Neurology International

11 pages, 741 KiB

Open AccessArticle

Effect of Cilostazol in the Expression of Biomarkers and Neurological Outcome Following Experimentally Induced Cerebrovascular Accident—Experimental Protocol

by Christiana Anastasiadou, Stavroula Kastora, Alkistis Kapelouzou, Anastasios Papapetrou, Angelos Megalopoulos, Nikolaos Kostomitsopoulos, Efthymios Paronis, Andreas Lazaris, George Geroulakos, Christos Liapis, Nikolaos Saratzis and John Kakisis

Neurol. Int. 2025, 17(8), 126; https://doi.org/10.3390/neurolint17080126 - 11 Aug 2025

Abstract

Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and [...] Read more.

Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and combinatorial pre-treatment upon neurological status and biomarkers, namely protein S100b, GFAP, procalcitonin, and galectin-3, following stroke. Methods: Twelve-week-old Sprague–Dawley rats were randomly assigned to four groups, each containing six rats: control group (normal saline), cilostazol group (30 mg/kg/daily), aspirin group (10 mg/kg/daily), and aspirin/cilostazol group. Each substance was administered by gavage for four weeks. All animals were subjected to cerebral ischemia for 2 h using intraluminal middle cerebral artery occlusion. A neurological examination was performed, serum concentrations of biomarkers were determined, and the animals were then sacrificed. Results: All treatment groups exhibited variations in the severity of immediate neurological presentation. Unlike the control group, where all rats presented with severe focal neurology or mortality, most rats in the treatment groups displayed no to moderate focal neurology. Moreover, the aspirin/cilostazol group consistently exhibited significantly lower levels in the studied biomarkers compared to other groups. Conclusions: Co-administration of cilostazol and aspirin significantly ameliorates the immediate expression of the studied biomarkers. Further large-scale studies are needed to investigate the effect of combined therapy for primary and secondary prevention of stroke, using not only serum biomarkers but other specific clinical and laboratory endpoints. Full article

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

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11 pages, 5327 KiB

Open AccessCase Report

Coexisting Subdural Hematoma in Cerebral Amyloid Angiopathy: A Case Series

by Matija Zupan, Lara Straus, Tomaž Velnar, Matic Bošnjak, Ulf Jensen-Kondering, Bruno Splavski and Senta Frol

Neurol. Int. 2025, 17(8), 125; https://doi.org/10.3390/neurolint17080125 - 7 Aug 2025

Abstract

Background: Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage (ICH) in elderly individuals, and it is characterized by the deposition of amyloid β protein (Aß) in the walls of small-caliber cortical and leptomeningeal vessels. The diagnostic criteria for CAA [...] Read more.

Background: Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage (ICH) in elderly individuals, and it is characterized by the deposition of amyloid β protein (Aß) in the walls of small-caliber cortical and leptomeningeal vessels. The diagnostic criteria for CAA highlight its association with spontaneous lobar hemorrhage, convexity subarachnoid hemorrhage (SAH), and cortical superficial siderosis but not with subdural hematoma (SDH). This article presents a three-patient case series of CAA who experienced a lobar ICH associated with an SDH, underscoring a potentially under-recognized correlation between an acute ICH and coexistent SDH. Case presentation: We present a case series of three patients in a single university medical center who experienced acute-onset lobar ICH with a concurrent SDH, treated with evacuation. Histopathological examination established the diagnosis of CAA in all three cases. This case series underscores a potentially under-recognized association between an acute ICH and coexistent SDH in the context of CAA. Conclusions: Considering our findings, we emphasize the possibility that SDH may be a more frequent manifestation of CAA than previously recognized. Therefore, patients with CAA who initially present with acute SDH may be underdiagnosed, consequently leading to delayed identification and missed opportunities for proper risk assessment and management. Full article

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

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12 pages, 2779 KiB

Open AccessArticle

Clinical and Electrodiagnostic Correlations of Ultrasound-Detected Markedly Enlarged Median Nerve at the Wrist

by Lisa B. E. Shields, Vasudeva G. Iyer, Theresa Kluthe, Kahir Jawad, Jun Cai, Yi Ping Zhang and Christopher B. Shields

Neurol. Int. 2025, 17(8), 124; https://doi.org/10.3390/neurolint17080124 - 7 Aug 2025

Abstract

Background/Objectives: This is a retrospective review of 36 patients with electrodiagnostic (EDX) confirmation of carpal tunnel syndrome (CTS) and ultrasound (US) detection of marked median nerve enlargement (defined as a cross-sectional area [CSA] of 40 mm² or greater) at the wrist. Methods: [...] Read more.

Background/Objectives: This is a retrospective review of 36 patients with electrodiagnostic (EDX) confirmation of carpal tunnel syndrome (CTS) and ultrasound (US) detection of marked median nerve enlargement (defined as a cross-sectional area [CSA] of 40 mm² or greater) at the wrist. Methods: We describe the clinical, electrodiagnostic (EDX), and US findings in these patients and discuss the pathophysiologic basis of a markedly enlarged median nerve. Results: The markedly enlarged median nerve was detected by US in a total of 39 hands (36 patients, with 3 bilateral). Of the 39 hands, thenar atrophy was observed in 15 (38.5%) hands, and pinprick loss in the median nerve distribution was noted in all hands. Moderately severe or severe median nerve entrapment at the carpal tunnel (CT) was confirmed by EDX studies in 21 (53.8%) and 16 (41.0%) hands, respectively. A total of 12 (30.8%) hands had no compound muscle action potentials (CMAPs) over the abductor pollicis brevis muscle, and sensory nerve action potentials (SNAPs) were not detected in 31 (79.5%) hands. The wrist CSA was between 40 and 44 mm² in 20 (51.3%) hands, between 45 and 49 mm² in 13 (33.3%) hands, and 50 mm² or greater in 6 (15.4%) hands. Conclusions: The implications of the markedly enlarged median nerve for surgical management of CTS are unknown, and future prospective studies are needed. Full article

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

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14 pages, 1391 KiB

Open AccessArticle

Correlation of Neurodegenerative Biomarkers and Functional Outcome in Patients with Relapsing–Remitting Multiple Sclerosis

by Elina Polunosika, Monta Feldmane, Daina Pastare, Joel Simren, Kaj Blennow, Nauris Zdanovskis, Henrik Zetterberg, Renars Erts and Guntis Karelis

Neurol. Int. 2025, 17(8), 123; https://doi.org/10.3390/neurolint17080123 - 7 Aug 2025

Abstract

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament [...] Read more.

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL. Full article

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

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14 pages, 541 KiB

Open AccessReview

Foreign Language Syndrome: Neurological and Psychiatric Aspects

by Ansam Eghzawi, Ali Madha and Rany Aburashed

Neurol. Int. 2025, 17(8), 122; https://doi.org/10.3390/neurolint17080122 - 6 Aug 2025

Abstract

Foreign Language Syndrome (FLS) is a rare neuropsychiatric condition characterized by the sudden, involuntary use of a non-native language, with concurrent loss or suppression of the native language. Distinct from Foreign Accent Syndrome (FAS), FLS often arises acutely following anesthesia, brain injury, or [...] Read more.

Foreign Language Syndrome (FLS) is a rare neuropsychiatric condition characterized by the sudden, involuntary use of a non-native language, with concurrent loss or suppression of the native language. Distinct from Foreign Accent Syndrome (FAS), FLS often arises acutely following anesthesia, brain injury, or psychological stress. Although neuroimaging typically reveals no structural pathology, functional disconnection within bilingual language control systems has been hypothesized. Case reports suggest contributions from both neurological disruptions—such as transient cortical dysfunction—and psychiatric mechanisms, including dissociation and conversion phenomena. This review synthesizes the clinical features, diagnostic strategies, neurocognitive models, and psychiatric interpretations of FLS. It emphasizes the importance of multidisciplinary evaluation and treatment and outlines prognosis patterns. The need for longitudinal follow-up, functional imaging studies, and centralized case databases is highlighted to better understand the pathophysiology and clinical management of this enigmatic syndrome. Full article

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

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23 pages, 4728 KiB

Open AccessArticle

A Web-Deployed, Explainable AI System for Comprehensive Brain Tumor Diagnosis

by Serra Aksoy, Pinar Demircioglu and Ismail Bogrekci

Neurol. Int. 2025, 17(8), 121; https://doi.org/10.3390/neurolint17080121 - 4 Aug 2025

Abstract

Background/Objectives: Accurate diagnosis of brain tumors is one of the most important challenges in neuro-oncology since tumor classification and volumetric segmentation inform treatment planning. Two-dimensional classification and three-dimensional segmentation deep learning models can augment radiological workflows, particularly if paired with explainable AI techniques [...] Read more.

Background/Objectives: Accurate diagnosis of brain tumors is one of the most important challenges in neuro-oncology since tumor classification and volumetric segmentation inform treatment planning. Two-dimensional classification and three-dimensional segmentation deep learning models can augment radiological workflows, particularly if paired with explainable AI techniques to improve model interpretability. The objective of this research was to develop a web-based brain tumor segmentation and classification diagnosis platform. Methods: A diagnosis system was developed combining 2D tumor classification and 3D volumetric segmentation. Classification employed a fine-tuned MobileNetV2 model trained on a glioma, meningioma, pituitary tumor, and normal control dataset. Segmentation employed a SegResNet model trained on BraTS multi-channel MRI with synthetic no-tumor data. A meta-classifier MLP was used for binary tumor detection from volumetric features. Explainability was offered using XRAI maps for 2D predictions and Gaussian overlays for 3D visualizations. The platform was incorporated into a web interface for clinical use. Results: MobileNetV2 2D model recorded 98.09% classification accuracy for tumor classification. 3D SegResNet obtained Dice coefficients around 68–70% for tumor segmentations. The MLP-based tumor detection module recorded 100% detection accuracy. Explainability modules could identify the area of the tumor, and saliency and overlay maps were consistent with real pathological features in both 2D and 3D. Conclusions: Deep learning diagnosis system possesses improved brain tumor classification and segmentation with interpretable outcomes by utilizing XAI techniques. Deployment as a web tool and a user-friendly interface made it suitable for clinical usage in radiology workflows. Full article

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

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20 pages, 2238 KiB

Open AccessReview

The Pathogenesis and Medical Treatment of Depression: Opportunity and Challenge

by Mengjiao Xu, Zhiyu Zhang, Zhoudong Zhang, Dong Liu, Yanguo Shang, Chenglun Tang, Weipeng Wang, Huanqiu Li, Bengang You, Hanjie Ying and Tao Shen

Neurol. Int. 2025, 17(8), 120; https://doi.org/10.3390/neurolint17080120 - 4 Aug 2025

Abstract

Depression is a common mental disorder with high economic burden, characterized by high disability and mortality rates. The etiology of depression remains unclear to date, and there are various hypotheses regarding the pathogenesis of depression in clinical practice, including the monoamine neurotransmitter hypothesis, [...] Read more.

Depression is a common mental disorder with high economic burden, characterized by high disability and mortality rates. The etiology of depression remains unclear to date, and there are various hypotheses regarding the pathogenesis of depression in clinical practice, including the monoamine neurotransmitter hypothesis, the hypothalamic–pituitary–adrenal (HPA) axis dysregulation hypothesis, the inflammatory cytokine hypothesis, and the neurotrophic factor hypothesis. These theories offer specific directional aid in the clinical management of individuals suffering from depression. Medicinal intervention stands as a critical approach within the spectrum of depression treatments, and this article reviews the specific mechanisms of different hypotheses on the pathogenesis of depression in recent years, as well as the research progress on related therapeutic drugs. Full article

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13 pages, 2174 KiB

Open AccessArticle

Characterization of QuantiFERON-TB-Plus Results in Patients with Tuberculosis Infection and Multiple Sclerosis

by Elisa Petruccioli, Luca Prosperini, Serena Ruggieri, Valentina Vanini, Andrea Salmi, Gilda Cuzzi, Simonetta Galgani, Shalom Haggiag, Carla Tortorella, Gabriella Parisi, Alfio D’Agostino, Gina Gualano, Fabrizio Palmieri, Claudio Gasperini and Delia Goletti

Neurol. Int. 2025, 17(8), 119; https://doi.org/10.3390/neurolint17080119 - 2 Aug 2025

Abstract

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. [...] Read more.

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

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14 pages, 2132 KiB

Open AccessArticle

Measuring Myotonia: Normative Values and Comparison with Myotonic Dystrophy Type 1

by Andrea Sipos, Milán Árvai, Dávid Varga, Brigitta Ruszin-Perecz, József Janszky, Nándor Hajdú and Endre Pál

Neurol. Int. 2025, 17(8), 118; https://doi.org/10.3390/neurolint17080118 - 31 Jul 2025

Abstract

Introduction: Myotonia is a rare neuromuscular condition characterized by impaired muscle relaxation. In this study, we provide normative values for clinical tests related to myotonia in the Hungarian population and compare them to patients with myotonic dystrophy type 1 (DM1). Methods: Relaxation tests [...] Read more.

Introduction: Myotonia is a rare neuromuscular condition characterized by impaired muscle relaxation. In this study, we provide normative values for clinical tests related to myotonia in the Hungarian population and compare them to patients with myotonic dystrophy type 1 (DM1). Methods: Relaxation tests (10 eye openings, tongue extension, and palm openings), handgrip strength, and the nine-hole peg test were conducted on 139 healthy individuals and 31 patients with DM1. Results: We observed non-significant declines in handgrip strength and relaxation tests with age (p < 0.05). Significant differences were found between controls (n:139) and patients with DM1 (n = 31) in all tests (p < 0.05). Sex differences were noted in the healthy population: men (n:68/139) had stronger handgrip (mean of men 42.45 ± 1.15 vs. women 24.3 ± 0.9) and slower relaxation tests (mean of eye openings in men 3.6 ± 0.2 vs. in women 4.2 ± 0.2, tongue extensions in men 3.7 ± 0.2 vs. in women 4.2 ± 0.2, palm openings in men 4 ± 0.2 vs. in women 4.9 ± 0.2 However, these differences were not present among patients with DM1. Discussion: Normal values for relaxation tests across different age groups were established. These results might be useful for further clinical investigations. Our study supports the usage of averages of healthy population instead of age groups of relaxation tests and their clinical relevance in the evaluation of patients with myotonia. Full article

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

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13 pages, 1698 KiB

Open AccessReview

Systematic Review of Parkinsonism in Cerebrotendinous Xanthomatosis

by Jennifer Hanson and Penelope E. Bonnen

Neurol. Int. 2025, 17(8), 117; https://doi.org/10.3390/neurolint17080117 - 30 Jul 2025

Abstract

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some [...] Read more.

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX. Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to both chenodeoxycholic acid and dopaminergic medications were examined for 72 subjects. Results: The average age of onset of parkinsonism in these CTX patients was 42 years, illustrating the early onset nature of parkinsonism in CTX. Functional dopaminergic imaging revealed the loss of presynaptic dopaminergic neurons in the substantia nigra which points to neurodegeneration of the dopaminergic system as the underlying pathophysiology for parkinsonism in CTX. Brain MRI showed abnormalities in the basal ganglia in 38% of subjects. MRI also showed abnormalities in the cerebellum in 88% of subjects which is typical for CTX and can be utilized to distinguish subjects with CTX and parkinsonism from individuals with other forms of atypical parkinsonism. Dopaminergic medication mitigated parkinsonism signs in most individuals with CTX. Conclusion: CTX is a neurometabolic disease that can result in levodopa-responsive parkinsonism that should be included in the differential for atypical parkinsonism. Full article

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

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17 pages, 280 KiB

Open AccessArticle

Reliability and Validity of the Lowenstein Communication Scale

by Anna Oksamitni, Hiela Lehrer, Ilana Gelernter, Michal Scharf, Lilach Front, Olga Bendit-Goldenberg, Amiram Catz and Elena Aidinoff

Neurol. Int. 2025, 17(8), 116; https://doi.org/10.3390/neurolint17080116 - 29 Jul 2025

Abstract

Background/Objectives: The Lowenstein Communication Scale (LCS) is a tool for the evaluation of communicative performance in patients with disorders of consciousness (DOC). This study investigated the reliability and validity of the LCS. Methods: We evaluated 23 inpatients with unresponsive wakefulness syndrome (UWS) and [...] Read more.

Background/Objectives: The Lowenstein Communication Scale (LCS) is a tool for the evaluation of communicative performance in patients with disorders of consciousness (DOC). This study investigated the reliability and validity of the LCS. Methods: We evaluated 23 inpatients with unresponsive wakefulness syndrome (UWS) and 18 in a minimally conscious state (MCS), at admission to a Consciousness Rehabilitation Department and one month later. The evaluations included assessments of LCS by two raters, and of the Coma Recovery Scale–Revised (CRS-R) by one rater. Results: Total inter-rater agreement in LCS task scoring was found in 58–100% of the patients. Cohen’s kappa values were >0.6 for most tasks. High correlations were found between the two raters on total scores and most subscales (r = 0.599–1.000, p < 0.001), and the differences between them were small. LCS subscales and total score intraclass correlations (ICC) were high. Internal consistency was acceptable (Cronbach’s α > 0.7) for most LCS subscales and total scores. Moderate to strong correlations were found between LCS and CRS-R scores (r = 0.554–0.949, p < 0.05), and the difference in responsiveness between LCS and CRS-R was non-significant. Conclusions: The findings indicate that the LCS is reliable and valid, making it a valuable clinical and research assessment tool for patients with DOC. Full article

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

9 pages, 234 KiB

Open AccessReview

Endovascular Treatment of Stroke and Anesthesia Technique: What Is the Best Approach, According to the Literature?

by Federica Arturi, Gabriele Melegari, Fabio Gazzotti, Elisabetta Bertellini and Alberto Barbieri

Neurol. Int. 2025, 17(8), 115; https://doi.org/10.3390/neurolint17080115 - 25 Jul 2025

Abstract

Background/Objectives: Endovascular thrombectomy has become a mainstay in the treatment of acute ischemic stroke caused by large vessel occlusion. Among the multiple factors that influence outcomes, the choice of anesthetic technique—general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA)—remains controversial. This narrative [...] Read more.

Background/Objectives: Endovascular thrombectomy has become a mainstay in the treatment of acute ischemic stroke caused by large vessel occlusion. Among the multiple factors that influence outcomes, the choice of anesthetic technique—general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA)—remains controversial. This narrative review aims to critically examine and synthesize current evidence comparing the efficacy and safety of different anesthetic strategies in endovascular stroke treatment. Methods: A structured search of the PubMed^® database was conducted using the terms “stroke treatment”, “endovascular stroke treatment”, “anesthesia”, “general anesthesia”, “conscious sedation”, and “local anesthesia”. The search focused on clinical trials involving human subjects published in English. Studies were included if they compared at least two anesthetic techniques during thrombectomy and reported outcomes such as neurological recovery, mortality, or complication rates. Reviews, case reports, and animal studies were excluded. Results: Several randomized controlled trials and observational studies show comparable functional outcomes between GA and CS, though CS may confer advantages in early neurological recovery and reduced complications. Local anesthesia, though less studied, may offer favorable outcomes in selected patients. General anesthesia appears to be associated with greater hemodynamic variability and a higher risk of post-procedural infections, particularly in unsuccessful interventions. Maintaining stable blood pressure and minimizing ventilation duration are crucial to improving patient prognosis. Conclusions: While both GA and CS are viable options during thrombectomy, CS and LA may provide a safer profile in selected patients by preserving hemodynamic stability and reducing infectious risk. Personalized anesthetic strategies and further high-quality trials are warranted. Full article

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

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Graphical abstract

9 pages, 550 KiB

Open AccessBrief Report

Elevated Urinary Titin in Adult Spinal Muscular Atrophy: A Multicenter, Cross-Sectional Observational Study

by Andrea Sipos, Emese Rebeka Ripszám, Judit Mária Molnár, Zoltán Grosz, Judit Boczán, Melinda Borbála Altorjay, Livia Dézsi, Anett Csáti, Kristóf Babarczy, Norbert Kovács, Nándor Hajdú and Endre Pál

Neurol. Int. 2025, 17(8), 114; https://doi.org/10.3390/neurolint17080114 - 22 Jul 2025

Abstract

Background: Spinal muscular atrophy (SMA) is a treatable motor neuron disease. Biomarkers for skeletal muscle atrophy are extremely important for measuring the effects of treatment and monitoring the natural course of the disease. The urinary titin N fragment (UNT) has recently been proven [...] Read more.

Background: Spinal muscular atrophy (SMA) is a treatable motor neuron disease. Biomarkers for skeletal muscle atrophy are extremely important for measuring the effects of treatment and monitoring the natural course of the disease. The urinary titin N fragment (UNT) has recently been proven to be related to muscle damage. Methods: The UNT was measured in 41 patients with SMA and 41 healthy controls. Clinical data, functional tests, and laboratory findings were also recorded. Results: We found significantly higher UNT levels in the patient samples than in the healthy subjects. The UNT was not related to disease type, functional test results, or serum creatine kinase levels. Conclusions: This cross-sectional study highlights the importance of the UNT as a potential noninvasive biomarker for spinal muscular atrophy. Its role can potentially be verified through longitudinal studies. Full article

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

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34 pages, 1079 KiB

Open AccessSystematic Review

The Central Variant of Posterior Reversible Encephalopathy Syndrome: A Systematic Review and Meta-Analysis

by Bahadar S. Srichawla, Maria A. Garcia-Dominguez and Brian Silver

Neurol. Int. 2025, 17(7), 113; https://doi.org/10.3390/neurolint17070113 - 21 Jul 2025

Abstract

Background: The central variant of posterior reversible encephalopathy syndrome (cvPRES) is an atypical subtype of PRES. Although no unifying definitions exists, it is most often characterized by vasogenic edema involving “central” structures, such as the brainstem, subcortical nuclei, and spinal cord, with relative [...] Read more.

Background: The central variant of posterior reversible encephalopathy syndrome (cvPRES) is an atypical subtype of PRES. Although no unifying definitions exists, it is most often characterized by vasogenic edema involving “central” structures, such as the brainstem, subcortical nuclei, and spinal cord, with relative sparing of the parieto-occipital lobes. Methods: This systematic review and meta-analysis followed the PRISMA guidelines and was pre-registered on PROSPERO [CRD42023483806]. Both the Joanna Briggs Institute and New-Castle Ottawa scale were used for case reports and cohort studies, respectively. The meta-analysis was completed using R-Studio and its associated “metafor” package. Results: A comprehensive search in four databases yielded 70 case reports/series (n = 100) and 12 cohort studies. The meta-analysis revealed a pooled incidence rate of 13% (95% CI: 9–18%) for cvPRES amongst included cohort studies on PRES. Significant heterogeneity was observed (I² = 71% and a τ² = 0.2046). The average age of affected individuals was 40.9 years, with a slightly higher prevalence in males (54%). The most common etiological factor was hypertension (72%). Fifty percent had an SBP >200 mmHg at presentation and a mean arterial pressure (MAP) of 217.6 ± 40.82. Imaging revealed an increased T₂ signal involving the brain stem (88%), most often in the pons (62/88; 70.45%), and 18/100 (18%) cases of PRES with spinal cord involvement (PRES-SCI). Management primarily involved blood pressure reduction, with adjunctive therapies for underlying causes such as anti-seizure medications or hemodialysis. The MAP between isolated PRES-SCI and cvPRES without spinal cord involvement did not show significant differences (p = 0.5205). Favorable outcomes were observed in most cases, with a mortality rate of only 2%. Conclusions: cvPRES is most often associated with higher blood pressure compared to prior studies with typical PRES. The pons is most often involved. Despite the severity of blood pressure and critical brain stem involvement, those with cvPRES have favorable functional outcomes and a lower mortality rate than typical PRES, likely attributable to reversible vasogenic edema without significant neuronal dysfunction. Full article

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13 pages, 736 KiB

Open AccessReview

An Overview About Figure-of-Eight Walk Test in Neurological Disorders: A Scoping Review

by Gabriele Triolo, Roberta Lombardo, Daniela Ivaldi, Angelo Quartarone and Viviana Lo Buono

Neurol. Int. 2025, 17(7), 112; https://doi.org/10.3390/neurolint17070112 - 21 Jul 2025

Abstract

Introduction: The figure-of-eight walk test (F8WT) assesses gait on a curved path, reflecting everyday walking complexity. Despite recognized validity among elderly individuals, its application in neurological disorders remains inadequately explored. This scoping review summarizes evidence regarding F8WT use, validity, and clinical applicability among [...] Read more.

Introduction: The figure-of-eight walk test (F8WT) assesses gait on a curved path, reflecting everyday walking complexity. Despite recognized validity among elderly individuals, its application in neurological disorders remains inadequately explored. This scoping review summarizes evidence regarding F8WT use, validity, and clinical applicability among individuals with neurological disorders. Methods: A systematic literature search was conducted in the PubMed, Scopus, Embase, and Web of Science databases. After reading the full text of the selected studies and applying predefined inclusion criteria, seven studies, involving participants with multiple sclerosis (n = 3 studies), Parkinson’s disease (n = 2 studies), and stroke (n = 2 studies), were included based on pertinence and relevance to the topic. Results: F8WT demonstrated strong reliability and validity across various neurological populations and correlated significantly with established measures of gait, balance, and disease severity. Preliminary evidence supports its ability to discriminate individuals at increased fall risk and detect subtle motor performance changes. Discussion: The F8WT emerges as a valuable tool, capturing multifaceted gait impairments often missed by linear walking assessments. Sensitive to subtle functional changes, it is suitable for tracking disease progression and intervention efficacy. Conclusions: F8WT is reliable and clinically relevant, effectively identifying subtle, complex walking impairments in neurological disorders. Full article

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

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16 pages, 624 KiB

Open AccessArticle

Selective Serotonin Reuptake Inhibitor-Associated Intracranial Hemorrhage: Drug-Specific Risk Patterns and Patient-Level Modifiers

by Josef Yayan and Kurt Rasche

Neurol. Int. 2025, 17(7), 111; https://doi.org/10.3390/neurolint17070111 - 18 Jul 2025

Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance [...] Read more.

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article

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16 pages, 1269 KiB

Open AccessArticle

The Association of Axonal Damage Biomarkers and Osteopontin at Diagnosis Could Be Useful in Newly Diagnosed MS Patients

by Eleonora Virgilio, Chiara Puricelli, Nausicaa Clemente, Valentina Ciampana, Ylenia Imperatore, Simona Perga, Sveva Stangalini, Elena Boggio, Alice Appiani, Casimiro Luca Gigliotti, Umberto Dianzani, Cristoforo Comi and Domizia Vecchio

Neurol. Int. 2025, 17(7), 110; https://doi.org/10.3390/neurolint17070110 - 17 Jul 2025

Abstract

(1) Background: Multiple sclerosis (MS) is a biologically highly heterogeneous disease and has poor predictability at diagnosis. Moreover, robust data indicate that early disease activity strongly correlates with future disability. Therefore, there is a need for strong and reliable biomarkers from diagnosis to [...] Read more.

(1) Background: Multiple sclerosis (MS) is a biologically highly heterogeneous disease and has poor predictability at diagnosis. Moreover, robust data indicate that early disease activity strongly correlates with future disability. Therefore, there is a need for strong and reliable biomarkers from diagnosis to characterize and identify patients who require highly effective disease-modifying treatments (DMTs). Several biomarkers are promising, particularly neurofilament light chains (NFLs), but the relevance of others is less consolidated. (2) Methods: We evaluated a panel of axonal damage and inflammatory biomarkers in cerebrospinal fluid (CSF) and matched serum obtained from a cohort of 60 newly diagnosed MS patients. Disability at diagnosis, negative prognostic factors, and the initial DMT prescribed were carefully recorded. (3) Results: We observed correlations between different axonal biomarkers: CSF and serum NFL versus CSF total tau; and between the inflammatory marker osteopontin (OPN) and axonal biomarkers CSF p-Tau, CSF total tau, and serum NFL. CSF and serum NFL and total tau, as well as CSF OPN, positively correlated with EDSS at diagnosis. Moreover, CSF and serum NFL levels were increased in patients with gadolinium-enhancing lesions (p = 0.01 and p = 0.04, respectively) and in those treated with highly effective DMT (p = 0.049). Furthermore, CSF OPN and both CSF and serum NFL levels significantly differentiated patients based on EDSS, with a combined ROC AUC of 0.88. We calculated and internally validated biomarker (in particular serum NFL) thresholds that significantly identified patients with higher disability. Finally, CSF OPN levels and dissemination in the spinal cord were significant predictors of EDSS at diagnosis. (4) Conclusions: These preliminary exploratory data confirm the pathological interconnection between inflammation and axonal damage from early disease stages, contributing to early disability. Follow-up data, such as longitudinal disability scores, repeated serum measurements, a healthy control group, and external validation of our results, are needed. We suggest that combining several fluid biomarkers may improve the clinical characterization of patients. Full article

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

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13 pages, 974 KiB

Open AccessArticle

G-Protein-Coupled Estrogen Receptor (GPER) in Inflammatory Myopathies

by Delia Righi, Diego Lopergolo, Nila Volpi, Daniela Franci, Paola Lorenzoni, Margherita Aglianò, Gianna Berti, Carlo Manco, Nicola De Stefano and Federica Ginanneschi

Neurol. Int. 2025, 17(7), 109; https://doi.org/10.3390/neurolint17070109 - 17 Jul 2025

Abstract

Background/Objectives: Given the multifaceted role of estrogen hormones in skeletal muscle pathophysiology and their well-established immunomodulatory properties, this study aimed to characterize the expression of the G-protein-coupled estrogen receptor (GPER) in patients with inflammatory myopathies (IM). Methods: Immunohistochemical analysis was performed [...] Read more.

Background/Objectives: Given the multifaceted role of estrogen hormones in skeletal muscle pathophysiology and their well-established immunomodulatory properties, this study aimed to characterize the expression of the G-protein-coupled estrogen receptor (GPER) in patients with inflammatory myopathies (IM). Methods: Immunohistochemical analysis was performed on muscle biopsies from 13 patients with IM, 11 with non-inflammatory myopathies (N.IM), and 5control subjects. Intergroup differences in GPER score were statistically evaluated. We performed an analysis based on the Visual Analog Scale (VAS). The scoring system evaluates overall pathology (VAS score) based on four distinct components: inflammation, vascular involvement, myopathic changes, and connective tissue alterations. Results: Immunolocalization analysis demonstrated that GPER is constitutively expressed in human skeletal muscle and is upregulated in IM. Enhanced expression included both sarcolemmal and intracellular membrane localization. Notably, GPER upregulation showed a positive correlation with the severity of tissue inflammation. The IM group had significantly higher VAS scores compared to both the N.IM and control groups. Conclusions: We provide the first histopathological characterization of GPER expression in human skeletal muscle. In IM, GPER upregulation may play a protective role by negatively modulating the release of inflammatory mediators, as suggested by experimental evidence from other models of inflammation. The emerging therapeutic development of GPER agonists may represent a promising avenue for the treatment of inflammatory myopathies. Full article

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17 pages, 1455 KiB

Open AccessArticle

Effectiveness of a Cognitive Stimulation Program in Older Adults with Mild Neurocognitive Disorder: Insights from fNIRS Analysis in a Randomized Controlled Trial

by Susana I. Justo-Henriques, Rosa C. G. Silva, Janessa O. Carvalho, João L. A. Apóstolo, Débora Nogueira and Telmo A. S. Pereira

Neurol. Int. 2025, 17(7), 108; https://doi.org/10.3390/neurolint17070108 - 15 Jul 2025

Abstract

Background/Objectives: Neurocognitive disorders (NCDs) encompass a spectrum of conditions that significantly impact cognitive domains, including attention, memory, and language. Mild NCD, increasingly prevalent with aging, represents an early stage of these disorders, characterized by cognitive deficits that do not interfere with daily functioning. [...] Read more.

Background/Objectives: Neurocognitive disorders (NCDs) encompass a spectrum of conditions that significantly impact cognitive domains, including attention, memory, and language. Mild NCD, increasingly prevalent with aging, represents an early stage of these disorders, characterized by cognitive deficits that do not interfere with daily functioning. Non-pharmacological therapies, especially cognitive stimulation, are widely recommended to preserve cognitive function of older adults. This study aimed to evaluate the effectiveness of a 12-week individual cognitive stimulation (iCS) program on cognitive performance, mood, and prefrontal cortex activation in older adults with mild NCD using a single-blind, randomized, parallel two-arm RCT. Methods: A sample of 36 older adults were selected from a central region of Portugal. The intervention group (n = 18) received 24 iCS sessions, twice weekly for 12 weeks. The control group (n = 18) completed their regularly scheduled activities. Outcomes included global cognitive function, executive functioning, and mood. All participants were assessed at baseline and after the intervention. Functional near infra-red spectroscopy (fNIRS) was also collected to measure prefrontal cortex activity at both time points in the intervention group. Results: The intervention group showed a significant improvement in global cognition and executive functions, and reduced depressive symptomatology compared to the control group. fNIRS data revealed enhanced activation and functional efficiency in the lateral prefrontal cortex following the iCS program. Adherence and degree of collaboration to the intervention were very high. Conclusions: These findings suggest that iCS is an effective approach to improving cognitive function and mood in mildly cognitively impaired older adults. Full article

(This article belongs to the Section Aging Neuroscience)

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