Neurology International最新文献

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.

Background: Urinary continence relies on a complex interplay between urine storage and voiding involving both spinal reflex circuits and supraspinal brain areas to coordinate volun-tary 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 bladder filling.

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 bladder filling. 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.

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.

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.

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.

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.

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.

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.

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.

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.