Neurology International

21 pages, 439 KiB

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 (registering DOI) - 15 Jul 2025

Abstract

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

14 pages, 879 KiB

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)

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17 pages, 2942 KiB

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

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

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8 pages, 721 KiB

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)

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13 pages, 256 KiB

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)

13 pages, 664 KiB

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)

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12 pages, 274 KiB

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 [...] Read more.

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

11 pages, 693 KiB

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 [...] Read more.

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. Full article

(This article belongs to the Section Pain Research)

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14 pages, 668 KiB

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 [...] Read more.

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. Full article

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

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Graphical abstract

26 pages, 1551 KiB

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 [...] Read more.

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. Full article

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

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11 pages, 2307 KiB

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

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 [...] Read more.

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. Full article

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24 pages, 4371 KiB

Open AccessArticle

Novel Gene-Informed Regional Brain Targets for Clinical Screening for Major Depression

by 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 [...] Read more.

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. Full article

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

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9 pages, 616 KiB

Open AccessArticle

Two Decades of Huntington’s Disease in Varna, Bulgaria: A Retrospective Single-Centre Study of Clinical Trends and Challenges

by 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 [...] Read more.

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. Full article

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

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30 pages, 555 KiB

Open AccessReview

Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions

by 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 [...] Read more.

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. Full article

(This article belongs to the Section Pain Research)

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17 pages, 1429 KiB

Open AccessArticle

Effects of Motor Preparation on Walking Ability in Active Ankle Dorsiflexion

by 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 [...] Read more.

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. Full article

(This article belongs to the Topic Advances in Neurorehabilitation)

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20 pages, 1278 KiB

Open AccessReview

Global Diseases Deserve Global Solutions: Alzheimer’s Disease

by 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 [...] Read more.

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. Full article

(This article belongs to the Collection Brain Health Initiative: Advocacy in Global Neurology)

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21 pages, 1561 KiB

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 [...] Read more.

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. Full article

(This article belongs to the Topic Translational Advances in Neurodegenerative Dementias, Second Edition)

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1 pages, 157 KiB

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

17 pages, 782 KiB

Open AccessSystematic Review

Combined Transcranial Direct Current Stimulation and Functional Electrical Stimulation for Upper Limbs in Individuals with Stroke: A Systematic Review

by 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 [...] Read more.

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. Full article

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

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