Editor’s Choice Articles

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

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

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

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

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

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

Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico. Full article

Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV, as well as hypertension classification and stages and demographic characteristics. Methods: A total of 1201 medical records from patients collected over a 6-year span who first presented with R-BPPV were retrospectively evaluated regarding blood pressure (BP) presentation and associated risk factors. R-BPPV included patients treated with necessary canalith repositioning procedures (CRPs) and followed up with for 12 months. The RO and RR were evaluated when comparing patients sub-grouped by current classification and staging. The association between the RO and RR and many prognostic factors, including the presence of cardio- and neuro-vascular risks, was examined via multiple regression analysis. Results: Among the 857 included patients with R-BPPV, 211 presented with an optimal/normal BP, 210 were found to have a high–normal BP, 222 were classified with Grade 1 hypertension, and 214 were found to have Grade 2 hypertension. Significant (p < 0.05) progressive earlier presentations and increases in needed CRPs were found with the respective increase in BP subgroups. For the RO, the correlation was statistically significant for age and gender, while for the RR, the correlation was statistically significant for age and hypertension stage. Conclusions: This study demonstrates for the first time that clinical consequences of R-BPPV are strongly associated with cardio-, neuro-vascular, and socio-demographic risk factors, which are commonly involved in R-BPPV occurrence. Full article

Background/Objectives: Cognitive decline has been increasingly linked to cardiac autonomic regulation; however, its specific associations with cognitive domains, such as information processing speed and executive function, remain unclear. This preliminary study examined the relationship between cardiac autonomic modulation and cognitive performance in older adults. Methods: A cross-sectional study was conducted with 101 older adults (aged ≥60 years) attending a university hospital outpatient clinic. Participants were classified as without cognitive impairment (WCI) or cognitively impaired and not demented (CIND) based on neuropsychological assessments. Heart rate variability (HRV) was measured at rest, focusing on the time-domain parameters (SDNN, rMSSD, and pNN50). Trail making test parts A and B (TMT-A and TMT-B) were used to assess information processing speed and executive function, respectively. Analyses of covariance (ANCOVAs) were performed, adjusting for confounding variables including age, sex, and comorbidities. Results: Participants in the CIND group had significantly lower HRV indices than those in the WCI group (SDNN, p < 0.05, d = 0.44; rMSSD, p < 0.05, d = 0.39; pNN50, p < 0.05, d = 0.40), indicating reduced parasympathetic modulation. Higher HRV values were observed in individuals with preserved processing speed and executive function. Specifically, pNN50 was significantly associated with processing speed (p = 0.04), and SDNN was significantly correlated with executive function (p = 0.02). These associations persisted even after adjusting for confounding factors. Conclusions: Reduced cardiac autonomic modulation, especially lower parasympathetic activity, is significantly associated with cognitive impairment in older adults. Lower pNN50 values were correlated with slower information processing speed, and lower SDNN was associated with poorer executive function. These findings support the potential use of HRV as a physiological biomarker to detect cognitive changes during ageing. Full article

Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (p = 0.0016 and p = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (p = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (p = 0.0098), whereas aspirin monotherapy and combination therapy did not (p = 0.1009 and p = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (p = 0.0002 and p = 0.0001, respectively), whereas combined therapy revealed no significant benefit (p = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy. Full article

Background/Objectives: A subtype of cerebral amyloid angiopathy (CAA), iatrogenic CAA (iCAA), has been increasingly reported. iCAA occurs primarily in patients who underwent surgery during childhood and is caused by the prion-like propagation of amyloid beta. This subtype of CAA tends to develop at a younger age than age-related CAA, usually before the age of 55. After a latency period of 20–40 years following surgery, it manifests as lobar intracerebral hemorrhage (ICH), cognitive impairment, or transient focal neurological episodes. Between 2023 and 2024, we observed four cases of possible iCAA, all of which had a history of neurosurgery during childhood. Case presentation: MRI findings for all cases revealed multiple lobar microbleeds. Two cases also showed cortical superficial siderosis and lobar ICH. Notably, contrast-enhanced 3D FLAIR demonstrated sulcal enhancement in two cases, and CT demonstrated cortical calcification in the bilateral posterior lobes in one case. Conclusions: Sulcal enhancement on contrast-enhanced 3D FLAIR and cortical calcification in the bilateral posterior lobes on CT may suggest advanced CAA in the present cases. Full article

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors associated with its efficacy. Methods: There are four reasons for prescribing lasmiditan: as an add-on to triptan, if triptan is ineffective, if triptan produces side effects, and when triptan is contraindicated. Lasmiditan was administered at a dose of 50 mg. The efficacy of lasmiditan was defined as the disappearance of headache or a 50% or greater reduction in headache intensity within two hours after dosing. This study included 108 patients with migraines who took lasmiditan. Results: The results for efficacy and the side effects of lasmiditan were as follows: effective without side effects (22), effective with mild side effects (32), ineffective (14), and severe side effects (40). The efficacy rate of lasmiditan 50 mg was 50.0% (54/108). The following factors were found to be associated with lasmiditan’s efficacy: sex, migraine classification, calcium channel blockers, and anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment. The overall incidence of side effects was 66.7%, and the dropout rate was 37.0%. Somnolence was more prevalent in the effective group, and other side effects were more prevalent in patients who dropped out due to the side effects of lasmiditan. Conclusions: Lasmiditan is likely to be effective in males with severe migraine classification and receiving CGRP-mAb treatment. If mild somnolence is a side effect, the drug can be continued and may be effective. Full article

Background: Chronic aberrant inflammation is a crucial step in mediating cerebrovascular and neurodegenerative pathologies, including Alzheimer’s and Parkinson’s disease. Due to their exceptional antioxidant properties and ability to alter imbalance metabolism and reactive inflammation response, cocoa-derived flavanols are being investigated as potential bioactive substances to modulate and reverse these inflammation-associated disorders. Objective: The present study will focus on the possible beneficial effects of cocoa-derived extract, enhanced with other bioactive phytochemicals such as spirulina and pineapple, on selected biomarkers of the inflammatory, metabolic, and neurodegenerative processes. Methods: A mice model of inflammation was treated with cocoa-derived extract cocktail, and biomolecular data was obtained by performing immunohistochemical and biochemical analysis. Results: Results show that the cocoa-derived extract mitigates the neuroinflammatory processes triggered (decreased expression of macrophage CD11b) and prevents the escalade of subsequent neurodegeneration pathologies. Conclusions: The results based on hypo-vitaminosis, neuroinflammation, and inmunoreactive analysis suggest that cocoa-derived extract is a powerful bioproduct for ameliorating neuroinflammatory processes that mediate metabolic and cerebrovascular diseases. Full article

Point-of-care electroencephalography (POC-EEG) systems are rapid-access, reduced-montage devices designed to address the limitations of conventional EEG (conv-EEG), enabling faster neurophysiological assessment in acute settings. This review evaluates their clinical impact, diagnostic performance, and feasibility in non-convulsive status epilepticus (NCSE), traumatic brain injury (TBI), stroke, and delirium. A comprehensive search of Medline, Scopus, and Embase identified 69 studies assessing 15 devices. In suspected NCSE, POC-EEG facilitates rapid seizure detection and prompt diagnosis, making it particularly effective in time-sensitive and resource-limited settings. Its after-hours availability and telemedicine integration ensure continuous coverage. AI-assisted tools enhance interpretability and accessibility, enabling use by non-experts. Despite variability in accuracy, it supports triaging, improving management, treatment decisions and outcomes while reducing hospital stays, transfers, and costs. In TBI, POC-EEG-derived quantitative EEG (qEEG) indices reliably detect structural lesions, support triage, and minimize unnecessary CT scans. They also help assess concussion severity and predict recovery. For strokes, POC-EEG aids triage by detecting large vessel occlusions (LVOs) with high feasibility in hospital and prehospital settings. In delirium, spectral analysis and AI-assisted models enhance diagnostic accuracy, broadening its clinical applications. Although POC-EEG is a promising screening tool, challenges remain in diagnostic variability, technical limitations, and AI optimization, requiring further research. Full article

Background: Pain is prevalent in almost all populations and may often hinder visual, auditory, tactile, olfactory, and taste perception as it alters brain neural processing. The quantitative methods emerging to define pain and assess its effects on neural functions and perception are important. Identifying pain biomarkers is one of the initial stages in developing such models and interventions. The existing literature has explored chronic and experimentally induced pain, leveraging electroencephalograms (EEGs) to identify biomarkers and employing various qualitative and quantitative approaches to measure pain. Objectives: This systematic review examines the methods, participant characteristics, types of pain states, associated pain biomarkers of the brain’s electrical activity, and limitations of current pain studies. The review identifies what experimental methods researchers implement to study human pain states compared to human control pain-free states, as well as the limitations in the current techniques of studying human pain states and future directions for research. Methods: The research questions were formed using the Population, Intervention, Comparison, Outcome (PICO) framework. A literature search was conducted using PubMed, PsycINFO, Embase, the Cochrane Library, IEEE Explore, Medline, Scopus, and Web of Science until December 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to obtain relevant studies. The inclusion criteria included studies that focused on pain states and EEG data reporting. The exclusion criteria included studies that used only MEG or fMRI neuroimaging techniques and those that did not focus on the evaluation or assessment of neural markers. Bias risk was determined by the Newcastle–Ottawa Scale. Target data were compared between studies to organize the findings among the reported results. Results: The initial search resulted in 592 articles. After exclusions, 24 studies were included in the review, 6 of which focused on chronic pain populations. Experimentally induced pain methods were identified as techniques that centered on tactile perception: thermal, electrical, mechanical, and chemical. Across both chronic and stimulated pain studies, pain was associated with decreased or slowing peak alpha frequency (PAF). In the chronic pain studies, beta power increases were seen with pain intensity. The functional connectivity and pain networks of chronic pain patients differ from those of healthy controls; this includes the processing of experimental pain. Reportedly small sample sizes, participant comorbidities such as neuropsychiatric disorders and peripheral nerve damage, and uncontrolled studies were the common drawbacks of the studies. Standardizing methods and establishing collaborations to collect open-access comprehensive longitudinal data were identified as necessary future directions to generalize neuro markers of pain. Conclusions: This review presents a variety of experimental setups, participant populations, pain stimulation methods, lack of standardized data analysis methods, supporting and contradicting study findings, limitations, and future directions. Comprehensive studies are needed to understand the pain and brain relationship deeper in order to confirm or disregard the existing findings and to generalize biomarkers across chronic and experimentally induced pain studies. This requires the implementation of larger, diverse cohorts in longitudinal study designs, establishment of procedural standards, and creation of repositories. Additional techniques include the utilization of machine learning and analyzing data from long-term wearable EEG systems. The review protocol is registered on INPLASY (# 202520040). Full article

Neurological diseases are increasingly diverse and prevalent, presenting significant challenges for their timely and accurate diagnosis. The aim of the present study is to conduct a bibliometric analysis and literature review in the field of neurology to explore advancements in the application of artificial intelligence (AI) techniques, including machine learning (ML) and deep learning (DL). Using VOSviewer software (version 1.6.20.0) and documents retrieved from the Scopus database, the analysis included 113 articles published between 1 January 2018 and 31 December 2024. Key journals, authors, and research collaborations were identified, highlighting major contributions to the field. Science mapping investigated areas of research focus, such as biomechanical data and gait analysis including AI methodologies for neurological disease diagnosis. Co-occurrence analysis of author keywords allowed for the identification of four major themes: (a) machine learning and gait analysis; (b) sensors and wearable health technologies; (c) cognitive disorders; and (d) neurological disorders and motion recognition technologies. The bibliometric insights demonstrate a growing but relatively limited collaborative interest in this domain, with only a few highly cited authors, documents, and journals driving the research. Meanwhile, the literature review highlights the current methodologies and advancements in this field. This study offers a foundation for future research and provides researchers, clinicians, and occupational therapists with an in-depth understanding of AI’s potentially transformative role in neurology. Full article

Background/Objectives: Blast-induced traumatic ocular injuries (bTOI) pose a significant risk to military and civilian populations, often leading to visual impairment or blindness. Retina, the innermost layer of ocular tissue consisting of photoreceptor and glial cells, is highly susceptible to blast injuries. Despite its prevalence, the molecular mechanisms underlying retinal damage following bTOI remain poorly understood, hindering the development of targeted therapies. Melatonin, a neuroprotective indoleamine with antioxidant, anti-inflammatory, and circadian regulatory properties, is synthesized in the retina and plays a crucial role in retinal health. Similarly, retina-specific genes, such as Rhodopsin, Melanopsin, and RPE65, are essential for photoreceptor function, visual signaling, and the visual cycle. However, their responses to blast exposure have not been thoroughly investigated. Methods: In this study, we utilized a ferret model of bTOI to evaluate the temporal expression of melatonin-synthesizing enzymes, such as tryptophan hydroxylase 1 and 2 (TPH1 and TPH2), Aralkylamine N-acetyltransferase (AANAT), and Acetylserotonin-O-methyltransferase (ASMT), and retina-specific genes (Rhodopsin, Melanopsin) and retinal pigment epithelium-specific 65 kDa protein (RPE65) at 4 h, 24 h, 7 days, and 28 days post-blast. Ferrets were exposed to tightly coupled blast overpressure waves using an advanced blast simulator, and retinal tissues were collected for quantitative polymerase chain reaction (qPCR) analysis. Results: The results revealed dynamic and multiphasic transcriptional responses. TPH1 and TPH2 exhibited significant upregulation at 24 h, followed by downregulation at 28 days, indicating blast-induced dysregulation of tryptophan metabolism, including melatonin synthesis. Similarly, AANAT and ASMT showed acute downregulation post-blast, with late-phase disruptions. Rhodopsin expression increased at 24 h but declined at 28 days, while Melanopsin and RPE65 demonstrated early upregulation followed by downregulation, reflecting potential disruptions in circadian regulation and the visual cycle. Conclusions: These findings highlight the complex regulatory mechanisms underlying retinal responses to bTOI, involving neuroinflammation, oxidative stress, and disruptions in melatonin synthesis and photoreceptor cell functions. The results emphasize the therapeutic potential of melatonin in mitigating retinal damage and preserving visual function. Full article

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletions or mutations in the SMN1 gene, leading to progressive motor neuron degeneration. While SMA has been classically viewed as a motor neuron-autonomous disease, increasing evidence indicates a significant role of glial cells—astrocytes, microglia, oligodendrocytes, and Schwann cells—in the disease pathophysiology. Astrocytic dysfunction contributes to motor neuron vulnerability through impaired calcium homeostasis, disrupted synaptic integrity, and neurotrophic factor deficits. Microglia, through reactive gliosis and complement-mediated synaptic stripping, exacerbate neurodegeneration and neuroinflammation. Oligodendrocytes exhibit impaired differentiation and metabolic support, while Schwann cells display abnormalities in myelination, extracellular matrix composition, and neuromuscular junction maintenance, further compromising motor function. Dysregulation of pathways such as NF-κB, Notch, and JAK/STAT, alongside the upregulation of complement proteins and microRNAs, reinforces the non-cell-autonomous nature of SMA. Despite the advances in SMN-restorative therapies, they do not fully mitigate glial dysfunction. Targeting glial pathology, including modulation of reactive astrogliosis, microglial polarization, and myelination deficits, represents a critical avenue for therapeutic intervention. This review comprehensively examines the multifaceted roles of glial cells in SMA and highlights emerging glia-targeted strategies to enhance treatment efficacy and improve patient outcomes. Full article

Background: Changes in the daily rhythm can trigger migraine attacks. The sensitivity for triggering attacks is closely linked to the regulation of biological rhythms controlled by the hypothalamus. In over 70 countries around the world, the time is changed between daylight savings time and standard time twice a year due to legal regulations. The aim of this study was to investigate whether the time change has an influence on migraine. Methods: In this retrospective study, the headache frequency of patients with episodic or chronic migraine at a tertiary headache center in the years 2020, 2021, and 2022 was evaluated. The primary outcome measure was the frequency of migraine occurrence on either Sunday or Monday of the time change weekend compared to Sunday or Monday before or Sunday or Monday after the time change. Results: Data from 258 patients were analyzed (86.8% women; average age: 51.5 years; average headache frequency: 7.7 days/month; 83.3% episodic migraine). Our results showed a significant increase of 6.4% in migraine frequency on the Sunday and/or Monday in the week after the time change in spring compared to the week before the change. In autumn, conversely, there was a significant reduction of 5.5% in migraine frequency on the Sunday and/or Monday one week after the time change compared to the week before the change. The factor responsible for the significant changes was the increase in migraines on Monday one week after the time change in spring and the decrease in migraines on Sunday one week after the time change in autumn. Conclusions: When switching from standard time to daylight savings time in the spring, the frequency of migraines increases significantly one week after the time change. In autumn, in comparison, there is an inverse trend with a reduction in migraine frequency. These data suggest that synchronization is disturbed when switching to daylight savings time. Conversely, synchronization normalizes in autumn. In view of the high prevalence of migraines, this can have extensive individual and social consequences. Full article

Objective: Seizures are a critical public health issue, with incidence rising significantly after age 50. Using this inflection point, we divided patients into two age groups to examine the impact of age on patient characteristics and hospitalization outcomes for seizures. Methods: Using the 2021 National Inpatient Sample (NIS), a nationally representative database, we conducted a retrospective cohort analysis of adult patients aged ≥18 years admitted with a principal diagnosis of seizures. Patients were divided into two age groups: 18–49 and ≥50 years. Outcomes included in-hospital mortality, length of stay, and hospital charges. Multivariate logistic and linear regression models adjusted for confounders were employed to assess the association between age and outcomes. Results: The cohort included 211,055 patients, with 59% aged ≥50 years. Older patients were more likely to have Medicare coverage (66% vs. 16%, p < 0.01), to reside in the south (41% vs. 38%, p < 0.01), and to have a higher proportion of White individuals (62% vs. 54%, p < 0.01). Younger patients were more likely to be Hispanic (15% vs. 9%, p < 0.01), admitted to urban hospitals (96% vs. 94%, p < 0.01), and treated at teaching hospitals (84% vs. 79%, p < 0.01). After adjusting for confounders, older adults had over twice the odds of in-hospital mortality compared with younger patients (adjusted OR 2.17; 95% CI, 1.61–2.92; p < 0.01). They also experienced longer hospital stays (mean difference 0.7 days; 95% CI, 0.54–0.92; p < 0.01) and higher hospital charges (mean increase USD 4322; 95% CI, USD 1914–6731; p < 0.01). Significance: Age is an independent predictor of in-hospital mortality, longer hospitalizations, and higher costs in seizure-related admissions. These findings underscore the need for age-specific management strategies to improve outcomes and optimize healthcare resource utilization for older adults with seizures. Full article

Background/Objectives: Epilepsy is one of the most common chronic neurological disorders, characterized by alterations in neuronal electrical activity that result in recurrent seizures and involuntary body movements. Anticonvulsants are the primary treatment for this condition, helping patients improve their quality of life. However, the development of new drugs with fewer side effects and greater economic accessibility remains a key focus in nanomedicine. Macamides, secondary metabolites derived from Maca (Lepidium meyenii), represent a promising class of novel drugs with diverse therapeutic applications, particularly in the treatment of neurological disorders. Methods: In this study, we optimized the potential of the macamide N-3-methoxybenzyl-linoleamide (3-MBL) as an anticonvulsant agent through its encapsulation in PEGylated liposomes conjugated with OX26 F(ab′)₂ fragments. Results: These immunoliposomes exhibited a size of 120.52 ± 9.46 nm and a zeta potential of −8.57 ± 0.80 mV. Furthermore, in vivo tests using a pilocarpine-induced status epilepticus model revealed that the immunoliposomes provided greater efficacy against epileptic seizures compared to the free form of N-3-methoxybenzyl-linoleamide at the same dose. Notably, the observed anticonvulsant effect was comparable to that of carbamazepine, a traditional FDA-approved antiepileptic drug. Conclusions: This pioneering work employs liposomal nanocarriers to deliver macamides to the brain, aiming to set a new standard for the use of modified liposomes in anticonvulsant epilepsy treatment. Full article

The diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) is most difficult in patients who are in good clinical condition with a small hemorrhage, especially when a ruptured aneurysm might not be considered, or if a computed tomographic (CT) scan is not obtained, or if when a CT is obtained, the findings are subtle and missed by an inexperienced reviewer. All acute onset (thunderclap) headaches should be considered ruptured aneurysms until proven otherwise. Treatment begins with immediate control of pain and blood pressure, placement of an external ventricular drain (EVD) in poor-grade patients and those with acute hydrocephalus on CT scanning, administration of antifibrinolytic tranexamic acid, and then repair of the aneurysm with either surgical clipping or endovascular techniques as soon as the appropriate treatment team can be assembled. After securing the aneurysm, aSAH patient treatment is focused on maintaining euvolemia and a favorable systemic metabolic state for brain repair. A significant and aneurysm-specific threat after aSAH is delayed arterial vasospasm and resulting cerebral ischemia, which is detected by vigilant bedside examinations for new-onset focal deficits or neurological decline, assisted with daily transcranial Doppler examinations and the judicious use of vascular imaging and cerebral perfusion studies with CT. The management of diagnosed symptomatic vasospasm is the prompt induction of hypertension with vasopressors, but if this fails to reverse deficits quickly after reaching a target systolic blood pressure of 200 mmHg, endovascular angioplasty is indicated, providing CT scanning rules out an established cerebral infarction. Balloon angioplasty should be considered early for all patients found to have severe angiographic vasospasm, with or without detectable signs of ischemic neurological deterioration due to either sedation or a pre-existing deficit. Full article

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe neurocritical condition often complicated by cerebral vasospasm (CVS), leading to delayed cerebral ischemia (DCI) and significant morbidity and mortality. Despite advancements in management, therapeutic options with robust evidence remain limited. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, has emerged as a potential therapeutic option. Intravenous milrinone demonstrated clinical and angiographic improvement in 67% of patients, reducing the need for mechanical angioplasty and the risk of functional disability at 6 months (mRS ≤ 2). Side effects, including hypotension, tachycardia, and electrolyte disturbances, were observed in 33% of patients, occasionally leading to early drug discontinuation. Based on the evidence, we propose a treatment algorithm for using milrinone to optimize outcomes and standardize its application in neurocritical care settings. Full article

Objectives: Nonconvulsive status epilepticus (NCSE) is a disease with a high mortality rate and a very diverse etiology. The disease prognosis is related to the etiology. We aimed to investigate the etiology, mortality rates, and factors affecting mortality in patients diagnosed with NCSE in a tertiary epilepsy center in Turkey. Methods: All electroencephalograms (EEGs) were taken in the EEG laboratory of the Department of Neurology, Antalya Training and Research Hospital, between June 2021 and February 2024. Patients who met the Salzburg Consensus Criteria (SCC) for NCSE were included. Demographic data, etiologic factors, comorbidities, neuroradiological imaging, laboratory data, treatments administered for NCSE and responses to treatment, short- and long-term outcomes, and EEG findings at follow-up, if any, were noted from the medical records of all patients who met the criteria. Results: A total of 200 patients were included in the study. Mortality was observed in 76 (38.4%) patients with NCSE. There was a statistically significant correlation between NCSE etiology and mortality (p < 0.001). Mortality was most common in patients with cerebral tumors as the etiology, with a rate of 63.6%. The lowest mortality rate was observed in patients with autoimmune encephalitis and epilepsy (14.3% and 17.2%, respectively). After appropriate antiseizure medication (ASM) treatment, 117 (58.5%) patients with NCSE improved. When post-treatment improvement and etiologic factors were analyzed, the highest rate of improvement was observed in the autoimmune encephalitis and CVD groups. Conclusions: Our study showed that advanced age and the presence of stroke are associated with mortality and that patients with NCSE due to autoimmune encephalitis respond well to treatment. Full article

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates and the progressive and permanent loss of neurons are the major characteristic features of these disorders. Although the precise mechanisms causing Alzheimer’s disease (AD) and Parkinson’s disease (PD) are still unknown, there is a wealth of evidence suggesting that misfolded proteins, accumulation of misfolded proteins, dysfunction of neuroreceptors and mitochondria, dysregulation of enzymes, and the release of neurotransmitters significantly influence the pathophysiology of these diseases. There is no effective protective medicine or therapy available even with the availability of numerous medications. There is an urgent need to create new and powerful bioactive compounds since the number of people with NDDs is rising globally. Heterocyclic compounds have consistently played a pivotal role in drug discovery due to their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine hydrochloride, and opicapone, feature heterocyclic cores. As these heterocyclic compounds have exceptional therapeutic potential, heterocycles are an intriguing research topic for the development of new effective therapeutic drugs for PD and AD. This review aims to provide current insights into the development and potential use of heterocyclic compounds targeting diverse therapeutic targets to manage and potentially treat patients with AD and PD. Full article

Background: Peripheral facial paralysis (PFP) affects the facial nerve, the seventh cranial nerve. It has an incidence rate of 20–30 cases per 100,000 habitants. The diagnosis is clinical, though imaging tests may be required in some cases. The treatment protocol includes medication, physiotherapy, and, in certain cases, surgery. Proprioceptive neuromuscular facilitation (PNF) techniques and electrical stimulation have been shown to be significant for recovery. Although PFP has a high recovery rate, up to 40% of patients may experience permanent sequelae. Objective: to assess the efficacy of treatment based on electrical stimulation and/or PNF in patients affected by PFP. Methods: A systematic search was conducted across six databases (PubMed, Medline, SportDiscus, CINAHL, Scopus, and Web of Science) in November 2024. Randomized controlled trials were included. Results: Fourteen articles were analyzed, applying PNF and/or electrical stimulation methods, pharmacological treatment, low-level laser treatment, subcutaneous collagen injections, and physiotherapy protocols involving facial expression exercises, yielding evidence for the variables assessed. Conclusions: PNF and/or electrical stimulation treatment in patients with PFP can be effective when employed early with appropriate parameters, showing promising results in improving quality of life, facial movement quality, and CMAP and reducing both the incidence and degree of synkinesis. Full article

Background: Central facial palsy (CFP), resulting from upper motor neuron lesions in the corticofacial pathway, is traditionally characterized by the sparing of the upper facial muscles. However, reports of upper facial weakness in CFP due to acute ischemic stroke have challenged this long-held assumption. This study aimed to determine the prevalence of upper facial weakness in CFP and identify its associated clinical factors. Methods: In this cross-sectional study, we evaluated consecutive patients with acute ischemic stroke admitted to a university hospital in Thailand from January 2022 to June 2023. Full-face video recordings were analyzed using the Sunnybrook Facial Grading System. Upper facial weakness was defined as asymmetry in at least one upper facial expression. Multivariable logistic regression was performed to identify factors associated with upper facial weakness. Results: Of 108 patients with acute ischemic stroke, 92 had CFP, and among these, 70 (76%) demonstrated upper facial weakness. Tight eye closure (force and wrinkle formation, both 42%) was the most sensitive indicator for detecting upper facial weakness. Greater stroke severity, as reflected by higher NIHSS scores (adjusted odds ratio [aOR], 1.42; 95% CI 1.07–1.88) and the presence of lower facial weakness (aOR, 6.56; 95% CI 1.85–23.29) were significantly associated with upper facial involvement. Although upper facial weakness was generally milder than lower facial weakness, its severity correlated with increasing lower facial asymmetry during movement. Conclusions: Contrary to traditional teaching, upper facial weakness is common in CFP due to acute ischemic stroke. The severity of stroke and the presence of lower facial weakness are key predictors of upper facial involvement. These findings underscore the need for clinicians to reconsider the diagnostic paradigm, recognizing that upper facial weakness can occur in CFP. Enhanced awareness may improve diagnostic accuracy, inform treatment decisions, and ultimately lead to better patient outcomes. Full article

Cerebral venous thrombosis (CVT) is a rare and potentially critical cerebrovascular disease involving intracranial dural sinuses and veins. The diagnosis is a stepwise pathway starting from clinical suspicion and employing several neuroradiological techniques, mainly Computed Tomography (CT)-based and Magnetic Resonance Imaging (MRI)-based modalities. The neuroradiological findings, both in the diagnostic phase and in the follow-up phase, may provide some results at risk for misdiagnosis. Non-thrombotic filling defects of intracranial dural sinuses are among them, and the potential sources are artefactual and or anatomical (venous septa and arachnoid granulations). The misdiagnosis of these findings as CVT is potentially linked to dangerous consequences. A potential strategy to avoid this is to increase the knowledge about technical and anatomical reasons for non-thrombotic filling defects of intracranial dural sinuses and their imaging features. The main aim of this review is to address these issues, including the variability of the intracranial venous pathways, providing the solutions for overcoming the above-cited potential misdiagnosis of non-thrombotic filling defects as CVT. Full article

Background: This study aims to analyze potential risk factors that may influence the clinical outcomes following surgical treatment of traumatic peroneal nerve lesions. Methods: We conducted a retrospective analysis of patients with traumatic peroneal nerve injuries treated with decompression, split repair, or nerve grafting between 2010 and 2020. Motor function and potential risk factors were evaluated. Results: Out of 93 patients, 42 (45%) underwent decompression, 15 (16%) received split repair, and 36 (39%) required autologous nerve grafting. Up to one year after surgery, weakness of the anterior tibial muscle improved from a median of M0 to M3. After one year following nerve decompression, functional recovery was observed in 28 (65%) cases, in 9 (21%) cases after split repair, and in 7 (16%) cases following autologous nerve grafting. A defect greater than 8 cm was associated with significantly poorer improvement of extensor hallucis longus (p = 0.037, HR 0.109). We found no significant associations between age, diabetes mellitus, arterial hypertension, obesity, and postoperative outcomes. Conclusions: According to the present data, a significant number of patients achieved functional improvement following surgical treatment, indicating that this procedure should be considered an important treatment option in selected cases. Full article

Background: Endoscopic pituitary surgery might yield better endocrine outcomes compared to microscopic resection. We conducted a prospective, randomized, single-blinded study to compare the endocrine outcome and quality of life (QoL) of patients with newly diagnosed pituitary adenoma who underwent either endoscopic or microscopic transsphenoidal surgery (NCT03515603). Methods: Due to slow recruitment, this study had to be stopped prematurely. Out of 170 transsphenoidal pituitary surgeries performed during the study period, 36 patients were enrolled in this study. The primary endpoint was based on the development of a new hypopituitarism. Secondary endpoints included the extent of resection, complications, and QoL. Results: Endoscopic surgery was performed in 47.2% (n = 17). A new hypopituitarism was found in 8.3% (n = 3). All these cases underwent microscopic resection. Arginine vasopressin deficiency was found in 2.7% (n = 1) after microscopic resection. Gross total resection was achieved in 94.4% (n = 34). No surgical complications or new neurological deficits were observed. QoL improved significantly after the surgery, as measured by EQ-VAS (p = 0.003). According to EQ-5D3L, QoL improved or remained unchanged in almost all patients. No significant difference was found in QoL between the endoscopic and microscopic groups. Conclusion: The endoscopic technique appears to offer benefits in the treatment of pituitary adenomas, particularly in terms of achieving a favorable endocrine outcome. Full article

The purpose of this review is to compile and discuss available evidence in humans on the efficacy of YHM supplementation on performance in different exercise modalities. Yohimbine (YHM) is a naturally occurring alkaloid that induces increases in sympathetic nervous system (SNS) activation effectively initiating “fight or flight” responses. In supplement form, YHM is commonly sold as an isolated product or combined into multi-ingredient exercise supplements and is widely consumed in fitness settings despite the lack of empirical support until recently. YHM primarily acts as an α2-adrenergic receptor antagonist effectively increasing norepinephrine release from sympathetic neurons. YHM has been implicated in improving or altering cardiovascular function, blood flow, lactate metabolism, and muscle function. Emerging evidence has suggested that YHM may have the potential to improve performance in a wide range of exercise modes including endurance, sprint, and resistance exercise. Performance enhancement with YHM is mediated by mechanistic underpinnings of physiological and psychological alterations to exercise responses including increased sympathetic activation, adaptive hemodynamic changes, increased alertness, and decreased fatigue. However, YHM use is not without risk as it has high interindividual variability in bioavailability, can be deceptively potent, lacks widely accepted dosing recommendations, and, when taken in large doses, has been empirically documented to result in serious side effects. Despite this, the evidence presented in this review suggests low doses of YHM are tolerable and may serve as an ideal exercise training aid due to acute enhancement of physical performance. However, safety concerns remain outstanding and temperance should be used when using YHM and similar sympathomimetics. Full article

Cluster headache is a severe, poorly understood disorder for which there are as yet virtually no rationally derived treatments. Here, Lee Kudrow’s 1983 theory, that cluster headache is an overly zealous response to hypoxia, is updated according to current understandings of hypoxia detection, signaling, and sensitization. It is shown that the distinctive clinical characteristics of cluster headache (circadian timing of attacks and circannual patterning of bouts, autonomic symptoms, and agitation), risk factors (cigarette smoking; male gender), triggers (alcohol; nitroglycerin), genetic findings (GWAS studies), anatomical substrate (paraventricular nucleus of the hypothalamus, solitary tract nucleus/NTS, and trigeminal nucleus caudalis), neurochemical features (elevated levels of galectin-3, nitric oxide, tyramine, and tryptamine), and responsiveness to treatments (verapamil, lithium, melatonin, prednisone, oxygen, and histamine desensitization) can all be understood in terms of hypoxic signaling. Novel treatment directions are hypothesized, including repurposing pharmacological antagonists of hypoxic signaling molecules (HIF-2; P2X3) for cluster headache, breath training, physical exercise, high-dose thiamine, carnosine, and the flavonoid kaempferol. The limits of current knowledge are described, and a program of basic and translational research is proposed. Full article

Neurosyphilis-induced dementia represents a severe manifestation of tertiary syphilis, characterized by cognitive and neuropsychiatric impairments. This condition arises from the progression of syphilis to the central nervous system, where the spirochete causes damage through invasion, chronic inflammation, and neurodegeneration. The pathophysiology involves chronic inflammatory responses, direct bacterial damage, and proteinopathies. Treponema pallidum triggers an inflammatory cascade, resulting in neuronal injury and synaptic dysfunction. Abnormal protein accumulations, including TAR DNA-binding protein 43 (TDP-43) and tau, contribute to neuronal loss and cognitive decline. Seizures, psychiatric symptoms, and motor deficits further complicate the progression of dementia. Diagnosis includes clinical assessment, cerebrospinal fluid analysis, and neuroimaging. Diagnostic tests include CSF-VDRL, FTA-ABS, and neuroimaging techniques such as MRI and PET scans, which help detect structural changes and confirm neurosyphilis. Management of neurosyphilis-induced dementia involves antibiotic therapy and psychotropic medications to address both infectious and symptomatic components. While penicillin remains the cornerstone of treatment, psychotropic agents, including haloperidol, risperidone, quetiapine, and divalproex sodium, can manage psychiatric symptoms. However, careful monitoring is required due to potential side effects and interactions with ongoing treatment. Overall, early diagnosis and comprehensive management are crucial for mitigating the cognitive and neuropsychiatric impairments associated with neurosyphilis-induced dementia. Full article

Background and Objectives: Leprosy primarily affects peripheral nerves, leading to significant neurological complications such as polyneuritis, mononeurosis, and autonomic dysfunction, which contribute to severe disabilities and impaired quality of life for patients. This scoping review aims to investigate the neurological manifestations and main treatments of leprosy patients. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases. This review has been registered on OSF (n) PQBYH. Results: Neurological complications of leprosy, such as neuropathy and paralysis, necessitate accurate diagnosis and treatment, as immunological reactions can exacerbate nerve damage. Various studies highlight the effectiveness of personalized therapies, such as corticosteroids, multi-drug therapy (MDT), and surgical interventions, in improving symptoms and neurological function in leprosy patients. Conclusions: Managing neurological complications of leprosy necessitates careful diagnosis and treatment, as many patients experience unresolved peripheral neuropathy despite multidrug therapy. Future research should focus on improving diagnostic tools, exploring the link between neuropathic pain and psychological issues, and developing effective vaccines and treatments to enhance patient outcomes. Full article

Background: Ventriculoperitoneal (VP) shunt therapy is a crucial intervention for normal-pressure hydrocephalus (NPH). This meta-analysis delves into survival time and the impact of baseline symptom burden on survival after VP shunt therapy for NPH, employing reconstructed pooled survival curves and a one-stage meta-analysis. Methods: IPD regarding overall survival (OS) were acquired from published Kaplan–Meier charts, utilizing the R package IPDfromKM in R (Version 4.3.1, the R Foundation for Statistical Computing). Reconstructed Kaplan–Meier charts were then generated from the pooled IPD data. Both one-stage and two-stage meta-analyses were executed, with hazard ratios (HRs) employed as metrics to evaluate effectiveness. Results: From the initial screening of 216 records, five articles encompassing 1614 patients met the eligibility criteria for inclusion. In two of the five included studies, overall survival was stratified by gait score (1–4 vs. ≥4) in 1043 patients, continence score (1–3 vs. ≥4) in 1022 patients, and mRS (0–2 vs. ≥3) in 956 patients. Patients with good gait demonstrated a mean survival of 8.24 years, while those with poor gait had a mean survival of 6.19 years (log-rank test: p < 0.001). The HR for gait was 2.25 (95% CI: 1.81–2.81, p < 0.001). Continence score stratification revealed a significant difference in survival time (log-rank test: p < 0.001), with an HR of 1.66 (95% CI: 1.33–2.06, p < 0.001). Similarly, mRS stratification demonstrated a significant survival difference (log-rank test: p < 0.001), with an HR of 2.21 (95% CI: 1. 74–2.80, p < 0.001). The reconstructed survival curves for all NPH patients treated with VP shunt therapy, pooling data from five studies, revealed a median survival time of 8.82 years (95% CI: 8.23–9.40). Survival rates at 1, 3, 5, 7, 9, 11, and 13 years were 95.7%, 83.8%, 70.5%, 59.5%, 48.7%, 35.8%, and 25.4%, respectively. Comparison with a general control population showed an HR of 1.79 (95% CI: 1.62–1.98, p < 0.001). Conclusions: This comprehensive meta-analysis underscores the influence of baseline symptom burden on survival after VP shunt therapy in NPH. Therapy in the early stages for those without significant comorbidities may enhance survival. Full article

Background: The utility of single-pulse TMS (transcranial magnetic stimulation)-evoked EEG (electroencephalograph) potentials (TEPs) has been extensively studied in the past three decades. TEPs have been shown to provide insights into features of cortical excitability and connectivity, reflecting mechanisms of excitatory/inhibitory balance, in various neurological and psychiatric conditions. In the present study, we sought to review and summarize the most studied neurological and psychiatric clinical indications utilizing single-pulse TEP and describe its promise as an informative novel tool for the evaluation of brain physiology. Methods: A thorough search of PubMed, Embase, and Google Scholar for original research utilizing single-pulse TMS-EEG and the measurement of TEP was conducted. Our review focused on the indications and outcomes most clinically relevant, commonly studied, and well-supported scientifically. Results: We included a total of 55 publications and summarized them by clinical application. We categorized these publications into seven sub-sections: healthy aging, Alzheimer’s disease (AD), disorders of consciousness (DOCs), stroke rehabilitation and recovery, major depressive disorder (MDD), Parkinson’s disease (PD), as well as prediction and monitoring of treatment response. Conclusions: TEP is a useful measurement of mechanisms underlying neuronal networks. It may be utilized in several clinical applications. Its most prominent uses include monitoring of consciousness levels in DOCs, monitoring and prediction of treatment response in MDD, and diagnosis of AD. Additional applications including the monitoring of stroke rehabilitation and recovery, as well as a diagnostic aid for PD, have also shown encouraging results but require further evidence from randomized controlled trials (RCTs). Full article

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease that primarily targets the myelin of axons. Extremities are frequently affected, resulting in a negative impact on both activities of daily living (ADL) and quality of life. In recent years, there has been increasing interest in the potential benefits of exercise and blood flow restriction training (BFRT) programs as a therapeutic tool in people with neurological disorders. The aim of the present systematic review was to know the clinical effects of BFRT programs in people with MS. Methods: A systematically comprehensive literature search was conducted and registered in PROSPERO prior to its execution under the reference number CRD42024588963. The following data sources were used: Pubmed, Scopus, Web of Science (WOS) and the Cochrane Library. The following data were extracted from the papers: study design, sample, interventions, dosage, outcome measures and results. To assess the methodological quality of the papers included, the Quality Index of Downs and Black was used. Additionally, the articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. Also, the Cochrane Handbook for Systematic Reviews of Interventions was used by two independent reviewers to assess risk of bias, assessing the six different domains. Results: Seven articles with a total of 71 participants were included in the review. Of the seven articles, five papers studied the effectiveness of BFRT combined with strengthening exercises and two papers studied the effect of BFRT combined with aerobic exercise. Of the five articles that analyzed BFRT combined with strengthening exercises, only two presented a control group. Both performed a low-load resistance training in combination with BFRT with four series, 30/15/15/15 repetitions and a rest of 1 min between the series and 3 min between the exercises. The control groups to which they were compared performed a high intensity strengthening exercise protocol which had the same exercises, sets, rests and duration of the protocol as the experimental groups. For those two papers which investigated the effects of BFRT combined with aerobic training, exercise was performed in two sessions per week for a period of 8 and 6 weeks, respectively. In both studies, the experimental protocol began with a warm-up phase and ended with a cool-down phase, and there were differences in cuff management. All these investigations found positive effects in the interventions that combined exercise with BFRT. The characteristics, outcome measures, effects of the interventions and the assessment of the methodological quality of the included studies and risk of bias are shown in the tables. Conclusions: BFRT in people with MS appears to be effective and safe for people with MS. BFRT might show positive clinical effects on strength, hypertrophy and balance outcomes. Nevertheless, future research should be conducted with better methodological quality to ensure the potential benefits of BFRT in people with MS since the studies analyzed present a high risk of bias and methodological limitations. Full article

Introduction: Painful legs and moving toes (PLMT) syndrome is a rare movement disorder characterized by defuse lower limb neuropathic pain and spontaneous abnormal, involuntary toe movements. Objective: The objective was to present a rare case of PLMT syndrome with a triggering area in an adult patient due to multilevel discogenic pathology, to make a thorough review of this disorder and to provide a practical approach to its management. Case presentation: A 59-years-old male was admitted to the neurology ward with symptoms of defuse pain in the lower-back and the right leg accompanied by involuntary movements for the right toes intensified by tactile stimulation in the right upper thigh. Magnetic resonance imaging (MRI) revealed a multilevel discogenic pathology of the lumbar and cervical spine, with myelopathy at C5-C7 level. A medication with Pregabalin 300 mg/daily significantly improved both the abnormal toe movements and the leg pain. The clinical effect was constant during the 90-day follow-up without any adverse effects. Conclusion: Painful legs and moving toes (PLMT) is a condition that greatly affects the quality of life of patients, but which still remains less known by clinicians. Spontaneous resolution is rare, and oral medications are the first-line treatment. Pregabalin is a safe and effective treatment option for PLMT that should be considered early for the management of this condition. Other medication interventions, such as botulinum toxin injections, spinal blockade, or non-pharmacological treatment options like spinal cord stimulation, and surgical decompressions, are also recommended when the conservative treatment is ineffective in well-selected patients. Full article

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremors, balance impairments, and mobility limitations. Innovative approaches like combining transcranial direct current stimulation (tDCS) with exercise show promise in addressing these symptoms. This study investigates the effects of exercise combined with tDCS on mobility and tremor management in PD patients. Methods: Twenty-five individuals aged 60−75 (66.6 ± 7.33), diagnosed with PD (Hoehn and Yahr stage 2−3), were assigned to three groups in a randomized controlled design: exercise with active tDCS (n = 8), exercise with sham tDCS (n = 8), and a control group (n = 9). Dual-task training sessions focusing on walking speed, balance, and force control were conducted over ten sessions. Results: No significant differences were detected across the groups for grip strength or force control measures (p > 0.05). Significant improvements were observed in the intervention group: the Timed Up and Go (TUG) test showed a significant reduction in time (mean difference = 2.498 s, p < 0.001, ηp² = 0.331); anterior–posterior displacement significantly increased (mean difference = 21.375 mm, p = 0.0269, ηp² = 0.303); and force-tremor decoupling improved, with coherence in the 1−4 Hz band significantly decreasing (p = 0.0067). Finally, changes in TUG from post- to pre-treatment values were significantly positively correlated with the changes in coherence (R = 0.468, p = 0.018). Conclusions: Combining tDCS with exercise enhances mobility and tremor management in PD patients. These findings support the potential for such interventions to improve functional outcomes and quality of life for individuals with PD. Full article

Chronic immune sensory polyradiculopathy (CISP) is a rare inflammatory immune disorder affecting the nervous system, primarily targeting the proximal sensory nerve roots. The condition was first described by Sinreich in 2004. We conducted a systematic review of CISP cases published on PubMed to identify common clinical presentations, along with neurophysiological, radiological, cerebrospinal fluid (CSF), and other findings. Our review included a total of 22 patients from 8 articles. Many patients presented with gait difficulties and sensory ataxia and were found to have normal nerve conduction studies (NCS) and electromyography (EMG) but exhibited characteristic abnormalities in somatosensory evoked potentials (SSEP), elevated CSF protein levels, thickened nerve roots on contrast-enhanced lumbar spine MRIs, and histological changes on nerve root biopsies. Clinical improvement was observed following treatment with steroids and/or intravenous immunoglobulin (IVIG). The study concluded that while CISP is rare, it is an important clinical entity to consider, as accurate diagnosis and appropriate treatment can lead to significant improvements in neurological symptoms and disabilities. Full article

Aims: The aim of this study is to assess the sleep quality and daytime sleepiness improvement in chronic migraineurs after 6 months of a 2:1 KD (ketogenic diet) and LGID (low-glycemic-index diet). Methods: Twenty-six patients underwent 2:1 KD (11 patients) and LGID (15 patients). PSQI (Pittsburgh sleep quality index) and ESS (Epworth sleepiness scale) were administered at the baseline and the 3-month and 6-month follow-up. MIDAS (Migraine Disability Assessment), HIT-6 (Headache Impact Test 6), migraine frequency (migraine days per month), migraine intensity, BMI (Body Mass Index), FM (Fat Mass), and FFM (Fat-Free Mass) were also assessed. Results: PSQI (F_{1.544, 38.606} = 7.250; p = 0.004), ESS (F_{1.988, 49.708} = 9.938; p < 0.001), HIT-6 (F_{1.432, 35.805} = 12.693; p < 0.001), migraine frequency (F_{1.522, 38.041} = 23.070; p < 0.001), migraine intensity (F_{1.949, 48.721} = 18.798; p < 0.001), BMI (F_{1.274, 31.857} = 38.191; p < 0.001), and FM (F_{1.245, 31.134} = 45.487; p < 0.001) improved significantly. The MIDAS (F_{1.005, 25.121} = 3.037; p = 0.093) and the FMM (F_{1.311, 32.784} = 1.741; p = 0.197) did not improve significantly. The ESS (p = 0.712) and PSQI (p = 0.776) data at 3-month and 6-month follow-ups did not differ significantly, as well as for migraine frequency, migraine intensity, BMI, FM, and HIT-6. A mild correlation emerged between the mean FM and mean ESS reduction during the 6 months (r = 0.497, p = 0.010). Conclusions: Six months of LGID and 2:1 KD can improve sleep quality and daytime sleepiness in patients with chronic migraine. The effectiveness on migraine, sleep quality, and daytime sleepiness does not differ significantly between the 3-month and 6-month follow-up periods. Full article

Background/Objectives: UBL3 (Ubiquitin-like 3) is a protein that plays a crucial role in post-translational modifications, particularly in regulating protein transport within small extracellular vesicles. While previous research has predominantly focused on its interactions with α-synuclein, this study investigates UBL3’s role in Huntington’s disease (HD). HD is characterized by movement disorders and cognitive impairments, with its pathogenesis linked to toxic, polyglutamine (polyQ)-expanded mutant huntingtin fragments (mHTT). However, the mechanisms underlying the interaction between UBL3 and mHTT remain poorly understood. Methods: To elucidate this relationship, we performed hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) on postmortem brain tissue from HD patients. Gaussia princeps-based split-luciferase complementation assay and co-immunoprecipitation were employed to confirm the interaction between UBL3 and mHTT. Additionally, we conducted a HiBiT lytic detection assay to assess the influence of UBL3 on the intracellular sorting of mHTT. Finally, immunocytochemical staining was utilized to validate the colocalization and distribution of these proteins. Results: Our findings revealed UBL3-positive inclusions in the cytoplasm and nuclei of neurons throughout the striatum of HD patients. We discovered that UBL3 colocalizes and interacts with mHTT and modulates its intracellular sorting. Conclusions: These results suggest that UBL3 may play a significant role in the interaction and sorting of mHTT, contributing to the understanding of its potential implications in the pathophysiology of Huntington’s disease. Full article

Background: The lateral antebrachial cutaneous nerve (LACN) is the terminal sensory branch of the musculocutaneous nerve and is rarely entrapped or injured. This study describes the electrodiagnostic (EDX) findings and etiologies of LACN neuropathy. Methods: This is a review of 49 patients with pain and/or paresthesia of the forearm who underwent EDX studies. The diagnosis of LACN neuropathy was based on clinical and sensory conduction abnormalities. Results: The most common etiology of LACN neuropathy was iatrogenic injury in 30 (61.2%) patients, primarily due to biceps tendon repair at the elbow (11 [36.7%]) and phlebotomy (5 [16.7%]). Fifteen (30.6%) patients sustained a non-iatrogenic injury at the proximal forearm/elbow, consisting of six (60%) laceration injuries and five (33.3%) stretch injuries. Four (8.2%) patients comprised the “other” etiology category, including two mass lesions causing LACN compression. Pain, paresthesia, and/or numbness in the LACN distribution were reported in 33 (67.3%), 27 (55.1%), and 23 (46.9%) patients, respectively. Hypoesthesia was detected in 45 (91.8%) patients, and dysesthesia in 7 (14.3%). The sensory nerve action potentials (SNAPs) of the LACN on the symptomatic side were absent in 44 (89.8%) patients. Of the five patients whose SNAPs of the LACN were detected, all had a decreased amplitude, and two had increased sensory latency. Conclusions: The most common etiology for LACN neuropathy in this series was iatrogenic injury; repair of biceps tendon at the elbow was the most frequent provoking cause. Protection of the LACN during surgical procedures at the elbow and forearm is vital to prevent iatrogenic injury. Full article

Creutzfeldt-Jakob disease is a rare neurodegenerative and invariably fatal disease with a fulminant course once the first clinical symptoms emerge. Its incidence appears to be rising, although the increasing figures may be related to the improved diagnostic tools. Due to the highly variable clinical picture at onset, many specialty physicians should be aware of this disease and refer the patient to a neurologist for complete evaluation. The diagnostic criteria have been changed based on the considerable progress made in research on the pathogenesis and on the identification of reliable biomarkers. Moreover, accumulated knowledge on pathogenesis led to the identification of a series of possible therapeutic targets, although, given the low incidence and very rapid course, the evaluation of safety and efficacy of these therapeutic strategies is challenging. Full article

Diabetes mellitus-related morbidity and mortality are primarily caused by long-term complications such as retinopathy, nephropathy, cardiomyopathy, and neuropathy. Diabetic neuropathy (DN) involves the progressive degeneration of axons and nerve fibers due to chronic exposure to hyperglycemia. This metabolic disturbance leads to excessive activation of the glycolytic pathway, inducing oxidative stress and mitochondrial dysfunction, ultimately resulting in nerve damage. There is no specific treatment for painful DN, and new approaches should aim not only to relieve pain but also to prevent oxidative stress and reduce inflammation. Given that existing therapies for painful DN are not effective for diabetic patients, mesenchymal stromal cells (MSCs)-based therapy shows promise for providing immunomodulatory and paracrine regulatory functions. MSCs from various sources can improve neuronal dysfunction associated with DN. Transplantation of MSCs has led to a reduction in hyperalgesia and allodynia, along with the recovery of nerve function in diabetic rats. While the pathogenesis of diabetic neuropathic pain is complex, clinical trials have demonstrated the importance of MSCs in modulating the immune response in diabetic patients. MSCs reduce the levels of inflammatory factors and increase anti-inflammatory cytokines, thereby interfering with the progression of DM. Further investigation is necessary to ensure the safety and efficacy of MSCs in preventing or treating neuropathic pain in diabetic patients. Full article

Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile. Full article

Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes the current evidence on the epidemiology, pathophysiology, and neurological consequences of OSA in pregnancy, along with the potential management strategies. Articles were sourced from the PubMed, EMBASE, and Cochrane databases until 2023. Our comprehensive review highlights that the incidence of OSA increases during pregnancy due to physiological changes such as weight gain and hormonal fluctuations. OSA in pregnancy is linked with gestational hypertension, pre-eclampsia, gestational diabetes, and potential adverse fetal outcomes such as intrauterine growth restriction and preterm birth. Continuous positive airway pressure (CPAP) therapy remains the most effective management strategy for pregnant women with OSA. However, adherence to CPAP therapy is often suboptimal. This comprehensive review underscores the importance of the early recognition, timely diagnosis, and effective management of OSA in pregnancy to improve both maternal and fetal outcomes. Future research should focus on enhancing screening strategies and improving adherence to CPAP therapy in this population. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative condition marked by the gradual deterioration of dopaminergic neurons in the substantia nigra. Oxidative stress has been identified as a key player in the development of PD in recent studies. In the first part, we discuss the sources of oxidative stress in PD, including mitochondrial dysfunction, dopamine metabolism, and neuroinflammation. This paper delves into the possibility of mitigating oxidative stress as a potential treatment approach for PD. In addition, we examine the hurdles and potential of antioxidant therapy, including the challenge of delivering antioxidants to the brain and the requirement for biomarkers to track oxidative stress in PD patients. However, even if antioxidant therapy holds promise, further investigation is needed to determine its efficacy and safety in PD treatment. Full article

Sacral Tarlov cysts (TCs), often asymptomatic, can cause significant pain and severe neurological dysfunction. Conventional treatments are generally associated with high recurrence and complication rates. Specifically, the substantial recurrence rates, which can reach as high as 50%, significantly impact long-term outcomes. Recent evidence increasingly supports the hypothesis that the formation of Tarlov cysts (TCs) may be associated with inflammatory processes within the nerve root sheath, further exacerbated by elevated cerebrospinal fluid (CSF) pressure. This retrospective study explores thecaloscopy, combined with surgical techniques, as a more effective alternative. We observed a total of 78 patients, 48 of whom underwent endoscopic fenestration of the arachnoid sheath in addition to microsurgical resection of the TC. We found that the fenestration of the arachnoid sheath at the level of lumbosacral spinal nerve root entry led to a significantly decreased risk of developing recurrent TCs (5/48 vs. 9/30). Only one of the patients suffered from a persistent new bladder dysfunction after microsurgical resection. This presented technique provides a promising treatment path for the future management of TCs, offering a safe and more effective treatment option compared to previous methods. Additionally, the advantages of the thecaloscopy provide pathophysiological implications regarding the development of perineural cysts. Full article

Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [¹²⁵I]5-iodo-3-pyridinecarboxamido-Lecanemab ([¹²⁵I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([¹²⁵I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [¹²⁵I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [¹²⁵I]IPC-Lecanemab regional binding in the postmortem AD human brains. [¹²⁵I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [¹⁸F]flotaza and [¹²⁵I]IBETA, in the same subjects. [¹⁸F]Flotaza and [¹²⁵I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [¹²⁵I]IPC-Lecanemab. Our results suggest that radiolabeled [¹²⁵I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [¹²⁴I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions. Full article