Neurology International

15 pages, 1352 KB

Open AccessArticle

Unruptured Intracranial Aneurysm Risk Scores Underperform in Predicting Subsequent Rupture: A Retrospective Single-Center Study

by Kamil Krystkiewicz, Aleksander Kowal, Magdalena Krystkiewicz-Orzechowska, Filip Arczewski, Karol Dziedzic and Marcin Tosik

Neurol. Int. 2025, 17(11), 189; https://doi.org/10.3390/neurolint17110189 - 20 Nov 2025

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Abstract

Background/Objectives: Risk-stratification tools, including the PHASES, UIATS, and ELAPSS, are commonly used to guide management of incidentally detected unruptured intracranial aneurysms (UIAs), but their predictive accuracy in real-world settings remains unclear. This study evaluated how these scores would have advised treatment in patients [...] Read more.

Background/Objectives: Risk-stratification tools, including the PHASES, UIATS, and ELAPSS, are commonly used to guide management of incidentally detected unruptured intracranial aneurysms (UIAs), but their predictive accuracy in real-world settings remains unclear. This study evaluated how these scores would have advised treatment in patients who subsequently presented with aneurysmal subarachnoid hemorrhage (aSAH). Methods: We retrospectively analyzed adults treated for aSAH at Copernicus Memorial Hospital (Łódź, Poland) between January 2022 and June 2024. For each ruptured aneurysm, we calculated PHASES (5-year rupture risk), UIATS recommendation, and ELAPSS (5-year growth risk) as if the lesion had been detected incidentally. Identical assessments were performed for UIAs that remained unruptured. Discrimination for rupture was evaluated using receiver-operating characteristic analysis (AUC). Results: Of 180 aneurysms (mean age 66.9 ± 11.3 years), 103 (57%) were ruptured. Patients with ruptured aneurysms were significantly older (69.9 vs. 64.0 years; p = 0.003), while sex, hypertension, smoking, and aneurysm morphology did not differ significantly. UIATS more frequently favored conservative management in ruptured aneurysms (56.3% vs. 39.0%; p = 0.046). PHASES (1.6% vs. 1.6%) and ELAPSS (3-year: 14.5% vs. 12.6%; 5-year: 22.6% vs. 20.0%) showed no significant differences between groups. Age was the only independent predictor of rupture (OR = 1.05/year; p < 0.001). The model’s cross-validated AUC was 0.731. Conclusions: Most ruptured aneurysms would not have been recommended for treatment based on UIATS. PHASES, ELAPSS, and UIATS did not reliably discriminate between ruptured and unruptured aneurysms, emphasizing the need for more precise and individualized risk assessment tools. Full article

(This article belongs to the Special Issue Cerebrovascular Disease: Update on Diagnosis and Treatment)

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25 pages, 1877 KB

Open AccessSystematic Review

Neuromodulatory Effects of Transcranial Pulse Stimulation (TPS) in Neurological and Psychiatric Disorders—A Systematic Review and Meta-Analysis

by Selma Polte, Larissa Klingmann, Anna Seßmann, Svenja Schwichtenberg, Christoph S. Herrmann, Karsten Witt and Mandy Roheger

Neurol. Int. 2025, 17(11), 188; https://doi.org/10.3390/neurolint17110188 - 18 Nov 2025

Viewed by 646

Abstract

Background: Transcranial pulse stimulation (TPS) is an innovative non-invasive brain stimulation technique using ultrasonic waves. Despite its application in first clinical trials, so far, no systematic overview of its effects across different patient populations has been conducted. Objectives: This systematic review and meta-analysis [...] Read more.

Background: Transcranial pulse stimulation (TPS) is an innovative non-invasive brain stimulation technique using ultrasonic waves. Despite its application in first clinical trials, so far, no systematic overview of its effects across different patient populations has been conducted. Objectives: This systematic review and meta-analysis examines the effects of TPS on cognitive, motor, and mental health outcomes as well as on patient safety in neurological and psychiatric disorders. Methods: We conducted a literature search in MEDLINE, PsycINFO & PsycArticles, CENTRAL, Web of Science, and Google Scholar, covering the period from January 2013 to December 2024. Two independent reviewers conducted the study selection, data extraction, and quality assessment. To evaluate the risk of bias, the RoB2 tool was used for randomized studies and the ROBINS-I tool for non-randomized studies. Results: A total of fifteen studies (five randomized controlled trials and ten non-blinded, single-arm trials) including both adolescent and adult and elderly patient populations (Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder) were included. Positive effects of TPS intervention on cognitive, motor, and mental health outcomes, as well as a high safety profile, were demonstrated in a majority of the studies and outcome parameters. However, limitations of the included studies persist due to small sample sizes, lack of control groups, retrospective analyses, and heterogeneity of study protocols and measurements. Conclusions: TPS is a safe and promising method for treating neurological and psychiatric disorders. To better assess the potential of this innovative technique, standardized protocol procedures and larger, sham-controlled trials are needed. Full article

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9 pages, 5779 KB

Open AccessCase Report

Extracranial Vertebral Artery Dissecting Aneurysm Presenting as Vertebrobasilar Stroke in a Young Adult: Case Report of Flow-Diverter Stenting

by Maria Angelica-Coronel, Melissa Luque-Llano, Narledis Nuñez-Bravo, Carlos Rebolledo and Ernesto Barceló-Martínez

Neurol. Int. 2025, 17(11), 187; https://doi.org/10.3390/neurolint17110187 - 18 Nov 2025

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Abstract

Background: Extracranial vertebral artery aneurysms (EVAAs) are exceptionally rare vascular lesions and an uncommon cause of posterior circulation stroke. Their diagnosis is often delayed due to nonspecific symptoms, yet prompt recognition is essential to guide management. Objective: This study aimed to [...] Read more.

Background: Extracranial vertebral artery aneurysms (EVAAs) are exceptionally rare vascular lesions and an uncommon cause of posterior circulation stroke. Their diagnosis is often delayed due to nonspecific symptoms, yet prompt recognition is essential to guide management. Objective: This study aimed to report a rare case of an extracranial vertebral artery dissecting aneurysm presenting as a posterior circulation stroke in a young adult, successfully managed with flow-diverter stenting. Clinical Case: A 33-year-old woman presented with sudden-onset dysarthria, vertigo, nausea, and vomiting. Brain magnetic resonance imaging revealed infarcts in the left occipital lobe, cerebellar peduncle, and both cerebellar hemispheres. Computed tomography angiography (CTA) demonstrated a fusiform aneurysm in the V2 segment of the left vertebral artery, and digital subtraction angiography (DSA) confirmed a dissecting aneurysm. The patient was successfully treated with a flow-diverting stent and remained stable at 6 months’ follow-up with mRS 1. Results: EVAA are uncommon but can manifest as posterior circulation ischemic events in young patients. Endovascular treatment with flow-diverting stents has been reported as a feasible option in selected cases, although evidence remains limited to case reports and small series. Conclusions: This case underscores the importance of considering rare yet potentially treatable etiologies of vertebrobasilar stroke in young patients and highlights the value of a multidisciplinary approach to management. Full article

(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)

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20 pages, 450 KB

Open AccessSystematic Review

Speed Matters: Challenging the Notion of Velocity-Independent Rigidity Using Technological Devices in People with Parkinson’s Disease: A Systematic Review

by Roberto Cano-de-la-Cuerda, Cecilia Estrada-Barranco, Patricia Martín-Casas, Selena Marcos-Antón, Rosa María Ortiz-Gutiérrez, Sofía Laguarta-Val and Carmen Jiménez-Antona

Neurol. Int. 2025, 17(11), 186; https://doi.org/10.3390/neurolint17110186 - 17 Nov 2025

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Abstract

Objectives: The application of well-controlled, quantitative measurement systems has challenged the traditional notion that rigidity in Parkinson’s disease (PD) is a velocity-independent phenomenon. This review aimed to evaluate whether rigidity in PD is velocity-dependent or velocity-independent across different joints, body regions, testing [...] Read more.

Objectives: The application of well-controlled, quantitative measurement systems has challenged the traditional notion that rigidity in Parkinson’s disease (PD) is a velocity-independent phenomenon. This review aimed to evaluate whether rigidity in PD is velocity-dependent or velocity-independent across different joints, body regions, testing speeds, and methodologies. Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of cross-sectional studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), and reporting completeness was evaluated with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: Seventeen studies were included and analyzed by the body part assessed (wrist, elbow, hand, knee, trunk). Rigidity quantification in PD used various biomechanical technologies, sometimes combined with neurophysiological methods. Although rigidity is classically considered velocity-independent, experimental evidence suggests a more complex behavior, partially velocity-dependent, especially at moderate to high angular velocities. Methodological quality was variable but generally acceptable, with more recent studies showing stronger adherence to AXIS. However, compliance with STROBE reporting standards remained inconsistent. Conclusions: While rigidity in PD has not been classically defined as velocity-dependent, current evidence indicates that, under specific testing conditions, rigidity increases with passive movement velocity. These findings challenge traditional clinical assumptions and emphasize the need for standardized measurement protocols. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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13 pages, 1597 KB

Open AccessArticle

Gut Microbiota Affects Mouse Social Behavior via Hippuric Acid Metabolism

by Momona Tsukui, Sosuke Yagishita, Shinji Tokunaga, Shuji Wakatsuki and Toshiyuki Araki

Neurol. Int. 2025, 17(11), 185; https://doi.org/10.3390/neurolint17110185 - 11 Nov 2025

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Abstract

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically characterized by impaired social communication. Previous reports have postulated gut microbiota to be an important non-genetic factor affecting ASD-like phenotypes in mice, as germ-free (GF) mice show impaired social communication. Results: In this [...] Read more.

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically characterized by impaired social communication. Previous reports have postulated gut microbiota to be an important non-genetic factor affecting ASD-like phenotypes in mice, as germ-free (GF) mice show impaired social communication. Results: In this study, we identified hippuric acid (HA) as a metabolite generated via a gut microbiome-dependent mechanism that plays a role in the acquisition of social behavior during mouse development. We discovered that oral or intraperitoneal HA administration to GF mice normalizes their social behavior. Furthermore, HA administration restored oxytocin expression in the hypothalamic paraventricular nucleus and secretin expression in the subfornical organ, suggesting that HA may activate the secretin–oxytocin system to influence the social behavior of mice. Conclusions: These findings indicate that HA may serve as an important gut microbiome-dependent mediator affecting the brain mechanisms involved in regulating social behavior. Full article

(This article belongs to the Collection Exclusive Papers from the Editorial Board Members (EBMs) of Neurology International)

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12 pages, 531 KB

Open AccessArticle

by Sofia Bezerra, Ricardo Soares dos Reis, Maria José Sá and Joana Guimarães

Neurol. Int. 2025, 17(11), 184; https://doi.org/10.3390/neurolint17110184 - 11 Nov 2025

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Abstract

Background/Objectives: Optic neuropathies (ON) are a clinically heterogeneous group of disorders that can cause profound and lasting visual disability, with wide-ranging effects on patients’ quality of life. Although the NEI-VFQ-25 is an instrument for assessing vision-related quality of life (VRQoL), few studies [...] Read more.

Background/Objectives: Optic neuropathies (ON) are a clinically heterogeneous group of disorders that can cause profound and lasting visual disability, with wide-ranging effects on patients’ quality of life. Although the NEI-VFQ-25 is an instrument for assessing vision-related quality of life (VRQoL), few studies have systematically compared patient-reported outcomes across multiple ON subtypes, especially in underrepresented populations. We aimed to delineate how etiological differences and longitudinal visual acuity trajectories shape VRQoL in a diverse Portuguese cohort with ON. Methods: This retrospective, cross-sectional study included 152 patients diagnosed with ON and followed at São João University Hospital, Portugal. All participants completed the validated NEI-VFQ-25. Diagnosis-specific differences in VRQoL were interrogated using ANCOVA and linear mixed-effects models, controlling for age and sex. Visual acuity changes over time were analyzed in relation to patient-reported outcomes. Results: Substantial heterogeneity in VRQoL was observed across ON subtypes. Patients with MS-related ON (MS-RON) and idiopathic ON reported significantly higher NEI-VFQ-25 scores in domains such as general vision, mental health, and dependency (F = 3.30, p = 0.013; ηp² = 0.08), while those with ischemic or other inflammatory etiologies showed persistently lower scores. Notably, both final visual acuity and diagnosis were independently associated with NEI-VFQ-25 composite scores, highlighting the correlation between objective and subjective measures of visual function. Age and diagnosis independently predicted poorer VRQoL. Conclusions: This study provides the first comprehensive evaluation of vision-related quality of life (VRQoL) across a diverse cohort of optic neuropathy patients in a Portuguese tertiary center, using the NEI-VFQ-25. Our results underscore the heterogeneity of functional impact across ON subtypes, emphasizing the value of integrating sensitive, multidimensional assessment tools into neuro-ophthalmic clinical care, especially in populations historically underrepresented in research. Full article

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17 pages, 4256 KB

Open AccessSystematic Review

Safety and Efficacy of Rivaroxaban Versus Warfarin in Cerebral Venous Thrombosis: A Comprehensive Meta-Analysis

by Redoy Ranjan and Gie Ken-Dror

Neurol. Int. 2025, 17(11), 183; https://doi.org/10.3390/neurolint17110183 - 8 Nov 2025

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Abstract

Background: Long-term management of cerebral venous thrombosis (CVT) with rivaroxaban is still under evaluation. The primary objective was to compare the contemporary evidence of the safety and efficacy of rivaroxaban versus warfarin in the long-term (≥ 6 months) treatment of CVT. Methods: We [...] Read more.

Background: Long-term management of cerebral venous thrombosis (CVT) with rivaroxaban is still under evaluation. The primary objective was to compare the contemporary evidence of the safety and efficacy of rivaroxaban versus warfarin in the long-term (≥ 6 months) treatment of CVT. Methods: We searched electronic databases up to 30 April 2025 for randomised control trials (RCTs) and observational studies in CVT management. We utilised the Mantel–Haenszel (M-H) method with a fixed-effects model to calculate risk differences (RDs) between rivaroxaban and warfarin arms. The ROB 2.0 and ROBINS-I tools were used to observe the risk of bias among included studies. Results: A total of 12 studies were identified (4 RCTs and 8 observational cohorts), evaluating 1174 patients treated with rivaroxaban (n = 262) or warfarin (n = 912). The rate of recurrence of venous thrombosis was 4% lower among rivaroxaban- compared to warfarin-treated patients (1.5% vs. 4.0%; RD = −0.04; p = 0.04). However, non-recanalisation events were identical among rivaroxaban and warfarin arms (16.4% vs. 16.5%; RD = −0.01, p = 0.68). Additionally, long-term all-cause mortality (p = 0.39), clinically relevant bleeding events (p = 0.18), new intracranial haemorrhage (p = 0.79), and good clinical outcome (p = 0.92) events were similar between rivaroxaban and warfarin arms. While RCTs and observational cohorts have methodological concerns and potential bias, we validated our results by excluding studies with serious or critical risks of bias to ensure the robustness of our findings. Conclusions: Compared to warfarin, rivaroxaban offers lower recurrence rates with similar efficacy and safety profiles along with improved clinical convenience. Full article

(This article belongs to the Section Brain Tumor and Brain Injury)

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22 pages, 2399 KB

Open AccessArticle

Interaction Between DRD2 rs1076560 Genotype and Stimulant Dependence on Impulsivity and Self-Reported ADHD Traits in Men

by Milena Lachowicz, Remigiusz Recław, Jolanta Chmielowiec, Krzysztof Chmielowiec, Kinga Łosińska, Dariusz Larysz and Anna Grzywacz

Neurol. Int. 2025, 17(11), 182; https://doi.org/10.3390/neurolint17110182 - 5 Nov 2025

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Abstract

Background and Objectives: The dopamine D2 receptor (DRD2) plays a central role in fronto-striatal circuits regulating cognitive control and reward processing. The rs1076560 polymorphism alters receptor isoform expression, potentially modifying impulsivity and vulnerability to stimulant use disorders. We examined gene–environment interactions [...] Read more.

Background and Objectives: The dopamine D2 receptor (DRD2) plays a central role in fronto-striatal circuits regulating cognitive control and reward processing. The rs1076560 polymorphism alters receptor isoform expression, potentially modifying impulsivity and vulnerability to stimulant use disorders. We examined gene–environment interactions between rs1076560 and stimulant dependence in relation to impulsivity, ADHD traits, and hedonic capacity. Methods: A total of 517 men (235 stimulant-dependent, 282 controls) completed the Barratt Impulsiveness Scale (BIS-11), Adult ADHD Self-Report Scale (ASRS v1.1), and Snaith–Hamilton Pleasure Scale (SHAPS). Genotyping for rs1076560 was performed using real-time PCR, and two-way ANOVAs tested genotype-by-group effects. Results: Significant genotype-by-group interactions were observed across all BIS-11 subscales and ASRS scores. In the stimulant-dependent group, C/C homozygotes showed the highest levels of attentional impulsivity and attentional dysregulation compared to both A/C and C/C controls. In contrast, within the control group, A/A homozygotes demonstrated higher motor impulsivity, non-planning impulsivity, and BIS-11 total scores than C/C controls. No significant main effects or interactions were found for SHAPS scores. Conclusions: DRD2 rs1076560 moderates impulsivity-related traits through dopaminergic pathways relevant to executive dysfunction in stimulant use disorders. These findings highlight a neurobiological mechanism of addiction vulnerability and may inform precision approaches in neurology and psychiatry. Full article

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20 pages, 664 KB

Open AccessSystematic Review

Design of Trials for Cerebral Small Vessel Disease and Vascular Cognitive Impairment

by Elizabeth Phan, Shi Pei Loo and Terence J. Quinn

Neurol. Int. 2025, 17(11), 181; https://doi.org/10.3390/neurolint17110181 - 4 Nov 2025

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Abstract

Background/Objectives: Cerebral small vessel disease (cSVD) and vascular cognitive impairment (VCI) are major contributors to stroke and dementia. Despite their importance, there are few effective treatments for cSVD and VCI. Variability in cSVD/VCI populations, intervention targets, and outcome selection may contribute to inconsistencies [...] Read more.

Background/Objectives: Cerebral small vessel disease (cSVD) and vascular cognitive impairment (VCI) are major contributors to stroke and dementia. Despite their importance, there are few effective treatments for cSVD and VCI. Variability in cSVD/VCI populations, intervention targets, and outcome selection may contribute to inconsistencies and challenges in clinical trial design. We reviewed the design of cSVD and VCI clinical trials to describe current practice in the selection of populations, interventions, and outcomes. Methods: We systematically searched Ovid Medline, Embase, and PsychInfo databases for recently completed cSVD/VCI trials and searched online trial registries (ClinicalTrials.gov, European Union Clinical Trials Register, and International Clinical Trials Registry Platform) for ongoing cSVD/VCI trials. We determined the use of specific categories of inclusion and exclusion criteria, interventions, and outcomes in the included trials and described these as counts and percentages. Results: We included a total of 82 cSVD trials and 120 VCI trials. Neuroimaging features were most frequently used as inclusion criteria for cSVD (88%) and cognition for VCI (88%). There was substantial variation in eligible ages for participation. Both cSVD and VCI trials largely excluded patients with comorbidities, vascular risk factors, and neuropsychiatric disorders, with a notable proportion of cSVD trials excluding on the basis of functional impairment. The most studied intervention classes were repurposed cardiovascular drugs (40%) for cSVD and Traditional Chinese Medicine (35%) in VCI. The most common primary outcome category was neuroimaging for cSVD (53%) and cognition for VCI (86%). Notably, functional outcomes were underused in both cSVD and VCI trials (13% and 12%, respectively, for primary outcomes). Conclusions: We have identified substantial variability in all aspects of cSVD and VCI clinical trial design. Inconsistent neuroimaging criteria and exclusions based on common long-term conditions limit the generalisability of findings. There is a need for greater focus on clinical outcomes, particularly functional ability, to better reflect treatment impact. Increased integration and standardisation of cSVD and VCI trial design is needed to accelerate progress in developing treatments. Full article

(This article belongs to the Special Issue Cognitive Impairment After Stroke)

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22 pages, 1586 KB

Open AccessArticle

The Cognitive Changes Among Patients over 65 Years of Age in a Rural Area—The Preliminary Report of Protective and Predisposing Factors

by Radoslaw Zachara, Daria Gendosz de Carrillo, Adam Wlaszczuk, Agnieszka Gorzkowska, Wiktoria Mazur and Halina Jedrzejowska-Szypulka

Neurol. Int. 2025, 17(11), 180; https://doi.org/10.3390/neurolint17110180 - 3 Nov 2025

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Abstract

Background: Aβ1-42 and APOE concentrations, as well as Aβ42/40 ratio, may be considered as a link between hypertension (HTN) or diabetes mellitus (DM), brain amyloidosis, and dementia. HTN and DM are associated with cognitive impairment and may contribute to the development of Alzheimer’s [...] Read more.

Background: Aβ1-42 and APOE concentrations, as well as Aβ42/40 ratio, may be considered as a link between hypertension (HTN) or diabetes mellitus (DM), brain amyloidosis, and dementia. HTN and DM are associated with cognitive impairment and may contribute to the development of Alzheimer’s disease (AD). This preliminary study aimed to evaluate the impact of vascular risk factors on the concentration of biochemical AD markers and cognitive state. As it is a cross-sectional study in nature, causal relationships cannot be established. Methods: The study was conducted in the south of Poland among a rural population over 65 years of age. A total of 58 patients qualified into the study were divided into groups according to the presence of HTN (n = 18) or HTN coexisting with DM (n = 40). A healthy control group was also formed (n = 20), resulting in 78 study participants. The study population was also divided based on M-ACE results, forming a normal cognition group (NC) and a deteriorated cognition group (DC). Biochemical tests, neurological scales assessments, and ultrasound examinations were conducted. Results: Patients who scored in the normal range on the M-ACE had higher Aβ1-42 (median 38.52 vs. 27.35 pg/mL, p = 0.02) and apoE concentrations (median 125.0 vs. 65.73 μg/mL, p = 0.002), and a higher Aβ42/40 ratio (median 0.39 vs. 0.29 p < 0.000) compared to the DC group. Considering the study groups, the highest Aβ42/40 ratio was found among the HC group (median 0.47). The median score for the M-ACE scale was 3 points lower when HTN and DM coexisted, compared to the sole diagnosis of HTN (25 points and 28 points, respectively). A higher number of years of education correlated with better M-ACE results. Lipid and uric acid concentrations were not related to M-ACE or MMSE scores. An inverse relationship connected Aβ1-40 and Aβ1-42 to BMI, the duration of HTN treatment, and glycated hemoglobin. Conclusions: Aβ1-42, APOE, and Aβ42/40 are not only correlated with cognition but also related to patient’s disease profile. The coexistence of DM and HTN was associated with the most significant decline in cognitive functioning. However, a higher number of years of education may protect against the development of dementia in old age. The roles of cholesterol and uric acid in cognitive decline are still inconclusive. Full article

(This article belongs to the Section Aging Neuroscience)

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10 pages, 3602 KB

Open AccessCase Report

Oculomotor Abnormalities in Anti-Glutamic Acid Decarboxylase-Positive Stiff Person Syndrome

by Pavol Skacik, Jaroslav Petrisin, Kristian Sveda, Monika Turcanova-Koprusakova, Milan Grofik, Stefan Sivak and Egon Kurca

Neurol. Int. 2025, 17(11), 179; https://doi.org/10.3390/neurolint17110179 - 3 Nov 2025

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Abstract

Background: Antibodies to glutamic acid decarboxylase (anti-GAD) can give rise to stiff person syndrome (SPS), an infrequent autoimmune condition of the central nervous system marked by fluctuating muscular rigidity and stimulus-evoked spasms. Disturbances in eye-movement control are rarely identified yet may provide insight [...] Read more.

Background: Antibodies to glutamic acid decarboxylase (anti-GAD) can give rise to stiff person syndrome (SPS), an infrequent autoimmune condition of the central nervous system marked by fluctuating muscular rigidity and stimulus-evoked spasms. Disturbances in eye-movement control are rarely identified yet may provide insight into underlying neural involvement. Methods: Two individuals with anti-GAD-related SPS showing distinctive ocular-motor abnormalities were examined with quantitative videonystagmography, supplemented by representative video documentation. Results: Recordings demonstrated varied patterns of ocular-motor disturbance, including reduced smooth-pursuit accuracy, delayed saccadic initiation, dysmetria, intrusive saccades, and several nystagmus types. Partial improvement occurred after immunomodulatory therapy. Conclusions: These findings extend current understanding of the anti-GAD SPS phenotype and indicate that quantitative analysis of eye movements may offer a sensitive, non-invasive marker of disease activity. Larger, prospective studies are needed to clarify prevalence and responsiveness to treatment. Full article

(This article belongs to the Special Issue Biomarker Research in Neuromuscular Diseases)

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9 pages, 2714 KB

Open AccessCase Report

Rare Pediatric Posterior Stroke Case Report with Discussion of Brainstem Lesions

by Lauren A. Gould, Matthew Carman, Gian Rossi and Jasvinder Dhillon

Neurol. Int. 2025, 17(11), 178; https://doi.org/10.3390/neurolint17110178 - 3 Nov 2025

Viewed by 453

Abstract

Introduction: The rates of pediatric ischemic stroke incidence have more than doubled over the past 3–4 decades; however, pediatric posterior circulation strokes are even more uncommon. These rising incidence rates have led to increasing awareness of pediatric strokes and the development of institutional [...] Read more.

Introduction: The rates of pediatric ischemic stroke incidence have more than doubled over the past 3–4 decades; however, pediatric posterior circulation strokes are even more uncommon. These rising incidence rates have led to increasing awareness of pediatric strokes and the development of institutional guidelines regarding these patients to optimize outcomes when possible. Case Report: We describe a rare case of acute ischemic posterior circulation stroke in a 14-year-old previously healthy adolescent boy who presented with right-sided facial droop, dysarthria, and right-sided hemiplegia. An MRI of the brain demonstrated an acute infarct in the brainstem, and an echocardiogram demonstrated a patent foramen ovale (PFO). We also discuss how to localize brainstem lesions to a specific location within the brainstem and associated blood supply using symptomatology. Conclusions: All stroke patients require evaluation for possible etiologies of stroke and possible underlying risk factors. Nearly half of patients who suffer from cryptogenic stroke are found to have a PFO, and adult studies have shown that PFO closure is associated with reduced recurrent cryptogenic strokes, although pediatric-specific data is lacking. If a posterior stroke is suspected, specifically in the brainstem, then the Brainstem Rules of Four may be utilized to localize these lesions and identify blood supply using simplified knowledge of the brainstem anatomy. Full article

(This article belongs to the Section Brain Tumor and Brain Injury)

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12 pages, 816 KB

Open AccessArticle

Blood–Brain Barrier Dysfunction, Edema Formation and Functional Recovery in Ischemic and Hemorrhagic Stroke: A Retrospective Study

by Christian A. Müller, Jochen A. Sembill, Bernd Kallmünzer, Maximilian Bailer, Ludwig Singer, Tobias Engelhorn, Arnd Dörfler, Stefan Schwab, Stefanie Balk and Maximilian I. Sprügel

Neurol. Int. 2025, 17(11), 177; https://doi.org/10.3390/neurolint17110177 - 1 Nov 2025

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Abstract

Objectives: We aimed to determine temporal patterns of blood–brain barrier (BBB) dysfunction, edema formation and functional recovery in acute stroke. Materials and Methods: Patients of two observational studies on ischemic and hemorrhagic stroke between 2006 and 2019 were analyzed. Blood–brain barrier dysfunction was [...] Read more.

Objectives: We aimed to determine temporal patterns of blood–brain barrier (BBB) dysfunction, edema formation and functional recovery in acute stroke. Materials and Methods: Patients of two observational studies on ischemic and hemorrhagic stroke between 2006 and 2019 were analyzed. Blood–brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio. Edema formation was measured on all available imaging scans during hospital stay. Relative edema was defined as the ratio of edema volume to stroke volume. Multivariable regression models were applied to analyze associations and calculate predicted probabilities. Results: Overall, 138 stroke patients, 103 (74.6%) with ischemic stroke and 35 (25.4%) with hemorrhagic stroke, were analyzed. The predicted probability of substantial BBB dysfunction was approximately 46 (37–55) % among patients analyzed on 1 day after symptom onset and declined with increasing time, thereafter reaching 10 (3–29) % on day 30. The maximal extent of edema was lower in ischemic versus hemorrhagic stroke (relative edema: 1.5 [1.2–1.8] vs. 2.6 [1.9–4.5], p = 0.003) and occurred earlier after stroke onset (5.9 [4.6–8.5] days vs. 12.3 [9.7–16.4] days, p = 0.009). BBB dysfunction was associated with increased edema formation (adjusted relative edema: 4.0 [2.8–4.5] vs. 2.3 [1.8–3.0], p = 0.037) and lower chances of functional recovery (20/48 [41.7%] vs. 51/90 [56.7%], adjusted Odds Ratio: 0.37 [0.16–0.88], p = 0.025) in both ischemic and hemorrhagic stroke patients. Conclusions: BBB dysfunction frequently occurred in acute ischemic and hemorrhagic stroke and was associated with secondary injury and worse clinical outcomes. Future studies should evaluate BBB dysfunction as a potential therapeutic target using advanced imaging techniques early after stroke onset. Edema formation was aggravated and prolonged in hemorrhagic versus ischemic stroke. Full article

(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)

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34 pages, 7149 KB

Open AccessArticle

Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD Study): A Comprehensive Meta-Analysis

by Muskaan Gupta, Kevin J. Spring, Roy G. Beran and Sonu Bhaskar

Neurol. Int. 2025, 17(11), 176; https://doi.org/10.3390/neurolint17110176 - 1 Nov 2025

Viewed by 1082

Abstract

Background: Ischemic stroke (IS) remains a leading global cause of mortality, recurrence, and long-term disability, with survivors also at risk of post-stroke dementia (PSD) and cognitive impairment (PSCI). The precise impact of statin therapy across different IS populations, including those with cardioembolic/atrial fibrillation [...] Read more.

Background: Ischemic stroke (IS) remains a leading global cause of mortality, recurrence, and long-term disability, with survivors also at risk of post-stroke dementia (PSD) and cognitive impairment (PSCI). The precise impact of statin therapy across different IS populations, including those with cardioembolic/atrial fibrillation (CE/AF) strokes and patients with low-baseline low-density lipoprotein (LDL) cholesterol, remains unclear, as does the influence of statin timing, intensity, type, and solubility. Methods: We conducted the Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD) meta-analysis, synthesizing evidence from 51 studies (n = 521,126), to evaluate the association between post-stroke statin therapy and key outcomes: all-cause mortality, stroke recurrence, cognition, and C-reactive protein (CRP). PSD was defined as new, persistent cognitive decline meeting standard diagnostic criteria, and PSCI as measurable but sub-threshold cognitive deficits. Random-effects models were used, and certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: Statin therapy significantly reduced all-cause mortality within 3 months (OR 0.32), at 1 year (OR 0.35), and beyond 1 year (OR 0.56). Stroke recurrence was modestly reduced both within 1 year (OR 0.77) and after 1 year (OR 0.76). Statin use was associated with a lower risk of PSD (OR 0.74) but not PSCI overall. Benefits extended to CE/AF-related strokes and patients with low-baseline LDL cholesterol, both showing significantly lower mortality with statin use. Early initiation (<24 h) was linked with reduced recurrence, though effects of statin intensity, type, and solubility were inconsistent. Statins also significantly reduced CRP levels, underscoring anti-inflammatory and pleiotropic mechanisms. Conclusions: The ISMARDD study demonstrates that statins confer survival benefit and selective cognitive protection (notably reduced PSD risk) after ischemic stroke, with modest recurrence benefit, supporting their broad use in secondary prevention. These findings highlight the need for precision-guided approaches tailored to stroke subtype, pharmacogenomics, and treatment timing to optimize therapeutic outcomes. Full article

(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)

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17 pages, 706 KB

Open AccessReview

Impact of Stroke Code Activation on Functional Outcomes and the Role of Nursing in Neurorehabilitation: A Systematic Review

by Álvaro Astasio-Picado, Jesus Jurado-Palomo and Clara Fátima Rodriguez-Urbaneja

Neurol. Int. 2025, 17(11), 175; https://doi.org/10.3390/neurolint17110175 - 29 Oct 2025

Viewed by 1184

Abstract

Introduction: Stroke is one of the leading causes of death and disability worldwide. In this context, early activation of the Stroke Code and a structured neurorehabilitation approach are key determinants of patients’ functional outcomes. Objectives: We aimed to evaluate the impact of Stroke [...] Read more.

Introduction: Stroke is one of the leading causes of death and disability worldwide. In this context, early activation of the Stroke Code and a structured neurorehabilitation approach are key determinants of patients’ functional outcomes. Objectives: We aimed to evaluate the impact of Stroke Code activation on the functional prognosis of patients who have suffered an ischemic stroke, analyzing the time-dependent relationship and the effectiveness of reperfusion therapies. Additionally, we sought to examine the role of nursing in inpatient neurorehabilitation. Methods: A systematic review was conducted following the PRISMA 2020 guidelines. Scientific studies published between 2020 and 2025 were reviewed across five databases: PubMed; Cochrane Library; Dialnet; Web of Science; and Scopus. Eligibility criteria were applied, and validated tools were used to assess methodological quality and risk of bias. Results: Thirteen studies were included, involving a total sample of 80,555 patients. Age; lesion volume; and time to treatment were found to be key prognostic factors. Early implementation of reperfusion therapies (thrombolysis and/or thrombectomy), combined with nursing-led neurorehabilitation interventions, significantly improved neurological status, functional independence, and quality of life. Conclusions: Stroke Code activation has a significant positive influence on functional prognosis. Reducing treatment delays and optimizing reperfusion therapies are critical. Furthermore, the role of nursing in hospital-based neurorehabilitation is essential to support patient recovery and functionality. Full article

(This article belongs to the Special Issue Advances in Novel Treatment and Rehabilitation for Strokes)

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15 pages, 724 KB

Open AccessArticle

Multidimensional Impairment in Multiple Sclerosis: Physical Disability, Cognitive Dysfunction, Sleep Disturbance, Fatigue, Depression, and Their Impact on Quality of Life—A Possible Common Pathological Pathway

by Simona Petrescu, Maria-Melania Dumitru-Martoiu and Cristina Aura Panea

Neurol. Int. 2025, 17(11), 174; https://doi.org/10.3390/neurolint17110174 - 22 Oct 2025

Viewed by 563

Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which can lead to physical and cognitive disability, fatigue, depression, and sleep disturbance, all of which may impair quality of life (QoL). While the physical disability is widely known [...] Read more.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which can lead to physical and cognitive disability, fatigue, depression, and sleep disturbance, all of which may impair quality of life (QoL). While the physical disability is widely known to influence the QoL, the relative contributions of cognitive impairment, fatigue, and sleep quality remain incompletely defined. Objectives: To evaluate the relationship between QoL, physical and cognitive disability, sleep quality, fatigue, and depression in people with MS (PwMS), and to explore phenotype-specific differences between relapsing and progressive forms. Methods: In this monocentric cross-sectional study, 112 PwMS underwent physical assessment (EDSS, MSFC), cognitive testing (SDMT, PASAT, MoCA, MMSE), and QoL evaluation (MSIS-29, EQ-5D, EQ-VAS, MSNQ). A subgroup of 29 patients also completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI). Correlation and group analyses were performed. Results: Progressive MS patients showed greater physical disability (mean EDSS 5.8 vs. 2.6, p < 0.001), poorer cognitive performance, and lower QoL. Across the cohort, QoL strongly correlated with physical disability (EDSS) and cognitive performance (SDMT), with physical measures showing stronger associations. In relapsing MS, physical and cognitive impairment were linked to reduced QoL, whereas in progressive MS, physical disability predominated. In the sleep subgroup, poorer PSQI scores, longer sleep latency, and daytime sleepiness correlated with higher fatigue (MFIS), depressive symptoms (BDI), and reduced QoL (MSIS-29, EQ-5D). Conclusions: QoL in MS reflects the combined burden of physical disability, cognitive impairment, fatigue, depression, and poor sleep quality, with phenotype-specific patterns. While physical disability is the main QoL determinant in progressive MS, cognitive deficits with slowed processing speed play an important role in relapsing MS. Comprehensive, multidimensional assessment, including sleep and mood screening, may support individualized management strategies in MS. Full article

(This article belongs to the Topic Management of Multiple Sclerosis: Past, Present and Promise)

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Neurol. Int., Volume 17, Issue 11 (November 2025) – 16 articles

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