Journal Description
Neurology International
Neurology International
is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of neurology and neuroscience, published monthly online by MDPI (from Volume 12 issue 3 - 2020). The Panhellenic Federation of Alzheimer's Disease and Related Disorders is affiliated with Neurology International and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, Embase, and other databases.
- Journal Rank: JCR - Q2 (Clinical Neurology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 21.4 days after submission; acceptance to publication is undertaken in 3.8 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Journal Cluster of Neurosciences: Brain Sciences, Neurology International, NeuroSci, Clinical and Translational Neuroscience, Neuroglia, Psychiatry International, Clocks & Sleep and Journal of Dementia and Alzheimer's Disease.
Impact Factor:
3.0 (2024);
5-Year Impact Factor:
3.3 (2024)
Latest Articles
A Web-Deployed, Explainable AI System for Comprehensive Brain Tumor Diagnosis
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)
►
Show Figures
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
►▼
Show Figures
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

Figure 1
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
►▼
Show Figures
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

Figure 1
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)
►▼
Show Figures

Figure 1
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)
►▼
Show Figures

Figure 1
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)
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)
►▼
Show Figures

Graphical abstract
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)
►▼
Show Figures

Figure 1
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
►▼
Show Figures
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

Graphical abstract
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)
►▼
Show Figures

Figure 1
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
►▼
Show Figures
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

Figure 1
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)
►▼
Show Figures

Figure 1
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
►▼
Show Figures
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

Figure 1
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)
►▼
Show Figures

Figure 1
Open AccessReview
Cognitive Effects of Cannabis Use: A Comprehensive Review Across Domains
by
Andréia Pucinelli de Souza Queiroz, Maria Olivia Pozzolo Pedro, Marcela Waisman Campos, Julio Torales, Antonio Ventriglio and João Mauricio Castaldelli-Maia
Neurol. Int. 2025, 17(7), 107; https://doi.org/10.3390/neurolint17070107 - 15 Jul 2025
Abstract
►▼
Show Figures
Cannabis is the most widely consumed illicit substance worldwide, with rising use particularly among adolescents and young adults. Accumulating evidence indicates that chronic cannabis use may negatively impact several domains of cognition, yet findings across studies remain varied and fragmented. This comprehensive review
[...] Read more.
Cannabis is the most widely consumed illicit substance worldwide, with rising use particularly among adolescents and young adults. Accumulating evidence indicates that chronic cannabis use may negatively impact several domains of cognition, yet findings across studies remain varied and fragmented. This comprehensive review synthesizes current knowledge on the long-term cognitive consequences of cannabis use, focusing on attention, executive functioning, learning, memory, language, motor coordination, and social cognition. Consistent impairments have been observed in domains such as attention, executive function, memory, and learning; however, most evidence derives from studies of acute or residual effects. Evidence of long-lasting deficits after extended abstinence remains more limited and methodologically heterogeneous. Acute motor coordination deficits are well established, but persistent impairments in this domain lack conclusive evidence. Effects on language remain inconclusive, and findings regarding social cognition, though limited, suggest potential deficits in emotion recognition and mental state inference. Early onset and high-frequency use are critical risk factors for more severe and enduring cognitive effects. Some deficits may partially reverse with abstinence, although many persist long after cessation. Overall, cannabis use is associated with widespread and lasting cognitive impairments. These findings underscore the need for targeted prevention strategies, especially among youth, and point to future longitudinal and mechanistic research to better understand the nature, persistence, and potential reversibility of these cognitive effects.
Full article

Figure 1
Open AccessReview
Implications for the Ergogenic Benefits of Self-Selected Music in Neurological Conditions: A Theoretical Review
by
Christopher G. Ballmann, Rebecca R. Rogers, Sophia L. Porrill and Nicholas B. Washmuth
Neurol. Int. 2025, 17(7), 106; https://doi.org/10.3390/neurolint17070106 - 11 Jul 2025
Abstract
The ergogenic effects of music have been well described across various modes of exercise with widespread use across competitive athletes and recreational exercisers alike. Underlying the acute beneficial effects of music during exercise are profound physiological and psychological changes which involve an array
[...] Read more.
The ergogenic effects of music have been well described across various modes of exercise with widespread use across competitive athletes and recreational exercisers alike. Underlying the acute beneficial effects of music during exercise are profound physiological and psychological changes which involve an array of different organ systems, including but not limited to cardiovascular, endocrine, skeletal muscle, and nervous systems. While the use of music to enhance physical performance and improve associated mechanisms has been largely optimized in healthy individuals, the investigations of the translation to individuals with neurological conditions are still ongoing. Recently, it has been established that the personalization of music interventions greatly influences performance-enhancing benefits and aids in physical performance optimization in healthy individuals. Self-selected music (SSM) has been documented to impart ergogenic advantages over pre-determined or non-preferred music, including improved cardiorespiratory endurance, power development, and velocity of movement which are characterized by adaptative physiological and psychological changes. Evidence of the benefits of SSM has progressed to the degree to which the overlap of possible benefits between healthy and clinical populations is becoming more apparent. This aim of this theoretical review is to discuss how personalized music influences psychophysiological determinants of exercise ability in healthy individuals and consider how these findings may be applicable to neurological conditions to enhance exercise capacity. The current knowledge on the role of SSM in augmenting physiological and psychological responses to exercise in healthy individuals is presented along with how these mechanisms might be leveraged to overcome exercise limitations in neurological conditions. Overall, SSM appears to have theoretical support to be a promising therapeutic approach to improving exercise ability in neurological conditions through similar ergogenic mechanisms documented in healthy individuals, but further investigation is warranted.
Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
►▼
Show Figures

Figure 1
Open AccessArticle
Visual Perception and Fixation Patterns in an Individual with Ventral Simultanagnosia, Integrative Agnosia and Bilateral Visual Field Loss
by
Isla Williams, Andrea Phillipou, Elsdon Storey, Peter Brotchie and Larry Abel
Neurol. Int. 2025, 17(7), 105; https://doi.org/10.3390/neurolint17070105 - 10 Jul 2025
Abstract
►▼
Show Figures
Background/Objectives: As high-acuity vision is limited to a very small visual angle, examination of a scene requires multiple fixations. Simultanagnosia, a disorder wherein elements of a scene can be perceived correctly but cannot be integrated into a coherent whole, has been parsed into
[...] Read more.
Background/Objectives: As high-acuity vision is limited to a very small visual angle, examination of a scene requires multiple fixations. Simultanagnosia, a disorder wherein elements of a scene can be perceived correctly but cannot be integrated into a coherent whole, has been parsed into dorsal and ventral forms. In ventral simultanagnosia, limited visual integration is possible. This case study was the first to record gaze during the presentation of a series of visual stimuli, which required the processing of local and global elements. We hypothesised that gaze patterns would differ with successful processing and that feature integration could be disrupted by distractors. Methods: The patient received a neuropsychological assessment and underwent CT and MRI. Eye movements were recorded during the following tasks: (1) famous face identification, (2) facial emotion recognition, (3) identification of Ishihara colour plates, and (4) identification of both local and global letters in Navon composite letters, presented either alone or surrounded by filled black circles, which we hypothesised would impair global processing by disrupting fixation. Results: The patients identified no famous faces but scanned them qualitatively normally. The only emotion to be consistently recognised was happiness, whose scanpath differed from the other emotions. She identified none of the Ishihara plates, although her colour vision was normal on the FM-15, even mapping an unseen digit with fixations and tracing it with her finger. For plain Navon figures, she correctly identified 20/20 local and global letters; for the “dotted” figures, she was correct 19/20 times for local letters and 0/20 for global letters (chi-squared NS for local, p < 0.0001, global), with similar fixation of salient elements for both. Conclusions: Contrary to our hypothesis, gaze behaviour was largely independent of the ability to process global stimuli, showing for the first time that normal acquisition of visual information did not ensure its integration into a percept. The core defect lay in processing, not acquisition. In the novel Navon task, adding distractors abolished feature integration without affecting the fixation of the salient elements, confirming for the first time that distractors could disrupt the processing, not the acquisition, of visual information in this disorder.
Full article

Figure 1
Open AccessBrief Report
Susceptibility Weighted Imaging in Migraines with and Without Aura: A Case–Control Study
by
Adrian Scutelnic, Tomas Klail, Diego Moor, Nedelina Slavova, Valentina Petroulia, Simon Jung, Mattia Branca, Urs Fischer, Franz Riederer, Roland Wiest and Christoph J. Schankin
Neurol. Int. 2025, 17(7), 104; https://doi.org/10.3390/neurolint17070104 - 8 Jul 2025
Abstract
Background: The asymmetry of cortical veins in susceptibility weighted imaging (SWI) in MRI might be a biomarker for migraine auras and cortical spreading depression (CSD). The aim of this study was to assess in humans if SWI asymmetry can be found in patients
[...] Read more.
Background: The asymmetry of cortical veins in susceptibility weighted imaging (SWI) in MRI might be a biomarker for migraine auras and cortical spreading depression (CSD). The aim of this study was to assess in humans if SWI asymmetry can be found in patients who have migraine attacks without auras. Methods: We included patients (n = 100 per group) from the emergency room setting when they (i) presented with an acute neurological deficit or headache; (ii) had a discharge diagnosis of a migraine aura, a migraine without an aura, or neither (controls without stroke or epilepsy); and (iii) had a brain MRI with SWI in the acute setting. Results: In the migraines with auras group, SWI asymmetry was found in 26% (95% CI 18–35) compared to patients with migraines without auras (3%, [95% CI 1–8], p < 0.001) and controls 7% [95% CI 3–14], p < 0.001). There was no difference between patients with migraines without auras and controls (p = 0.19). Conclusions: The distinct SWI changes in migraines with and without auras suggest that CSD might not be involved in the pathophysiology of migraines without auras.
Full article
(This article belongs to the Section Pain Research)
►▼
Show Figures

Figure 1
Open AccessArticle
Viscoelastic Point-of-Care Testing (ClotPro®) to Guide Intravenous Thrombolysis in Acute Ischemic Stroke Patients on DOACs: Replacing History with Hemostasis in a Proof-of-Concept Study
by
Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák, Eszter Johanna Jozifek and László Szapáry
Neurol. Int. 2025, 17(7), 103; https://doi.org/10.3390/neurolint17070103 - 1 Jul 2025
Abstract
Background: Administering intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) on direct oral anticoagulants (DOACs) remains a clinical challenge. Current guidelines restrict IVT within 48 h of DOAC intake unless anticoagulant activity can be confidently excluded. However, reliable medication histories are
[...] Read more.
Background: Administering intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) on direct oral anticoagulants (DOACs) remains a clinical challenge. Current guidelines restrict IVT within 48 h of DOAC intake unless anticoagulant activity can be confidently excluded. However, reliable medication histories are often unavailable, and conventional coagulation tests inadequately detect DOAC activity. This study evaluated whether viscoelastic point-of-care testing (ClotPro®) could identify the absence of anticoagulant effect in AIS patients on DOACs, thus enabling IVT administration and potentially improving clinical outcomes. Methods: We conducted a prospective observational cohort study of 40 AIS patients with documented DOAC use, admitted between February 2023 and May 2025. ClotPro® was performed at admission using the Russell’s viper venom (RVV) assay for factor Xa inhibitors and the ecarin clotting time (ECT) assay for dabigatran. Subtherapeutic anticoagulation was defined as a clotting time (CT) of <100 s for RVV and <180 s for ECT, respectively. Patients identified as being subtherapeutic were assessed for IVT eligibility. To evaluate IVT effects, we performed propensity score-matched bootstrap resampling (1000 iterations), matching patients by age, admission National Institutes of Health Stroke Scale (NIHSS), and pre-stroke modified Rankin Scale (mRS). Primary endpoints were NIHSS-shift (change from admission to 72 h) and mRS-shift (change from pre-stroke mRS to 90-day mRS). Predictors of outcomes were analyzed using multivariate regression models. Results: ClotPro® identified 15/40 patients (37.5%) as subtherapeutic, all on factor Xa inhibitors. Of these, seven received IVT. In matched analyses, IVT-treated patients showed a numerically greater neurological improvement than untreated patients (mean NIHSS-shift: −2.83 vs. 3.94; mean difference: −6.76, 95% confidence interval [CI]: −24.00 to 7.55; p = 0.495). Functional outcome by mRS-shift showed only minor differences between groups (2.74 vs. 2.10 mean difference: 0.64; 95% CI: −2.00 to 2.50; p = 0.510). IVT showed a favorable trend for early neurological recovery (p = 0.081) but was not independently associated with functional outcome (p = 0.380). Conclusions: ClotPro® identified a substantial subset of AIS patients on DOAC therapy without measurable anticoagulant activity, enabling IVT in cases that would otherwise have been excluded based on medication history. These findings support the feasibility of ClotPro®-guided decision-making in acute stroke care and highlight its potential to improve IVT selection by enabling real-time assessment of coagulation status at the bedside.
Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
Open AccessArticle
Exploratory Evaluation for Functional Changes of Six-Month Systematic Non-Invasive Electrical Stimulation in a Whole-Body Suit on Children with Cerebral Palsy GMFCS III–V
by
Tina P. Torabi, Kristian Mortensen, Josephine S. Michelsen and Christian Wong
Neurol. Int. 2025, 17(7), 102; https://doi.org/10.3390/neurolint17070102 - 30 Jun 2025
Abstract
Background/Objectives: Spasticity in children with cerebral palsy (CP) can impair motor-related functions. The objective of this exploratory, prospective study was to examine if transcutaneous electrical nerve stimulation (TENS) in a whole-body suit leads to changes in spasticity and other related effects. Methods: Thirty-one
[...] Read more.
Background/Objectives: Spasticity in children with cerebral palsy (CP) can impair motor-related functions. The objective of this exploratory, prospective study was to examine if transcutaneous electrical nerve stimulation (TENS) in a whole-body suit leads to changes in spasticity and other related effects. Methods: Thirty-one children with CP GMFCS III–V, with a median age of 11.0 years (age range of 7–17 years), were consecutively included, and they used the suit with TENS for 24 weeks. The primary outcome was spasticity measured using the Modified Ashworth Scale (MAS). Functional motor-related tasks were evaluated by the Goal Attainment Scale (SMART GAS). The Modified Tardieu Scale (MTS), passive Range of Motion (pROM), GMFM-66, and Posture and Postural Ability Scale (PPAS) assessments were performed. Results: Seventeen subjects (17/31) completed the 24 weeks. Dropout was due to difficulty in donning the suit. The level of overall spasticity, most pronounced in the proximal arms and legs, was reduced according to the MAS, but not the MTS or pROM. Subject-relevant motor-related goals improved significantly in standing/walking and hand/arm function. Changes in the GMFM-66 and PPAS were not significant. Conclusions: Although there were statistically significant but underpowered changes in the MAS after 24 weeks, there were no clinically relevant effects. Exploratorily, we found observer-reliant motor-related functional improvements, which, however, we were unable to detect when trying to quantify them. Donning the suit led to dropout throughout the study. Caregivers need to allocate time, mental capacity and have the physical skill set for donning the suit for long-term use.
Full article
(This article belongs to the Special Issue New Insights into Movement Disorders)
►▼
Show Figures

Figure 1

Journal Menu
► ▼ Journal Menu-
- Neurology International Home
- Aims & Scope
- Editorial Board
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Brain Sciences, Neurology International, NeuroSci
Research Advances in Psychiatric Diseases: Focusing on the Prediction of Suicide
Topic Editors: Maria Skibińska, Monika Wiłkość-Dębczyńska, Przemysław ZakowiczDeadline: 15 September 2025
Topic in
Brain Sciences, Neurology International, NeuroSci
Management of Multiple Sclerosis: Past, Present and Promise
Topic Editors: Salvatore Iacono, Paolo RagoneseDeadline: 5 November 2025
Topic in
Brain Sciences, Neurology International, NeuroSci
The Relationship Between Bodily, Autonomic, and Communicative Behaviors and the Experiential and Cognitive Aspects of Emotion
Topic Editors: Elliott D. Ross, Guido GainottiDeadline: 25 November 2025
Topic in
Brain Sciences, Neurology International, NeuroSci
The Interplay of the Brain, Behavior, and Immunity: Insights and Innovations
Topic Editors: Marinella Coco, Ashutosh TripathiDeadline: 10 December 2025

Conferences
Special Issues
Special Issue in
Neurology International
Acute and Chronic Pain: Pathogenesis, Treatment Strategies and Care
Guest Editors: Luca Gregorio Giaccari, Pasquale SansoneDeadline: 30 August 2025
Special Issue in
Neurology International
Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery
Guest Editor: Sonu M. M. BhaskarDeadline: 30 October 2025
Special Issue in
Neurology International
Advances in Molecular Mechanisms of Neurodegenerative Diseases
Guest Editors: Pravin Hivare, Joshna Gadhavi, Cristoforo ComiDeadline: 30 November 2025
Special Issue in
Neurology International
Beyond the Brain: Neurological Involvement in Pediatric Systemic Diseases
Guest Editor: Andrea Domenico PraticòDeadline: 30 November 2025
Topical Collections
Topical Collection in
Neurology International
Brain Health Initiative: Advocacy in Global Neurology
Collection Editors: Tissa Wijeratne, Leila Karimi, Dilani Wijeratne
Topical Collection in
Neurology International
Advances in Neurodegenerative Diseases
Collection Editors: Vasileios Siokas, Efthimios Dardiotis
Topical Collection in
Neurology International
Biomarkers in Stroke Prognosis
Collection Editors: Dimitrios Tsiptsios, Konstantinos Vadikolias
Topical Collection in
Neurology International
Exclusive Papers from the Editorial Board Members (EBMs) of Neurology InternationalCollection Editor: Junji Yamauchi