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).
- 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
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
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
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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
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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)
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Open AccessArticle
Sleep Disturbances and Obstructive Sleep Apnea in Children and Adolescents with Cerebral Palsy: An Observational Study
by
Isabella Meneses da Silva, Maria Clara Helena do Couto, Sanseray da Silveira Cruz-Machado, Leticia Monteiro de Andrade, Ana Elisa Zuliani Stroppa Marques, Celia Maria Giacheti, Cristiane Rodrigues Pedroni and Luciana Pinato
Neurol. Int. 2025, 17(7), 101; https://doi.org/10.3390/neurolint17070101 - 30 Jun 2025
Abstract
Background/Objectives: Cerebral palsy (CP) is a neurodevelopmental disorder associated with sleep disturbances, particularly sleep-disordered breathing (SDB), and is often linked to an increased risk of obstructive sleep apnea (OSA). OSA is underdiagnosed in this population due to the lack of standardized methods and
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Background/Objectives: Cerebral palsy (CP) is a neurodevelopmental disorder associated with sleep disturbances, particularly sleep-disordered breathing (SDB), and is often linked to an increased risk of obstructive sleep apnea (OSA). OSA is underdiagnosed in this population due to the lack of standardized methods and limited access to appropriate diagnostic technologies and appropriate equipment. Thus, this study aimed to investigate the presence and severity of sleep disorders, with a particular focus on OSA, in children and adolescents with CP compared to their typically developing peers. Methods: This observational, clinical, and prospective study included 28 children and adolescents with CP and 32 age- and sex-matched typically developing individuals. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (SDSC) and a high-resolution oximeter plus actigraphy combined with a cloud-based algorithm for the detection of obstructive sleep apnea (Biologix® system), which provided data on oxygen saturation, snoring, movement during sleep, and total sleep time. Results: According to the SDSC, 92% of children and adolescents with CP presented scores indicative of sleep disturbances, compared to 31% of typically developing individuals. SDB was the most prevalent subtype (64%) and overnight oximetry revealed that 100% of the CP group presented oxygen desaturation index (ODI) values consistent with a diagnosis of OSA. The CP group also exhibited significantly lower mean SpO2, longer snoring duration, shorter total sleep time, and prolonged sleep latency compared to the typically developing group. Conclusions: Children and adolescents with cerebral palsy (CP) exhibit a high prevalence of sleep disturbances, with increasing evidence indicating a significant occurrence of sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA).
Full article
Open AccessArticle
Perioperative Predictors of Early Spinal Cord Stimulator Removal: A Retrospective Cohort Study
by
Peyton J. Murin, Patrick J. Murin, Sejal V. Jain and Yuri Chaves Martins
Neurol. Int. 2025, 17(7), 100; https://doi.org/10.3390/neurolint17070100 - 27 Jun 2025
Abstract
Background: Spinal cord stimulators can offer an effective treatment in chronic pain refractory to conventional medical management. However, with a failure rate of up to 44% and an annual explantation rate of 6–9%, there is a need to better identify patients at high
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Background: Spinal cord stimulators can offer an effective treatment in chronic pain refractory to conventional medical management. However, with a failure rate of up to 44% and an annual explantation rate of 6–9%, there is a need to better identify patients at high risk for therapeutic failure. The objective of this retrospective cohort study was to determine predictors of early SCS explantation following device placement. Methods: The Medical Informatics Operating room Vitals and Events Repository database was queried for patients with a spinal cord stimulator and at least two years of follow-up (n = 56). A multivariate logistic regression was fitted. Recursive factor elimination with cross-validation and L1 penalization were used to reduce the number of predictors and minimize the risk of overfitting. The model was used to predict risk factors for explantation, odds ratio (OR), 95% confidence interval (CI), and false discovery rate-adjusted p-value. Results: The final model displayed adequate performance with an average precision of 0.769. Sleep disorders were identified as a statistically significant predictor of SCS explantation (OR: 3.88, CI: 1.36–11.04, FDR p-value: 0.0497). Conclusions: While further prospective studies are needed, our study indicates that sleep disorders are a risk factor for spinal cord stimulator explantation and should be considered during pre-operative evaluation.
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(This article belongs to the Section Pain Research)
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Open AccessSystematic Review
Advances in Genetic Risk Scores for Alzheimer’s Disease and Dementia: A Systematic Review
by
Stefanos N. Sampatakakis, Niki Mourtzi, Alex Hatzimanolis and Nikolaos Scarmeas
Neurol. Int. 2025, 17(7), 99; https://doi.org/10.3390/neurolint17070099 - 26 Jun 2025
Abstract
Background: Research concerning the genetic risk for dementia has recently been headed towards new directions. Novel findings from genome-wide association studies have highlighted the association of Alzheimer’s disease incidence with many gene polymorphisms, apart from the Apolipoprotein-E genotype. The identification of additional genetic
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Background: Research concerning the genetic risk for dementia has recently been headed towards new directions. Novel findings from genome-wide association studies have highlighted the association of Alzheimer’s disease incidence with many gene polymorphisms, apart from the Apolipoprotein-E genotype. The identification of additional genetic risk factors has led to the construction of specific genetic risk scores for dementia, considering many different genetic factors and specific biological pathways related to Alzheimer’s disease. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis method, summarizing existing data regarding genetic risk scores for Alzheimer’s disease and dementia, in order to improve the current understanding of the genetic underpinnings of dementia. In specific, five databases (PubMed/MEDLINE, Embase, Scopus, Web of science, and Cochrane Central) were searched using the keywords “genetic risk score”, “Alzheimer’s disease”, and “dementia” with specific inclusion and exclusion criteria. Results: From the 552 articles identified, we finally included 20 studies for the qualitative analysis. These reports were classified in three different categories of genetic scores: “polygenic risk scores (PRSs)” (including 11 studies), “pathway specific polygenic risk scores (p-PRSs)” (5 studies), and “complex genetic risk scores” (4 studies). Conclusions: Existing genetic risk scores have contributed to better dementia prediction and a better understanding of the underlying pathology. Novel approaches integrating multiple polygenic risk scores might ameliorate the accuracy of genetic risk scores. The combination of polygenic risk scores that are specific to related biological pathways or relevant biomarkers is of utmost importance to achieve a better predictive ability.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessReview
Advances in Diagnosis, Pathological Mechanisms, Clinical Impact, and Future Therapeutic Perspectives in Tay–Sachs Disease
by
María González-Sánchez, María Jesús Ramírez-Expósito and José Manuel Martínez-Martos
Neurol. Int. 2025, 17(7), 98; https://doi.org/10.3390/neurolint17070098 - 25 Jun 2025
Abstract
Tay–Sachs disease (TSD) is a rare and severe neurodegenerative disorder inherited in an autosomal recessive manner. It is caused by a deficiency of the enzyme hexosaminidase A, which is responsible for the degradation of GM2 gangliosides—lipids that accumulate in the nerve cells of
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Tay–Sachs disease (TSD) is a rare and severe neurodegenerative disorder inherited in an autosomal recessive manner. It is caused by a deficiency of the enzyme hexosaminidase A, which is responsible for the degradation of GM2 gangliosides—lipids that accumulate in the nerve cells of the central nervous system. The inability to break down these lipids leads to their progressive accumulation, resulting in irreversible brain damage. Mechanistically, TSD is caused by mutations in the HEXA gene, which encodes the alpha subunit of hexosaminidase A. These mutations disrupt enzyme activity and alter cellular pathways involved in lysosomal lipid degradation. Although Tay–Sachs specifically involves the alpha subunit, similar clinical features can be seen in Sandhoff disease, a related disorder caused by mutations in the HEXB gene, which encodes the beta subunit shared by hexosaminidase A and B. Tay–Sachs is classified into three clinical forms according to age of onset and symptom severity: the classic infantile form, which is the most common and severe; a juvenile (subacute) form; and an adult-onset form, which progresses more slowly and tends to present with milder symptoms. Diagnosis is based on enzymatic testing showing reduced or absent hexosaminidase A activity, confirmed by genetic testing. Prenatal diagnosis and genetic counseling play a key role in prevention and reproductive decision-making, especially in high-risk populations. Although no curative treatment currently exists, ongoing research is exploring gene therapy, enzyme replacement, and pharmacological approaches. Certain compounds, such as gemfibrozil, have shown potential to slow symptom progression. Early diagnosis and multidisciplinary care are essential to improving quality of life, although therapeutic options remain limited due to the progressive nature of the disease.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
A Retrospective Study of 10 Patients Exhibiting the “Pseudo Wartenberg Sign”
by
Lisa B. E. Shields, Vasudeva G. Iyer, Yi Ping Zhang and Christopher B. Shields
Neurol. Int. 2025, 17(7), 97; https://doi.org/10.3390/neurolint17070097 - 20 Jun 2025
Abstract
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Background/Objectives: The Wartenberg sign is a diagnostic feature of ulnar nerve neuropathy. It results from unbalanced activity of the abductor digiti minimi (ADM) and extensor digiti minimi (EDM) muscles secondary to weakness of the third palmar interosseous muscle. Rarely, this sign may occur
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Background/Objectives: The Wartenberg sign is a diagnostic feature of ulnar nerve neuropathy. It results from unbalanced activity of the abductor digiti minimi (ADM) and extensor digiti minimi (EDM) muscles secondary to weakness of the third palmar interosseous muscle. Rarely, this sign may occur in the absence of an underlying ulnar neuropathy, which we refer to as the “pseudo Wartenberg sign” (PWS). Methods: This is a retrospective review of 10 patients manifesting an inability to adduct the little finger towards the ring finger with no evidence of an ulnar neuropathy. We describe the clinical and electrodiagnostic (EDX) findings in these patients and discuss the pathophysiologic basis of PWS. Results: The most common cause was an injury in five (50.0%) patients: avulsion of the third volar interosseous muscle in two (20.0%), contracture of the ADM muscle in one (10.0%), and trauma-related dystonia in two (20.0%). The most frequent mechanism of PWS was focal dystonia of specific hand muscles in seven (70.0%) patients. Needle electromyography (EMG) demonstrated no denervation changes in ulnar nerve-innervated hand muscles; the motor and sensory conduction was normal in the ulnar nerve in all patients. Four (40.0%) patients underwent ultrasound studies, with a hyperechoic, avulsed third volar interosseous muscle in one, a hyperechoic and atrophic ADM muscle in one, normal hypothenar and extensor muscles in one, and a normal hypothenar muscle in one. Conclusions: Neurologists, neurosurgeons, and hand and orthopedic surgeons should be aware of the rare cases in which the inability to adduct the little finger may occur in the absence of ulnar neuropathy and look for other causes like avulsion of the third palmar interosseus muscle or focal hand dystonia.
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Open AccessArticle
Novel Gene-Informed Regional Brain Targets for Clinical Screening for Major Depression
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G. Lorenzo Odierna, Christopher F. Sharpley, Vicki Bitsika, Ian D. Evans and Kirstan A. Vessey
Neurol. Int. 2025, 17(6), 96; https://doi.org/10.3390/neurolint17060096 - 19 Jun 2025
Abstract
Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment
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Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment efficacy in MD is a substantial divergence in the mechanisms and brain networks involved in different subtypes of the disorder. The aim of this study was to identify novel brain regional targets for MD clinical screening using a gene-informed approach. Methods: A new analysis pipeline, called “Analysis Tool for Local Association of Neuronal Transcript Expression” (ATLANTE), was generated and validated. The pipeline identifies brain regions based on the shared high expression of user-generated gene lists; in this study, the pipeline was applied to discover brain regions that may be significant to MD. Results: Nine discrete brain regions of interest to MD were identified, including the temporal pole, anterior transverse temporal gyrus (Heschl’s gyrus), olfactory tubercle, ventral tegmental area, postcentral gyrus, CA1 of the hippocampus, olfactory area, perirhinal gyrus, and posterior insular cortex. The application of network and clustering analyses identified genes of special importance, including, most notably, PRKN. Conclusions: This study provides two major insights. The first is that several brain regions have unique MD-associated genetic architectures, indicating a potential explanation for subtype-specific dysfunction. The second insight is that the PRKN gene, which is strongly associated with Parkinson’s disease, is a key player amongst the MD-associated genes. These findings reveal novel targets for the clinical screening of depression and reinforce a mechanistic connection between MD and Parkinson’s disease.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
Two Decades of Huntington’s Disease in Varna, Bulgaria: A Retrospective Single-Centre Study of Clinical Trends and Challenges
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Mariya Levkova, Mihael Tsalta-Mladenov, Milena Stoyanova, Mari Hachmeriyan, Lyudmila Angelova and Ara Kaprelyan
Neurol. Int. 2025, 17(6), 95; https://doi.org/10.3390/neurolint17060095 - 18 Jun 2025
Abstract
Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present
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Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present clinical and genetic findings from a 20-year single-centre cohort. Methods: A retrospective review was conducted of patients evaluated for HD at the University Hospital “St. Marina” in Varna between 2004 and 2024. Data included demographics, CAG repeat length, clinical features, imaging, and psychiatric assessments. Statistical analysis focused on correlations between variables, with significance set at p < 0.05. Results: Out of 79 referred individuals, 43 were molecularly confirmed. The mean age of onset was 43 years, with a four-year diagnostic delay. The average CAG repeat length was 44.6, though two symptomatic patients had reduced penetrance alleles (38 and 39 repeats). Cognitive and psychiatric symptoms were each present in 72% of cases. Depression was significantly more prevalent in women (p = 0.011). Most patients had a positive family history, predominantly maternal. Conclusions: Our findings highlight diagnostic delays, gender-specific psychiatric vulnerabilities, and the importance of personalized care. Improved access to genetic counselling and early diagnosis are essential for optimizing outcomes.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessReview
Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions
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Dhruba Podder, Olivia Stala, Rahim Hirani, Adam M. Karp and Mill Etienne
Neurol. Int. 2025, 17(6), 94; https://doi.org/10.3390/neurolint17060094 - 18 Jun 2025
Abstract
Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in
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Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations.
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(This article belongs to the Section Pain Research)
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Open AccessArticle
Effects of Motor Preparation on Walking Ability in Active Ankle Dorsiflexion
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Hiroki Ito, Hideaki Yamaguchi, Ryosuke Yamauchi, Ken Kitai, Kazuhei Nishimoto and Takayuki Kodama
Neurol. Int. 2025, 17(6), 93; https://doi.org/10.3390/neurolint17060093 - 17 Jun 2025
Abstract
Background/Objectives: This study aimed to examine the influence of brain activity during motor preparation on walking ability, focusing on motor control during active ankle dorsiflexion. Methods: Participants were classified into high- and low-corticomuscular coherence (CMC), an index of neuromuscular control based on the
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Background/Objectives: This study aimed to examine the influence of brain activity during motor preparation on walking ability, focusing on motor control during active ankle dorsiflexion. Methods: Participants were classified into high- and low-corticomuscular coherence (CMC), an index of neuromuscular control based on the median value. Biomechanical and neurophysiological indices of active ankle dorsiflexion and walking ability were compared between the two groups. Additionally, a machine learning model was developed to accurately predict the CMC classification using brain neural activity during motor preparation. Results: The Cz-TA CMC (beta frequency band) during active ankle dorsiflexion successfully detected significant differences in the maximum dorsiflexion angle, inversion angular velocity, brain activity localization, and variations in Cz beta power values during the transition from motor preparation to execution. Furthermore, CMC identified significant differences in dorsiflexion angle changes after toe-off and inversion angles at initial contact during gait. A support-vector machine model predicting high or low CMC demonstrated high accuracy (Accuracy: 0.96, Precision: 0.92–1.00, Recall: 0.91–1.00, F1 Score: 0.95–0.96) during motor execution based on beta power values from −500 to 0 ms prior to the initiation of active ankle dorsiflexion (representing motor preparation). Conclusions: These findings highlight that the motor preparation processes of the brain during active ankle dorsiflexion are involved in walking ability and can be used to predict it. This indicator is independent of disease severity and holds the potential to provide a clinically versatile evaluation method.
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(This article belongs to the Topic Advances in Neurorehabilitation)
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Open AccessReview
Global Diseases Deserve Global Solutions: Alzheimer’s Disease
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Emma Twiss, Carley McPherson and Donald F. Weaver
Neurol. Int. 2025, 17(6), 92; https://doi.org/10.3390/neurolint17060092 - 14 Jun 2025
Abstract
Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by
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Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by the absence of cure therapies. Moreover, the risk factor relationship of dementia with rising global temperatures and air pollution further necessitates the urgency of a coordinated international response. With an extensive economic and emotional burden, AD is no longer just a disease; it is a worldwide societal crisis. This review presents five calls to action to address the AD global health emergency. First, AD research must be approached as an internationally performed activity, involving standardized data sharing, collaborative innovation, and improved access to pharmaceutical studies in low- and middle-income countries (LMICs), alongside increased diversity, inclusion, and equity in research. Second, there must be a commitment to develop universally accessible, affordable, and non-invasive diagnostic tools for AD. Third, advancements in AD therapeutics should prioritize the development of affordable agents, allowing for widespread geographic distribution. Fourth, we identify focus areas for global dementia risk reduction: sleep, head injury prevention, exercise, learning, and diet (SHIELD risk reduction strategy). Fifth, improving care for individuals with AD requires eliminating stigma through educational programs for both the public and caregivers. The escalating AD crisis demands an unprecedented global coalition in research, diagnostics, therapeutics, prevention, and education to avoid a future where the disease becomes the defining crisis of our era.
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(This article belongs to the Collection Brain Health Initiative: Advocacy in Global Neurology)
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Open AccessArticle
A Multimodal Multi-Stage Deep Learning Model for the Diagnosis of Alzheimer’s Disease Using EEG Measurements
by
Tuan Vo, Ali K. Ibrahim and Hanqi Zhuang
Neurol. Int. 2025, 17(6), 91; https://doi.org/10.3390/neurolint17060091 - 13 Jun 2025
Abstract
Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a
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Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a diagnostic tool for AD faces challenges due to its susceptibility to noise and the complexity involved in the analysis. Methods: This study introduces a novel methodology employing three distinct stages for data-driven AD diagnosis: signal pre-processing, frame-level classification, and subject-level classification. At the frame level, convolutional neural networks (CNNs) are employed to extract features from spectrograms, scalograms, and Hilbert spectra. These features undergo fusion and are then fed into another CNN for feature selection and subsequent frame-level classification. After each frame for a subject is classified, a procedure is devised to determine if the subject has AD or not. Results: The proposed model demonstrates commendable performance, achieving over 80% accuracy, 82.5% sensitivity, and 81.3% specificity in distinguishing AD patients from healthy individuals at the subject level. Conclusions: This performance enables early and accurate diagnosis with significant clinical implications, offering substantial benefits over the existing methods through reduced misdiagnosis rates and improved patient outcomes, potentially revolutionizing AD screening and diagnostic practices. However, the model’s efficacy diminishes when presented with data from frontotemporal dementia (FTD) patients, emphasizing the need for further model refinement to address the intricate nuances associated with the simultaneous detection of various neurodegenerative disorders alongside AD.
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(This article belongs to the Topic Translational Advances in Neurodegenerative Dementias, Second Edition)
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Open AccessCorrection
Correction: Latacz et al. Safety and Efficacy of Low-Dose Eptifibatide for Tandem Occlusions in Acute Ischemic Stroke. Neurol. Int. 2024, 16, 253–262
by
Paweł Latacz, Tadeusz Popiela, Paweł Brzegowy, Bartłomiej Lasocha, Krzysztof Kwiecień and Marian Simka
Neurol. Int. 2025, 17(6), 90; https://doi.org/10.3390/neurolint17060090 - 11 Jun 2025
Abstract
There was an error in the original publication [...]
Full article
Open AccessSystematic Review
Combined Transcranial Direct Current Stimulation and Functional Electrical Stimulation for Upper Limbs in Individuals with Stroke: A Systematic Review
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Alfredo Lerín-Calvo, Juan José Fernández-Pérez, Raúl Ferrer-Peña and Aitor Martín-Odriozola
Neurol. Int. 2025, 17(6), 89; https://doi.org/10.3390/neurolint17060089 - 9 Jun 2025
Abstract
Background: Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are established interventions to enhance upper limb motor function (ULMF) in people with stroke (PwS). However, evidence supporting their combined use remains limited and inconsistent. This systematic review aims to evaluate the
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Background: Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are established interventions to enhance upper limb motor function (ULMF) in people with stroke (PwS). However, evidence supporting their combined use remains limited and inconsistent. This systematic review aims to evaluate the effectiveness of combined tDCS and FES for improving ULMF, activity, and participation in PwS. Methods: A systematic search was conducted across MEDLINE, CINAHL, SPORTDiscus, CENTRAL, SCOPUS, and Web of Science from inception to December 2024. Randomized and controlled clinical trials (RCTs) involving adults (≥18 years) with acute, subacute, or chronic stroke undergoing combined tDCS and FES interventions were included. Methodological quality was assessed with the PEDro scale, and risk of bias was evaluated using the Cochrane RoB2 tool. A qualitative synthesis was performed employing a five-level evidence grading system. Results: Five RCTs involving 148 participants (mean age range: 50.6–61.2 years; 26% female) were included. Stroke chronicity ranged from 7.6 days to 27.5 months post-onset. Four studies reported significant ULMF improvements with the combined intervention. However, activity and participation outcomes were inconsistently assessed, and results remained inconclusive. Methodological quality varied, with one study rated as excellent, two as good, one as fair, and one as poor. The risk of bias was rated high or with concerns in four out of five studies. Conclusions: Based on qualitative synthesis, moderate-level evidence supports the combined use of tDCS and FES for improving ULMF in PwS. However, high variability in protocols, small sample sizes, and the increased risk of bias in most studies limit the strength of these conclusions. Standardized protocols and larger high-quality RCTs are needed to confirm the effectiveness of this combined intervention.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessCommunication
Fatigue and Its Association with Upper Limb Function in People with Multiple Sclerosis
by
Erica Grange, Davide Marengo, Rachele Di Giovanni, Giampaolo Brichetto, Margit Mueller, Andrea Tacchino, Rita Bertoni, Francesco Zagari, Angelo Pappalardo, Luca Prosperini, Rosalba Rosato, Davide Cattaneo and Claudio Solaro
Neurol. Int. 2025, 17(6), 88; https://doi.org/10.3390/neurolint17060088 - 9 Jun 2025
Abstract
Background and Objectives: This cross-sectional study investigates the association between fatigue and upper limb (UL) function in people with Multiple Sclerosis (PwMS). Methods: Adult PwMS were recruited from five Italian MS centers. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), while
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Background and Objectives: This cross-sectional study investigates the association between fatigue and upper limb (UL) function in people with Multiple Sclerosis (PwMS). Methods: Adult PwMS were recruited from five Italian MS centers. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), while UL function was assessed through the Box and Block Test (BBT), Nine-Hole Peg Test (9HPT), and Hand-Grip Strength (HGS). Data analysis included Spearman rank correlations and Mann–Whitney U tests. Results: A total of 261 participants were involved. Significant correlations were found between fatigue severity, UL function, and patient-reported manual ability. Physical and cognitive aspects of fatigue were independently related to functional impairments. Participants with clinically relevant fatigue demonstrated lower subjective UL function, poorer BBT and HGS performance, and greater HGS asymmetry. Discussion: The study underscores the complex relationship between fatigue and functional impairments in MS. The findings suggest both strength and dexterity contribute to the perception of clinically relevant fatigue in PwMS, highlighting the importance of incorporating both domains to complement neurological assessment. Conclusion: Fatigue in PwMS is linked to both subjective and objective measures of UL function. Assessing strength and dexterity alongside fatigue may enhance clinical understanding and inform targeted rehabilitation strategies.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
The C/C Genotype of the C-1019G (rs6295) Polymorphism of the 5-HT1A Receptor Gene Is Associated with Lower Susceptibility to Depressive Symptoms in a Rural Population in Mexico
by
Margarita Hernandez-Mixteco, Olga Lidia Valenzuela, Cecilia Luz Balderas-Vazquez, Paola Castillo-Juárez, Sandra Rivera-Gutiérrez, Rocío Liliana García-Reyes, Gilberto Cornejo-Estudillo, Ricardo Jiovanni Soria-Herrera, Moises León-Juárez, Addy Cecilia Helguera-Repetto, Daniel Valencia-Trujillo, Victoria Campos-Peña, Eliud Alfredo Garcia-Montalvo and Jorge Francisco Cerna-Cortés
Neurol. Int. 2025, 17(6), 87; https://doi.org/10.3390/neurolint17060087 - 31 May 2025
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Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3%
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Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico.
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Open AccessCase Report
Idiopathic Normal-Pressure Hydrocephalus Revealed by Systemic Infection: Clinical Observations of Two Cases
by
Shinya Watanabe, Yasushi Shibata, Kosuke Baba, Yuhei Kuriyama and Eiichi Ishikawa
Neurol. Int. 2025, 17(6), 86; https://doi.org/10.3390/neurolint17060086 - 30 May 2025
Abstract
Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in
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Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients.
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(This article belongs to the Section Brain Tumor and Brain Injury)
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Open AccessArticle
Gender Differences in Obstructive Sleep Apnea: A Preliminary Clinical and Polysomnographic Investigation
by
Alessandra Castelnuovo, Sara Marelli, Salvatore Mazzeo, Francesca Casoni, Paola Proserpio, Alessandro Oldani, Alessandro Bombaci, Elisa Bortolin, Giulia Bruschi, Federica Agosta, Massimo Filippi, Luigi Ferini-Strambi and Maria Salsone
Neurol. Int. 2025, 17(6), 85; https://doi.org/10.3390/neurolint17060085 - 29 May 2025
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Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown.
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Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown. This study aimed to investigate the neuropsychological and polysomnographic (PSG) differences between OSA females and males in order to detect the impact of gender on clinical manifestation and PSG features. Methods: Data were collected from 28 OSA patients (14 females and 14 males matched for age, education, and disease severity). All patients performed a complete neuropsychological evaluation, Epworth sleepiness scale, and whole-night PSG. To evaluate the relationship between specific sleep profiles and cognitive performance, PSG parameters were correlated to scores obtained on neuropsychological tests. Results: Both male and female groups performed within the normal range across all administered neuropsychological tests, according to Italian normative values. Compared with OSA males, female patients showed significantly lower values on the Rey–Osterrieth Complex Figure (ROCF) Recall Test. By contrast, no significant statistical clinical difference emerged between the two OSA groups in terms of clinical manifestation and sleep parameters. Conclusions: This study improves the knowledge on gender-related cognitive impairment in OSA patients. Our preliminary findings demonstrate that the ROCF Recall Test may be altered in OSA females, but not in males. Further longitudinal studies are needed to investigate whether OSA female patients will develop a frank dementia over time.
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Open AccessArticle
Treatment-Associated Neuroplastic Changes in People with Stroke-Associated Ataxia—An fMRI Study
by
Patricia Meier, Christian Siedentopf, Lukas Mayer-Suess, Michael Knoflach, Stefan Kiechl, Gudrun Sylvest Schönherr, Astrid E. Grams, Elke R. Gizewski, Claudia Lamina, Malik Galijasevic and Ruth Steiger
Neurol. Int. 2025, 17(6), 84; https://doi.org/10.3390/neurolint17060084 - 29 May 2025
Abstract
Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke
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Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke patients with ataxic symptoms, to follow up on changes in motor function and balance due to recovery and rehabilitation, and to investigate the different effects of two treatment methods on neuronal plasticity. Methods: Therefore, fMRI-paradigms foot tapping and the motor imagery (MI) of a balancing task (tandem walking) were employed. Results: The paradigms investigated were suitable for ataxic stroke patients to monitor changes in neuroplasticity while revealing increased activity in the primary motor cortex (M1) and the cerebellum over 3 months of treatment. Furthermore, analysis of the more complex balance task revealed augmented activation of association areas due to training. Coordination exercises, constituting a specific treatment of ataxic symptoms, indicate more consolidated brain activations, corresponding to a faster motor learning process. Activation within Brodmann Area 7 has been prominent among all paradigms, indicating a special importance of this region for coordinative functions. Conclusions: Further studies are needed to confirm our results in larger patient groups. Clinical Trial Registration: German Clinical Trials Registry (drks.de). Identifier: DRKS00020825. Registered 16.07.2020.
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(This article belongs to the Topic Advances in Exercise-Induced Neurogenesis, Neuronal and Functional Adaptations in Neurorehabilitation)
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