Neurology International

16 pages, 955 KB

Open AccessReview

Deep Brain Stimulation: Psychological and Neuroethical Perspectives

by Stella Sremic, Antea Krsek and Lara Baticic

Neurol. Int. 2025, 17(10), 158; https://doi.org/10.3390/neurolint17100158 - 2 Oct 2025

Deep brain stimulation (DBS) is an evolving neurosurgical treatment, originally developed for movement disorders such as Parkinson’s disease, essential tremor, and dystonia. In recent years, it has been increasingly applied to psychiatric and cognitive disorders. This review aimed to summarize the psychological and [...] Read more.

Deep brain stimulation (DBS) is an evolving neurosurgical treatment, originally developed for movement disorders such as Parkinson’s disease, essential tremor, and dystonia. In recent years, it has been increasingly applied to psychiatric and cognitive disorders. This review aimed to summarize the psychological and neuroethical dimensions of DBS, with particular attention to cognitive, emotional, and personality-related outcomes. While DBS can significantly enhance quality of life, it may also lead to subtle or overt changes in cognition, affect, and self-perception, especially in patients with neuropsychiatric comorbidities. Comprehensive psychological evaluation, both pre- and post-operatively, is essential. Findings from recent trials highlight a balance of potential risks and benefits that must be communicated transparently to patients. From a neuroethical perspective, DBS raises important questions regarding personal identity and autonomy, concerns that will become increasingly relevant as the technology advances. This paper underscores the need for more systematic research and the development of personalized care protocols that address not only motor outcomes but also psychosocial well-being. Full article

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

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14 pages, 673 KB

Open AccessReview

Is Vitamin B6 a Precision Therapy for Neonatal Seizures?

by Raffaele Falsaperla, Vincenzo Sortino, Bruna Scalia and Marco Andrea Nicola Saporito

Neurol. Int. 2025, 17(10), 157; https://doi.org/10.3390/neurolint17100157 - 1 Oct 2025

Abstract

Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision [...] Read more.

Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision therapy in neonatal seizure syndromes, particularly in pyridoxine-responsive conditions. Methods: We conducted a narrative review of the biochemical functions of vitamin B6, focusing on its active form, pyridoxal 5′-phosphate (PLP), and its role as a coenzyme in neurotransmitter synthesis. We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings. Results: Vitamin B6 is essential for the synthesis of gamma-aminobutyric acid (GABA), dopamine, and serotonin, with PLP-dependent enzymes such as glutamic acid decarboxylase and aromatic L-amino acid decarboxylase playing central roles. Deficiencies in PLP due to genetic mutations or metabolic disruptions can result in treatment-resistant neonatal seizures. Early supplementation, especially in suspected vitamin B6-dependent epilepsies, may provide both diagnostic clarity and seizure control, potentially reducing exposure to conventional antiseizure medications. Conclusions: Vitamin B6-responsive epilepsies highlight the clinical value of mechanism-based, individualized treatment approaches in neonatology. Incorporating genetic and metabolic screening into seizure management may improve outcomes and aligns with the principles of precision medicine. Full article

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

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15 pages, 2924 KB

Open AccessSystematic Review

The Neuroanatomical Correlates of Urine Storage: An Activation Likelihood Estimation Meta-Analysis of Functional Neuroimaging Studies

by Christoph Müller and Albert Kaufmann

Neurol. Int. 2025, 17(10), 156; https://doi.org/10.3390/neurolint17100156 - 30 Sep 2025

Abstract

Background: Urinary continence is based on a complex interplay between urine storage and voiding involving both spinal reflex circuits and supraspinal brain areas to coordinate voluntary control over emptying. Despite a vast number of studies on the pathophysiology of neurogenic bladder and urge [...] Read more.

Background: Urinary continence is based on a complex interplay between urine storage and voiding involving both spinal reflex circuits and supraspinal brain areas to coordinate voluntary control over emptying. Despite a vast number of studies on the pathophysiology of neurogenic bladder and urge incontinence, less is known about the central correlates of urine storage. Methods: An ALE (activation likelihood estimation) meta-analysis including a total count of 14 studies investigating 243 participants under different conditions of bladder filling during functional neuroimaging was performed to demonstrate the neuroanatomical correlates of urine storage. The literature search and reporting were conducted according to the PRISMA-P 2020 guideline. Data analysis was performed using the GingerAle software version 3.0.2 and was displayed with the Mango software 4.1 on an anatomical MNI template. Results: Synthesizing studies on the functional neuroanatomy of urine storage, bihemispheric clusters of activation in the thalamus, the insula and the cingulate were observed. Conclusion: The present ALE meta-analysis indicates that the supraspinal representation of urine storage involves areas of autonomous–homeostatic processing which allow for the perception of the usually unconscious inner state of bladder filling and enable postponing and voluntary voiding. Full article

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14 pages, 471 KB

Open AccessSystematic Review

Gut Microbiota, Mild Cognitive Impairment and Dementia: A Systematic Review

by Claudio Tana, Samanta Moffa, Marco Tana, Claudio Ucciferri and Livia Moffa

Neurol. Int. 2025, 17(10), 155; https://doi.org/10.3390/neurolint17100155 - 28 Sep 2025

Abstract

Background: Alterations of the gut microbiota have been increasingly implicated in the pathogenesis of dementia through mechanisms involving systemic inflammation, immune dysregulation, and gut–brain axis disruption. Clinical evidence, however, remains fragmented. Objectives: This systematic review aimed to characterize gut microbiota profiles in individuals [...] Read more.

Background: Alterations of the gut microbiota have been increasingly implicated in the pathogenesis of dementia through mechanisms involving systemic inflammation, immune dysregulation, and gut–brain axis disruption. Clinical evidence, however, remains fragmented. Objectives: This systematic review aimed to characterize gut microbiota profiles in individuals with mild cognitive impairment (MCI) or Alzheimer’s dementia (AD), explore mechanistic associations with neurodegeneration, and evaluate the impact of microbiota-targeted interventions on cognitive outcomes. Methods: Following PRISMA 2020 guidelines and a registered protocol (PROSPERO CRD420251074832), PubMed/Medline was searched through May 2025. Eligible studies included randomized controlled trials (RCTs) and cohort and case–control studies assessing microbiota composition or interventions in participants with MCI or AD. Results: Twenty-one studies were included (1 RCT, 20 observational; sample size 22–302). Most used 16S rRNA sequencing; one used shotgun metagenomics. Across cohorts, MCI and AD patients consistently showed reduced short-chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcaceae, Lachnospiraceae) and increased pro-inflammatory taxa (Escherichia/Shigella, Enterobacteriaceae, Bacteroides). Several studies reported reduced microbial diversity. Specific taxa, including Akkermansia muciniphila and Faecalibacterium, were associated with amyloid burden, hippocampal atrophy, and cognitive decline. Environmental and dietary factors influenced microbial composition and cognition. The RCT reported that probiotic supplementation improved inflammatory markers and BDNF levels, although changes in microbiota composition were inconsistent. Conclusions: Gut dysbiosis is strongly associated with cognitive impairment and markers of neurodegeneration. Modulation of the microbiota through diet and probiotics emerges as a promising avenue for dementia prevention and management, though robust longitudinal and interventional studies are needed to confirm causality and therapeutic efficacy. Full article

(This article belongs to the Section Aging Neuroscience)

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18 pages, 1342 KB

Open AccessArticle

Fractional Anisotropy Alterations in Key White Matter Pathways Associated with Cognitive Performance Assessed by MoCA

by Nauris Zdanovskis, Kalvis Kaļva, Ardis Platkājis, Andrejs Kostiks, Kristīne Šneidere, Guntis Karelis and Ainārs Stepens

Neurol. Int. 2025, 17(10), 154; https://doi.org/10.3390/neurolint17100154 - 25 Sep 2025

Abstract

Objectives: This study investigated fractional anisotropy (FA) differences within key white matter tracts across patient groups stratified by Montreal Cognitive Assessment (MoCA) scores, aiming to evaluate FA’s potential as a biomarker for cognitive impairment. Methods: Seventy participants (aged 57–96 years) were categorized into [...] Read more.

Objectives: This study investigated fractional anisotropy (FA) differences within key white matter tracts across patient groups stratified by Montreal Cognitive Assessment (MoCA) scores, aiming to evaluate FA’s potential as a biomarker for cognitive impairment. Methods: Seventy participants (aged 57–96 years) were categorized into high (HP, MoCA ≥ 26), moderate (MP, MoCA 18–25), and low (LP, MoCA < 18) cognitive performance groups. Diffusion Tensor Imaging (DTI) was used to obtain FA values in corticospinal tracts, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum. Statistical analyses included ANOVA and post-hoc tests. Results: Significant differences in FA values and normative percentiles were observed across cognitive groups in several tracts. Notably, the MP group exhibited significantly higher FA values in the Left Superior Longitudinal Fasciculus—Arcuate (mean FA 0.329 vs. LP 0.306, p = 0.033) and Right Superior Longitudinal Fasciculus—Arcuate (mean FA 0.329 vs. LP 0.306, p = 0.009), Left Inferior Fronto-Occipital Fasciculus (mean FA 0.308 vs. LP 0.283, p = 0.021), and Right Inferior Fronto-Occipital Fasciculus (mean FA 0.289 vs. LP 0.266, p = 0.017) compared to the LP group. Conclusions: Our findings reveal significant FA alterations across MoCA-defined cognitive groups, with moderate impairment showing higher FA than low performance. This suggests FA may reflect complex microstructural changes in early cognitive decline. While our modest sample size, particularly in the low-performance group, limits definitive conclusions, these results highlight the need for larger, multimodal studies to validate FA’s role as a sensitive, albeit complex, biomarker for cognitive impairment. Full article

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

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23 pages, 366 KB

Open AccessReview

Impact of Gut–Brain Axis and Probiotics on Alzheimer’s Disease

by Raghad Tabaza and Richard E. Hartman

Neurol. Int. 2025, 17(10), 153; https://doi.org/10.3390/neurolint17100153 - 24 Sep 2025

Abstract

This review explores links between the gut–brain axis, probiotics, and Alzheimer’s disease (AD). Using PRISMA-aligned methods, we examined literature from PubMed, ClinicalTrials.gov, and Google Scholar. Studies show that probiotics may reduce AD symptoms by modulating neuroinflammation, microbial composition, and neurotransmitter signaling. Probiotic strains [...] Read more.

This review explores links between the gut–brain axis, probiotics, and Alzheimer’s disease (AD). Using PRISMA-aligned methods, we examined literature from PubMed, ClinicalTrials.gov, and Google Scholar. Studies show that probiotics may reduce AD symptoms by modulating neuroinflammation, microbial composition, and neurotransmitter signaling. Probiotic strains such as B. breve and L. plantarum were found to be beneficial in early AD or mild cognitive impairment. Limitations include short intervention periods and strain variability. Clinical guidelines and research recommendations are discussed. Mechanisms involve immune signaling, neurotransmitter synthesis (GABA and serotonin), and modulation of systemic inflammation. Full article

(This article belongs to the Collection Advances in Neurodegenerative Diseases)

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15 pages, 1648 KB

Open AccessArticle

The Concomitant Effect of the Antiepileptic Drug Lacosamide and rTMS on an SH-SY5Y Model of Neuronal Excitability

by Ioannis Dardalas, Efstratios K. Kosmidis, Vasilios K. Kimiskidis, Roza Lagoudaki, Theodoros Samaras, Theodoros Moysiadis, Dimitrios Kouvelas and Chryssa Pourzitaki

Neurol. Int. 2025, 17(10), 152; https://doi.org/10.3390/neurolint17100152 - 24 Sep 2025

Abstract

Background/Objectives: Epilepsy is identified by irregular neuronal hyperexcitability, generating recurrent seizures. Despite many available pharmacological treatments, certain patients with drug-resistant epilepsy may require novel therapeutic approaches. In the present study, we aimed to evaluate the effects of lacosamide, low-frequency repetitive transcranial magnetic [...] Read more.

Background/Objectives: Epilepsy is identified by irregular neuronal hyperexcitability, generating recurrent seizures. Despite many available pharmacological treatments, certain patients with drug-resistant epilepsy may require novel therapeutic approaches. In the present study, we aimed to evaluate the effects of lacosamide, low-frequency repetitive transcranial magnetic stimulation, and their combination on intracellular calcium dynamics in an in vitro model of neuronal excitability, hypothesizing that these interventions could mitigate potassium chloride-induced neuronal excitation. Methods: We utilized differentiated SH-SY5Y human neuroblastoma cells as an in vitro model of neuronal excitability. Neuronal excitability was induced with 50 mM KCl, and cells were treated with lacosamide (300 µM), rTMS (1 Hz), or their combination. Intracellular calcium levels were quantified using fluo-4 AM fluorescence calcium imaging, with changes expressed as percentage change in fluorescence intensity (%ΔF/F) relative to baseline. Results: The combination of lacosamide and rTMS was the most effective, significantly reducing KCl-induced calcium elevation (ΔF/F = 9.15) compared to lacosamide alone (ΔF/F = 17.11), rTMS alone (ΔF/F = 23.70), and the untreated cells serving as controls (ΔF/F = 66.70). The combination showed a statistically significant effect, with enhanced suppression of neuronal excitability compared to individual treatments. Conclusions: Lacosamide and low-frequency rTMS (1 Hz) effectively attenuated KCl-induced changes in intracellular calcium levels in vitro, with their combination demonstrating the highest efficacy. These findings suggest a promising foundation in the management of drug-resistant epilepsy. Future studies are necessitated to validate these results and benefit clinical translation. Full article

(This article belongs to the Special Issue Molecular Research of CNS Diseases and Neurological Disorders)

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26 pages, 3649 KB

Open AccessArticle

SeruNet-MS: A Two-Stage Interpretable Framework for Multiple Sclerosis Risk Prediction with SHAP-Based Explainability

by Serra Aksoy, Pinar Demircioglu and Ismail Bogrekci

Neurol. Int. 2025, 17(9), 151; https://doi.org/10.3390/neurolint17090151 - 22 Sep 2025

Abstract

Background/Objectives: Multiple sclerosis (MS) is a chronic demyelinating disease where early identification of patients at risk of conversion from clinically isolated syndrome (CIS) to clinically definite MS remains a critical unmet clinical need. Existing machine learning approaches often lack interpretability, limiting clinical trust [...] Read more.

Background/Objectives: Multiple sclerosis (MS) is a chronic demyelinating disease where early identification of patients at risk of conversion from clinically isolated syndrome (CIS) to clinically definite MS remains a critical unmet clinical need. Existing machine learning approaches often lack interpretability, limiting clinical trust and adoption. The objective of this research was to develop a novel two-stage machine learning framework with comprehensive explainability to predict CIS-to-MS conversion while addressing demographic bias and interpretability limitations. Methods: A cohort of 177 CIS patients from the National Institute of Neurology and Neurosurgery in Mexico City was analyzed using SeruNet-MS, a two-stage framework that separates demographic baseline risk from clinical risk modification. Stage 1 applied logistic regression to demographic features, while Stage 2 incorporated 25 clinical and symptom features, including MRI lesions, cerebrospinal fluid biomarkers, electrophysiological tests, and symptom characteristics. Patient-level interpretability was achieved through SHAP (SHapley Additive exPlanations) analysis, providing transparent attribution of each factor’s contribution to risk assessment. Results: The two-stage model achieved a ROC-AUC of 0.909, accuracy of 0.806, precision of 0.842, and recall of 0.800, outperforming baseline machine learning methods. Cross-validation confirmed stable performance (0.838 ± 0.095 AUC) with appropriate generalization. SHAP analysis identified periventricular lesions, oligoclonal bands, and symptom complexity as the strongest predictors, with clinical examples illustrating transparent patient-specific risk communication. Conclusions: The two-stage approach effectively mitigates demographic bias by separating non-modifiable factors from actionable clinical findings. SHAP explanations provide clinicians with clear, individualized insights into prediction drivers, enhancing trust and supporting decision making. This framework demonstrates that high predictive performance can be achieved without sacrificing interpretability, representing a significant step forward for explainable AI in MS risk stratification and real-world clinical adoption. Full article

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

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10 pages, 237 KB

Open AccessArticle

Effect of Hypothyroidism on the Risk of Carpal Tunnel Syndrome and Electrodiagnostic Parameters

by Ahmad R. Abuzinadah

Neurol. Int. 2025, 17(9), 150; https://doi.org/10.3390/neurolint17090150 - 18 Sep 2025

Abstract

Background: Hypothyroidism has been implicated as a risk factor for carpal tunnel syndrome (CTS). However, the effect of hypothyroidism on the risk of CTS has not been studied in large, non-selective clinic populations, and the impact of hypothyroidism on electrodiagnostic parameters remains inadequately [...] Read more.

Background: Hypothyroidism has been implicated as a risk factor for carpal tunnel syndrome (CTS). However, the effect of hypothyroidism on the risk of CTS has not been studied in large, non-selective clinic populations, and the impact of hypothyroidism on electrodiagnostic parameters remains inadequately understood. Methods: In this retrospective study, we examined 480 patients referred for upper limb electrodiagnostic evaluation. We compared the prevalence of CTS among patients with and without hypothyroidism, adjusting for age and gender. Additionally, we compared the median nerve sensory and motor latencies and comparative latency studies (COLS) [median-to-ulnar comparison through palmar difference (Palmdiff) and ring difference studies (Ringdiff); and median-to-radial comparison through a thumb difference study (Thumbdiff)] among patients with and without hypothyroidism disease, stratified by CTS status and age groups. Results: The crude prevalence of CTS was higher among patients with hypothyroidism (79.7%) compared to those without (61.8%) (p = 0.005). However, after adjusting for age and gender, logistic regression analysis revealed a non-significant association between hypothyroidism and CTS (adjusted odds ratio (OR): 1.71; 95% CI: 0.89–3.28, p = 0.106). CTS was more prevalent among patients with hypothyroidism under 50 years of age (OR: 2.59; 95% CI: 1.17–5.73, p = 0.018). There were no significant differences in any electrodiagnostic parameters between patients with and without hypothyroidism among CTS and non-CTS groups. Conclusions: Hypothyroidism increased the risk of CTS among patients under 50 years of age. The electrodiagnostic parameters used for CTS diagnosis were not influenced by the presence of hypothyroidism. Full article

(This article belongs to the Section Pain Research)

17 pages, 699 KB

Open AccessReview

Neurovascular Pathophysiology and Emerging Biomarkers in Cerebral Malaria: An Integrative Perspective

by Damian Pikor, Mikołaj Hurła, Natalia Banaszek-Hurła, Alicja Drelichowska and Małgorzata Paul

Neurol. Int. 2025, 17(9), 149; https://doi.org/10.3390/neurolint17090149 - 15 Sep 2025

Cited by 1

Abstract

Cerebral malaria is a life-threatening neurological complication of Plasmodium falciparum infection and a leading cause of pediatric mortality in endemic regions of sub-Saharan Africa. It is defined clinically by coma accompanied by peripheral parasitemia, without alternative causes. Pathogenetically, cytoadherence of parasitized erythrocytes in [...] Read more.

Cerebral malaria is a life-threatening neurological complication of Plasmodium falciparum infection and a leading cause of pediatric mortality in endemic regions of sub-Saharan Africa. It is defined clinically by coma accompanied by peripheral parasitemia, without alternative causes. Pathogenetically, cytoadherence of parasitized erythrocytes in the cerebral microvasculature, together with a widespread inflammatory response and endothelial activation, causes profound microvascular injury. This injury includes disruption of the blood–brain barrier and the development of multifactorial cerebral oedema (both vasogenic and cytotoxic), resulting in elevated intracranial pressure and often diffuse brain swelling as seen on imaging in fatal cases. Recent high-resolution MRI studies in pediatric cohorts from these endemic regions have identified characteristic neuroimaging findings such as basal ganglia infarcts, brainstem lesions, and corpus callosum abnormalities that strongly predict poor outcomes. Notably, circulating extracellular vesicles—released by parasitized erythrocytes and activated endothelial cells have emerged as potent mediators of microvascular inflammation. Extracellular vesicles contain parasite-derived antigens and host inflammatory signals, implicating them in disease mechanisms. These vesicles are under investigation as novel diagnostic and prognostic biomarkers for severe malaria. Importantly, survivors of cerebral malaria often endure persistent neurocognitive impairments, behavioral problems, and epilepsy, underscoring the need to prevent secondary neuronal injury during the acute phase to reduce long-term disability. Taken together, these insights highlight the interplay between cerebral microvascular pathology and neurological outcome in cerebral malaria. This review synthesizes recent advances in the pathophysiology of cerebral malaria and cutting-edge diagnostic modalities. It highlights novel therapeutic targets and neuroprotective strategies that may enable precision medicine approaches aimed at preventing lasting neurological disability in survivors. Full article

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

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12 pages, 1562 KB

Open AccessArticle

Association Between Carotid Artery Small Plaque on Computed Tomography Angiography and Embolic Stroke of Undetermined Source

by Junpei Nagasawa, Tatsuhiro Yokoyama, Makiko Ogawa, Ryuichi Okamoto, Mari Shibukawa, Junya Ebina, Takehisa Hirayama and Osamu Kano

Neurol. Int. 2025, 17(9), 148; https://doi.org/10.3390/neurolint17090148 - 14 Sep 2025

Abstract

Objectives: While traditionally, carotid plaques with significant stenosis have been considered major embolic sources, recent evidence suggests that even non-stenotic small plaques with a <50% stenosis rate may contribute to cerebral infarction. Herein, we evaluated the relationship between non-stenotic small plaques and [...] Read more.

Objectives: While traditionally, carotid plaques with significant stenosis have been considered major embolic sources, recent evidence suggests that even non-stenotic small plaques with a <50% stenosis rate may contribute to cerebral infarction. Herein, we evaluated the relationship between non-stenotic small plaques and embolic stroke of undetermined source (ESUS) using computed tomography angiography (CTA). Materials and Methods: We retrospectively reviewed our single-institutional database of hospitalized patients with stroke between April 2017 and December 2022 and enrolled them with ESUS. We evaluated the presence or absence of non-stenotic carotid artery plaque lesions ipsilateral and contralateral to the cerebral infarction lesion using CTA. A neurologist, blinded to the stroke side and all other clinical information, reviewed each CTA and viewed the axial and sagittal CTA source images. In each image, a line perpendicular to the vessel wall was drawn and the plaque diameter was measured. The largest part was considered as the maximum plaque diameter. Results: A total of 951 patients with stroke were hospitalized during the study period. Among these, 35 patients with unilateral anterior circulation ESUS were enrolled. Plaque prevalence > 3 mm was compared between the carotid artery on the ESUS side and contralateral carotid artery. The prevalences were 31% and 8% on the ESUS and contralateral sides, respectively. Plaques > 3 mm were often found on the ESUS side. Conclusions: Patients with ESUS were more likely to exhibit non-stenotic plaques of ≥3 mm in the infarcted carotid artery than in the contralateral carotid artery. Thus, small non-stenotic plaques may be the embolization source in ESUS, and CT angiography is useful for these evaluations. Full article

(This article belongs to the Special Issue Towards an All-Inclusive Paradigm for Acute Stroke Treatment—Challenges and Innovations)

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15 pages, 493 KB

Open AccessArticle

A Pilot Study: The Effect of CPAP Intervention on Sleep Architecture and Cognition in Alzheimer’s Disease Patients with Obstructive Sleep Apnea

by Carmen L. Frias, Marta Almeria, Judith Castejon, Cristina Artero, Giovanni Caruana, Andrea Elias-Mas, Karol Uscamaita, Virginia Hawkins, Nicola J. Ray, Mariateresa Buongiorno, Natalia Cullell and Jerzy Krupinski

Neurol. Int. 2025, 17(9), 147; https://doi.org/10.3390/neurolint17090147 - 11 Sep 2025

Abstract

Background: Obstructive sleep apnea (OSA) is highly prevalent in the early stages of Alzheimer’s disease (AD), and its hallmark, sleep fragmentation, may accelerate cognitive decline. Continuous positive airway pressure (CPAP) improves OSA-related hypoxia during slow-wave sleep, but its cognitive benefits in AD remain [...] Read more.

Background: Obstructive sleep apnea (OSA) is highly prevalent in the early stages of Alzheimer’s disease (AD), and its hallmark, sleep fragmentation, may accelerate cognitive decline. Continuous positive airway pressure (CPAP) improves OSA-related hypoxia during slow-wave sleep, but its cognitive benefits in AD remain unclear. Methods: We performed a 12-month sub-analysis of a prospective, longitudinal pilot study that enrolled 21 adults (median age = 77 yr; 71% women) with Mild Cognitive Impairment (MCI) with AD confirmed biomarkers and polysomnography-diagnosed OSA. All participants underwent baseline overnight polysomnography (PSG) and neuropsychological testing (Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) that were repeated after 12 months. Twelve participants were CPAP-compliant (moderate/severe OSA) and nine were non-users (mild OSA/intolerance). Cognitive change scores (Δ = 12 months -baseline) were compared with Generalized Linear Models (GLM) adjusted for baseline cognition and Apnea–Hypopnea Index (AHI); associations between baseline sleep parameters and cognitive trajectories were examined. And the association of sleep variables with the use of CPAP was also evaluated. Results: Compared with non-users, CPAP users showed significantly slower global decline (Δ MMSE: p = 0.016) and improvements in overall cognition (Δ RBANS Total: p = 0.028) and RBANS sub-domains (Δ RBANS FC: p = 0.010; Δ RBANS SF: p = 0.045). Longer baseline non-rapid eye movement (NREM) stage 3 and rapid eye movement (REM) sleep, greater total sleep time and sleep efficiency, and right-side sleeping were each linked to better cognitive outcomes, whereas extended NREM stage 2, wakefulness, and supine sleeping were associated with poorer trajectories. Conclusions: Twelve months of CPAP use was associated with attenuated cognitive decline and domain-specific gains in AD-related MCI with OSA. Sleep architecture and body position during sleep predicted cognitive outcomes, underscoring the therapeutic relevance of optimizing breathing and sleep quality. Larger, longer-term trials are warranted to confirm CPAP’s disease-modifying potential and to clarify the mechanistic role of sleep in AD progression. Full article

(This article belongs to the Special Issue Early Biomarker Identification and Treatment Strategy for Alzheimer's Disease)

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13 pages, 3028 KB

Open AccessArticle

Structural Brain Abnormalities, Diagnostic Approaches, and Treatment Strategies in Vertigo: A Case-Control Study

by Klaudia Széphelyi, Szilvia Kóra, Gergely Orsi and József Tollár

Neurol. Int. 2025, 17(9), 146; https://doi.org/10.3390/neurolint17090146 - 10 Sep 2025

Abstract

Background/Objectives: Dizziness is a frequent medical complaint with neurological, otolaryngological, and psychological origins. Imaging studies such as CT (Computer Tomography), cervical X-rays, and ultrasound aid diagnosis, while MRI (Magnetic Resonance Imaging) is crucial for detecting brain abnormalities. Our purpose is to identify structural [...] Read more.

Background/Objectives: Dizziness is a frequent medical complaint with neurological, otolaryngological, and psychological origins. Imaging studies such as CT (Computer Tomography), cervical X-rays, and ultrasound aid diagnosis, while MRI (Magnetic Resonance Imaging) is crucial for detecting brain abnormalities. Our purpose is to identify structural brain changes associated with vertigo, assess pre-MRI diagnostic approaches, and evaluate treatment strategies. Methods: A case-control study of 232 vertigo patients and 232 controls analyzed MRI findings, pre-MRI examinations, symptoms, and treatments. Statistical comparisons were performed using chi-square and t-tests (p < 0.05). Results: White matter lesions, lacunar infarcts, Circle of Willis variations, and sinusitis were significantly more frequent in vertigo patients (p < 0.05). Pre-MRI diagnostics frequently identified atherosclerosis (ultrasound) and spondylosis (X-ray). Common symptoms included headache, imbalance, and visual disturbances. The most frequent post-MRI diagnosis was Benign Paroxysmal Positional Vertigo (BPPV). Treatments included lifestyle modifications, physical therapy (e.g., Epley maneuver), and pharmacological therapies such as betahistine. Conclusions: MRI revealed structural brain changes linked to vertigo. Pre-MRI assessments are essential for ruling out vascular and musculoskeletal causes. A multidisciplinary treatment approach is recommended. Trial Registration: This study was registered in ClinicalTrials.gov with the trial registration number NCT06848712 on 22 February 2025. Full article

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14 pages, 689 KB

Open AccessArticle

Biological Plausibility of Using Plasma Amino Acid Profile Determination as a Potential Biomarker for Pediatric Patients with Mild Traumatic Brain Injuries

by Adán Pérez-Arredondo, Eduardo Cázares-Ramírez, Luis Tristán-López, Carlos Jiménez-Gutiérrez, Diana L. Pérez-Lozano, Ivette A. Martínez-Hernández, Valentina Vega-Rangel, Hugo F. Narváez-González, Camilo Rios, Marina Martínez-Vargas, Luz Navarro and Liliana Carmona-Aparicio

Neurol. Int. 2025, 17(9), 145; https://doi.org/10.3390/neurolint17090145 - 9 Sep 2025

Abstract

Background: Amino acid biomarkers have a crucial influence on our understanding of brain injury mechanisms, and their plasma concentrations may indicate neurological damage and recovery patterns. Pediatric mild traumatic brain injury (mTBI) assessment particularly benefits from such molecular indicators, as clinical presentations can [...] Read more.

Background: Amino acid biomarkers have a crucial influence on our understanding of brain injury mechanisms, and their plasma concentrations may indicate neurological damage and recovery patterns. Pediatric mild traumatic brain injury (mTBI) assessment particularly benefits from such molecular indicators, as clinical presentations can be subtle and variable. However, current diagnostic and prognostic tools lack reliable biochemical markers that can track the temporal evolution of injuries and recovery. Methods: We conducted a prospective longitudinal cohort study involving 36 pediatric mTBI patients and 44 controls to characterize the temporal evolution of key amino acids and their derived indices. Blood samples were collected at 3, 6, 12, and 24 h and at 7, 14, and 28 days post-injury, with amino acids quantified using high-performance liquid chromatography. Results: Our analysis revealed significant temporal changes in glutamate, glutamine, and glycine concentrations, with glutamate peaking at day 7 before declining, while glutamine showed steady increases throughout. The GLN/GLU ratio demonstrated an early excitatory imbalance followed by astrocytic compensation, and the GLX ratio indicated progressive recovery. Conclusions: These patterns represent continuous neurochemical processes involving excitotoxicity and glial regulation, suggesting potential utility as biomarkers for mTBI diagnosis and monitoring. While further validation using larger cohorts is needed, these findings provide compelling evidence of the efficacy of using amino acid profiles to track pediatric mTBI progression and recovery. Full article

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

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13 pages, 524 KB

Open AccessArticle

Plasma Neurofilament Light Chain Is Associated with Cognitive Functions but Not Patient-Reported Outcomes in Multiple Sclerosis

by Valerio Nicolella, Federica Novarella, Fabrizia Falco, Carmela Polito, Rosa Sirica, Evelina La Civita, Vincenzo Criscuolo, Giuseppe Corsini, Antonio Luca Spiezia, Alessia Castiello, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Giuseppe Castaldo, Vincenzo Brescia Morra, Daniela Terracciano and Marcello Moccia

Neurol. Int. 2025, 17(9), 144; https://doi.org/10.3390/neurolint17090144 - 9 Sep 2025

Abstract

Objective: We aimed to explore associations between plasma neurofilament light chain (pNfL) and cognition through patient-reported outcomes (PROs) in multiple sclerosis (MS). Methods: In this cross-sectional study, we included 211 people with MS (PwMS) and collected data from pNfL (fully automated chemiluminescent enzyme [...] Read more.

Objective: We aimed to explore associations between plasma neurofilament light chain (pNfL) and cognition through patient-reported outcomes (PROs) in multiple sclerosis (MS). Methods: In this cross-sectional study, we included 211 people with MS (PwMS) and collected data from pNfL (fully automated chemiluminescent enzyme immunoassay), EDSS, education, cognition (the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT II), and Brief Visuospatial Memory Test–Revised (BVMT-R)), the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI). Results: On multivariate linear regression models, higher educational attainment was significantly associated with lower pNfL (high school: Coeff = −0.22, 95% CI = −0.41 to −0.04, p = 0.019; university: Coeff = −0.22, 95% CI = −0.42 to −0.02, p = 0.030). In logistic regression models, the likelihood of having pNfL levels above normal thresholds increased by 56% for each one-point increment in the EDSS score (OR = 1.56, 95% CI = 1.23 to 1.98, p < 0.001) and was 2.5 times greater in individuals with impaired SDMT (OR = 2.50, 95% CI = 2.20 to 5.21, p = 0.014). No statistically significant associations were observed between pNfL and CVLT-II, BVMT-R, BDI-II, MFIS, BAI, or PSQI. Conclusions: Neuro-axonal damage in people with MS manifests clinically as increased disability and reduced attention and processing speed. However, these effects may be mitigated by greater brain resilience, as suggested by the protective role of higher educational attainment. The PROs assessed in this study showed no significant associations with pNfL levels, possibly due to measurement errors and heterogeneity, with limited sensitivity to neuro-axonal damage. Full article

(This article belongs to the Section Aging Neuroscience)

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15 pages, 869 KB

Open AccessReview

Pericapsular Nerve Group Block Versus Lumbar Epidural Block for Pain Management After Hip Surgeries with a Focus on Pediatric Patients: A Narrative Review

by Shahab Ahmadzadeh, Hunter M. Schwab, Mary O’Dell Duplechin, Kalob M. Broocks, Jon D. Hirsch, Joseph Drinkard and Sahar Shekoohi

Neurol. Int. 2025, 17(9), 142; https://doi.org/10.3390/neurolint17090142 - 8 Sep 2025

Abstract

Pediatric hip surgeries are associated with moderate to high levels of pain, which, in severe cases can lead to opioid prescription and use. There is a growing focus on reducing post-operative pain in these patients to decrease the need for opioids, as well [...] Read more.

Pediatric hip surgeries are associated with moderate to high levels of pain, which, in severe cases can lead to opioid prescription and use. There is a growing focus on reducing post-operative pain in these patients to decrease the need for opioids, as well as increase early mobilization for recovery. Conventional methods of pain relief using opioids can have unwanted negative impacts on pediatric patients such as respiratory depression, nausea, confusion, and the concerning possibility for the development of dependence. Likewise, traditional methods of anesthesia, like the lumbar epidural block, can have unwanted systemic side effects, such as hypotension, urinary retention, arrhythmias, and spinal abscesses. These complications can lead to longer hospital stays and delayed recovery. This review analyzes the efficacy of a newer regional anesthesia technique, the pericapsular nerve group (PENG) block, in comparison to the lumbar epidural block. This technique utilizes precision-based anesthesia to selectively block the articular branches to the hip joint while avoiding the main trunks of the femoral and obturator nerves. Additionally, with the utilization of high-resolution ultrasound to guide the blocks, providers can increasingly count on proper insertion and predictable anesthetic spread. The result is a motor-sparing blockade that shows promise in allowing earlier mobilization and better functional recovery times after pediatric hip surgeries. Full article

(This article belongs to the Section Pain Research)

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13 pages, 4892 KB

Open AccessCase Report

Hyperkinetic Movement Disorder in KARS1-Related Disease: An Illustrative Video-Recorded Case and Narrative Literature Review

by Veronica Ferasin, Arianna Raicich, Caterina Ancora, Ilaria Bonemazzi, Alessandro Di Paola, Ignazio D’Errico, Margherita Nosadini, Claudio Ancona, Maria Federica Pelizza, Matteo Cassina and Irene Toldo

Neurol. Int. 2025, 17(9), 143; https://doi.org/10.3390/neurolint17090143 - 7 Sep 2025

Abstract

Background: Aminoacyl-tRNA synthetases (ARSs) are a group of enzymes responsible for the first step of protein translation. Among them, the KARS1 gene encodes lysyl-tRNA synthetase 1, an enzyme essential for charging tRNA-Lys with lysine in both the cytoplasm and mitochondria. Mutations in KARS1 [...] Read more.

Background: Aminoacyl-tRNA synthetases (ARSs) are a group of enzymes responsible for the first step of protein translation. Among them, the KARS1 gene encodes lysyl-tRNA synthetase 1, an enzyme essential for charging tRNA-Lys with lysine in both the cytoplasm and mitochondria. Mutations in KARS1 are associated with a wide range of clinical phenotypes, including leukoencephalopathy, hereditary deafness, peripheral neuropathies, and multisystemic involvement. Methods: We hereby report a detailed case study of a 15-month-old boy presenting at age 5 months with developmental delay, microcephaly, hypotonia, sensorineural deafness, retinopathy, visual impairment, nystagmoid eye movements, and hepatic and immuno-hematological abnormalities. In addition, he exhibited a severe hyperkinetic movement disorder, not previously reported in the literature, and developed epilepsy at 13 months. Genetic testing identified two rare compound heterozygous variants in the KARS1 gene. Results: With this report, we aim to contribute to the expanding of both the clinical phenotype and the allelic spectrum of lysyl-tRNA synthetase-related disorders. Our study also includes a review of previously described KARS1 cases presenting with movement disorders. Conclusions: Our findings further highlight the importance of assessing systemic involvement and performing brain and spinal neuroimaging, as well as implementing genetic screening, in infants presenting with global developmental delay, sensory deficits, and movement disorders—features that may suggest a mitochondrial disorder such as those involving ARS mutations. Full article

(This article belongs to the Special Issue New Insights into Movement Disorders)

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21 pages, 1777 KB

Open AccessReview

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges

by Aleksandar Sic, Conor George, Daniela Ferrer Gonzalez, Vasilis-Spyridon Tseriotis and Nebojsa Nick Knezevic

Neurol. Int. 2025, 17(9), 141; https://doi.org/10.3390/neurolint17090141 - 5 Sep 2025

Abstract

Cannabinoids have gained increasing attention as potential therapeutic agents in chronic pain management. Their mechanisms of action, mediated through CB1 and CB2 receptors, provide a pharmacological alternative to conventional analgesics. The evidence is strongest for neuropathic pain and multiple sclerosis-related spasticity, while the [...] Read more.

Cannabinoids have gained increasing attention as potential therapeutic agents in chronic pain management. Their mechanisms of action, mediated through CB1 and CB2 receptors, provide a pharmacological alternative to conventional analgesics. The evidence is strongest for neuropathic pain and multiple sclerosis-related spasticity, while the results for fibromyalgia, osteoarthritis, and musculoskeletal pain remain inconsistent. The average pain reduction is modest, often not exceeding 0.5–1.0 points on a 10-point scale, and therapeutic gains are offset by safety concerns. Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, while nabiximols (THC + CBD spray) are associated with dizziness in 25% of patients, somnolence in 8%, and treatment discontinuation in 12%. High-dose CBD also carries a measurable risk of hepatotoxicity. Regulatory heterogeneity further constrains trial feasibility, scalability, and patient access, with disparities evident across the United States, Europe, Canada, and Australia. Overall, cannabinoids provide modest, condition-specific analgesia and should be considered adjunctive rather than first-line options, reserved for patients unresponsive to conventional therapy. Future progress requires standardized formulations, harmonized international regulations, long-term safety data, and large-scale randomized controlled trials to clarify their role in evidence-based pain management. Full article

(This article belongs to the Section Pain Research)

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23 pages, 1536 KB

Open AccessArticle

Epidemiological and Clinical Characteristics of Acute Stroke in a Multi-Ethnic South Asian Population

by Kim H. Tran, Naveed Akhtar, Yahia Imam, Md Giass Uddin, Sujatha Joseph, Deborah Morgan, Blessy Babu, Ryan Ty Uy and Ashfaq Shuaib

Neurol. Int. 2025, 17(9), 140; https://doi.org/10.3390/neurolint17090140 - 5 Sep 2025

Abstract

Objective: Stroke is one of the leading causes of death and disability worldwide. Compared to developed countries, the prognosis of stroke is less favourable in developing countries. The objective of this study is to identify inter-ethnic variation in risk profiles and stroke outcomes [...] Read more.

Objective: Stroke is one of the leading causes of death and disability worldwide. Compared to developed countries, the prognosis of stroke is less favourable in developing countries. The objective of this study is to identify inter-ethnic variation in risk profiles and stroke outcomes amongst Bangladeshi, Indian, Nepalese, Pakistani, and Sri Lankan expatriates living in Qatar. Methods: Data from the Qatar Stroke Registry were retrospectively analyzed from April 2014 to June 2025. A total of 8825 patients were included. The chi-square test was used to analyze sociodemographic variables, while the Kruskal–Wallis test was used to analyze continuous variables. Post hoc analysis was performed. Multivariate logistic regression and multivariate multiple regression were used to identify the predictors associated with poor clinical outcomes and mortality at 90 days. Results: Ischemic stroke was the predominant stroke type in all groups, with Nepalese patients presenting with stroke at a younger age, whilst Pakistanis tended to be older (p < 0.001). In terms of stroke outcomes, Nepalese patients had the highest proportion of a poor functional outcome at 90 days as well as NIHSS at discharge (p < 0.05). However, Bangladeshis had the highest proportion of mortality at 90 days compared to the other cohorts. Multivariable logistic regression revealed that undiagnosed dyslipidemia, Nepalese ethnicity, and moderate and severe NIHSS admission scores were independent predictors of a poor functional outcome at 90 days, whilst male sex and prior antidiabetic therapy were protective factors (p < 0.001). In terms of mortality at 90 days, only a severe NIHSS admission score (>10) was a significant predictor (p < 0.001). A severe NIHSS admission score was also the only predictive factor of mortality and poor functional outcome at 90 days (p < 0.05). Conclusions: There was a significant variation in stroke presentation and outcomes among South Asian subpopulations in Qatar, suggesting the importance of tailored public health strategies as a uniform approach to stroke care is insufficient for this diverse population. Full article

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

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