological interventions, such as cognitive stimulation, motor rehabilitation, music therapy, and multidimensional programs, demonstrated benefits on cognition, behavior, daily functioning, and caregiver well-being. Non-invasive neuromodulation techniques, targeting the dorsolateral prefrontal cortex and precuneus, showed promising effects on memory, attention, and executive functions, especially when combined with cognitive training. Digital health technologies, including telerehabilitation and home-based brain stimulation programs, further enhanced accessibility and adherence. Challenges remain due to fragmented research, small sample sizes, and limited standardization. Conclusions: Italian research on AD reflects a growing emphasis on integrated, multidimensional, and technologically advanced approaches. Strengthening preclinical studies, promoting multicenter collaborations, and combining pharmacological, cognitive, and neuromodulatory strategies may enhance therapeutic efficacy and patient quality of life. Continued investment in innovation and multidisciplinary research positions Italy to contribute meaningfully to global AD management and prevention.

Neurology International doi: 10.3390/neurolint17120195

Authors: Emilio Rubén Pego Pérez María Lourdes Bermello López Eva Gómez Fernández María del Rosario Marín Arnés Mercedes Fernández Vázquez María Irene Núñez Hernández Emilio Gutiérrez García

Background/Objectives: Relapsing-remitting multiple sclerosis (RRMS) is a chronic neurological disease that significantly impacts health-related quality of life (HRQoL). This study aimed to analyze the evolution of HRQoL in individuals with RRMS, identify associated factors, and determine predictive variables. Methods: A prospective observational study was conducted with 35 participants diagnosed with RRMS at the Lucus Augusti University Hospital between January 2023 and March 2025. HRQoL was assessed using the MSQOL-54 questionnaire at baseline, 3 months, and 6 months. Data were analyzed using non-parametric tests to account for the small sample size and non-normal distribution of the variables. Results: Results showed overall stability in HRQoL (mean score: 62.4 ± 14.1 at baseline, 62.8 ± 12.7 at 3 months, and 62.4 ± 11.8 at 6 months), although significant declines were observed in emotional limitations (64.4 ± 23.0 at baseline to 58.9 ± 20.5 at 6 months) and social functioning (70.5 ± 16.7 at baseline to 65.5 ± 12.8 at 6 months). Improvements were noted in pain perception (78.9 ± 23.6 at baseline to 81.8 ± 20.5 at 6 months) and stress (44.3 ± 22.5 at baseline to 48.9 ± 17.8 at 6 months). Factors such as family history (associated with mental health at diagnosis, p = 0.028), autoimmune diseases (associated with physical function at diagnosis, p = 0.035), and lifestyle habits (e.g., tobacco use associated with physical limitations at 3 months, p = 0.045) were significantly associated with HRQoL. Baseline HRQoL emerged as a strong predictor of future scores (Spearman’s correlations, p < 0.01), indicating that early assessments may guide interventions. Conclusions: Although overall HRQoL remains stable in RRMS, specific domains such as emotional and social functioning exhibit progressive decline, highlighting the need for tailored interventions. The findings underscore the importance of integrating early psychosocial support and lifestyle interventions into routine care to mitigate vulnerabilities in emotional and social domains of HRQoL.