Neurol. Int., Volume 17, Issue 4 (April 2025) – 16 articles

Background/Objectives: Burning mouth syndrome (BMS) is a chronic pain disorder of the oral cavity in the absence of organic disease and is prevalent among menopausal women. Estrogen may be involved in the formation of nerves involved in pain. Methods: This paper presents an inferred mechanism for the relationship between estrogen and BMS based on a synthesis and interpretation of findings from a selection of published studies. Results: Estrogen influences the formation of neural circuits in BMS by dividing the complex pain circuit into the following three components: the peripheral pain circuit, brain network pain circuit, and memorized pain circuit. Conclusions: The development of BMS may be influenced by the formation of neural circuits by sex hormones. Full article

Background/Objectives: The optimal timing of rehabilitation after acute ischemic stroke is unclear. We studied neurological outcomes and safety of early mobilization (EM) within 24 h for patients receiving intravenous thrombolysis. Methods: This was a retrospective analysis of patients treated at a single Comprehensive Stroke Center from 6/2020–10/2024 with EM versus usual care. Patients were eligible for EM if they were treated with intravenous thrombolysis and had post-treatment National Institutes of Health Stroke Scale scores ≤ 5, and later, ≤10. Ordinal regression was performed to determine factors associated with a 90-day functional outcome benefit in the full cohort. Propensity scores were calculated for matched sample pairs to determine any shift towards better outcomes with EM. Results: Groups of 165 and 73 patients were treated with EM and usual care, respectively. Treatment with EM was not associated with improved 90-day neurological outcome (odds ratio [OR] for higher mRS 0.746, p = 0.265). The groups also had comparable rates of symptomatic intracranial hemorrhage, length of stay, and discharge disposition. In the propensity score analysis of 73 matched pairs, EM was comparable to usual care with respect to 90-day functional outcome (OR for higher mRS 0.891, p = 0.7). Conclusions: Mobilization within 24 h resulted in comparable rates of 90-day neurological function, symptomatic intracranial hemorrhage, and hospital length of stay in patients with mild ischemic stroke treated with intravenous thrombolysis. Future trials may further investigate the safety and efficacy of EM in alternate and larger patient cohorts. Full article

Background and purpose: Perforator stroke (PS) is a subtype of perinatal arterial ischemic stroke (PAIS), in which injuries occur in the territory of the perforator branches of the main cerebral arteries. This study aims to explore the incidence, timing, risk factors, and clinical presentation of PS in both preterm and full-term neonates. Material and methods: We retrospectively analyzed data about all the neonatal brain MRIs carried out in our hospital from March 2012 to March 2023. Criterium of inclusion was the radiologically confirmed diagnosis of perforator stroke involving one or more arterial districts. Results: A total of 1928 patients underwent brain MRIs during the period considered. PAIS was present in 50 patients, of which 19 had PS (38%). Among the patients with PS, nine were preterm babies (47%), and six suffered from perinatal asphyxia (31.5%). PS cUS diagnosis preceded MRI diagnosis in 88% of preterm babies. The mean age at cUS diagnosis was 20 ± 7 days. Preterm babies were often asymptomatic, whereas term babies showed neurological symptoms (mainly seizures). The outcome was favorable as long as PS was isolated. Conclusions: PS is surprisingly frequent among PAIS. It represents the most common form of PAIS in preterm babies and in babies suffering from birth asphyxia. Prenatal and perinatal factors suggesting a possible thromboembolic etiology leading to PAIS are rare in our population of preterm babies, in which the diagnosis was always preceded by negative cUS. These assumptions suggest a postnatal development of PS in premature babies more than a perinatal one. Full article

Background: Working memory (WM) impairment is a potential consequence of motor aphasia resulting from left-hemisphere ischemic stroke. While verbal WM has been studied extensively in this disorder, research regarding non-verbal modalities remains limited, particularly visuospatial WM, tactile WM, and the relationship between them. Additionally, language impairments limit the ability to assess WM in aphasia patients, highlighting the necessity of non-verbal diagnostic tools in clinical practice. The current study’s objectives were to compare tactile and visuospatial WM in patients with post-stroke motor aphasia and to validate the one-hand version of the Tactual Span task as a clinical measure of WM. Methods: A total of 29 participants—14 with post-stroke motor aphasia and 15 healthy controls—completed a battery of cognitive tests, including the Raven’s Colored Progressive Matrices Test, the Visuospatial Span, the Tactual Span, and a visual 1-Back task. Results: There was significantly lower performance across all WM tasks in the aphasia group compared to the controls. Additionally, the Tactual Span successfully discriminated between patients and controls, showing sensitivity estimates of 92.9% and a specificity of 66.7%, with a cut-off score of 4.5 (AUC = 0.91), for the forward stage. The backward stage revealed a sensitivity of 71.4% and a specificity of 73.3%, with a cut-off score of 3.5 (AUC = 0.83). Conclusions: The findings may suggest that non-verbal WM impairment in post-stroke aphasia affects both visuospatial and tactile modalities similarly. Furthermore, the Tactual Span appears to be sensitive to left-hemisphere stroke damage, suggesting its potential utility as a clinical tool for WM assessment in patients with motor aphasia. Full article

Background: Severe spinal cord injury (SCI) represents a debilitating condition with long-term physical and socioeconomic impacts. Understanding the pathophysiology of SCI and therapeutic interventions such as decompressive laminectomy and expansive duraplasty is crucial for optimizing patient outcomes. Objective: This systematic review explores the pathophysiology of SCI and evaluates evidence linking decompressive laminectomy and duraplasty to improved neuroplasticity and recovery. Methods: A comprehensive search was conducted in PubMed, Web of Science, and Cochrane Library for studies on decompressive surgery in SCI. Inclusion criteria were original articles investigating pathophysiology, neuroplasticity mechanisms, or surgical outcomes. Data on pathophysiological changes, molecular markers, and functional outcomes were extracted. Results: From 1240 initial articles, 43 studies were included, encompassing both animal models and human clinical data. Findings highlighted the role of inflammatory cascades, blood–spinal cord barrier disruption, and neurotrophic factor modulation in recovery. Decompressive duraplasty was associated with improved intrathecal pressure (ITP) management and neuroplasticity markers, such as BDNF and GAP-43. Conclusions: This review underscores the therapeutic potential of decompressive laminectomy and duraplasty in SCI. While evidence suggests benefits in promoting neuroplasticity, further research is needed to elucidate molecular mechanisms and refine interventions. Full article

Neurofilament light chain (NfL), an abundant cytoskeletal protein in neurons, has emerged as a promising serum biomarker that indicates non-specific neuronal damage secondary to various neurologic diseases, including multiple sclerosis (MS). Emerging evidence suggests that serum NfL levels correlate with future disability, brain atrophy, predict new disease activity, and decrease in response to various disease-modifying therapies. As research continues to validate NfL’s potential role in clinical practice, the need for a practical model to conceptualize and visualize its relevance to MS pathology becomes evident—not only for healthcare providers but also for patients. To address this, we propose the Neurofoundational Model (NFM), which likens a neuron to a home, with various parts of the home representing distinct regions of the central nervous system (CNS). In this model, the home (neuron) experiences scenarios such as a fire, an earthquake, and a slow flood, representing distinct MS disease states. A fire illustrates an MS relapse with good recovery, where serum NfL levels rise during the relapse and subsequently return near baseline. An earthquake represents an MS relapse with poor recovery, where NfL levels increase and remain elevated above baseline. Finally, a slow flood depicts MS in progressive stages, characterized by sustained and gradually increasing serum NfL levels without abrupt clinical changes. This approach offers a clear and relatable visualization for clinicians and patients alike, illustrating the dynamics of serum NfL levels during CNS damage caused by demyelination. By integrating this model into clinical practice, we aim to enhance understanding and communication regarding the role of NfL in MS pathology and its potential utility as a biomarker. Full article

Background/Objectives: Ischemic stroke remains a leading cause of death and disability worldwide. Despite significant progress in reperfusion therapy, the optimal ischemic stroke management strategy has not been developed. Recent studies demonstrate that microRNA may play an essential role in the pathophysiology of ischemic stroke and its possible potential to be a treatment target point. The proposed systematic review aimed to report the relationship between IS’s clinical severity and miRNA expression. Secondary outcomes included infarct volume, systemic inflammatory markers, and prognosis, as well as additional features such as stroke subtype, comorbidity, and risk of subsequent stroke in correlation to miRNA expression. Methods: We have performed a systematic search of database resources according to PRISMA statement guidelines. Twenty-seven studies on a total number of 3906 patients were assessed as suitable for the present SR. Included studies analyzed the expression of 30 different miRNA fragments. Results: After investigating available data, we have identified a set of possible miRNA fragment candidates that may be used in stroke diagnostics and have the potential to be a base for the development of future treatment protocols. Conclusions: Studies included in the presented SR indicate that miRNA expression may be significantly associated with clinical severity, infarct volume, and inflammation in ischemic stroke. More prospective, properly designed protocols with consistent methods of miRNA testing and optimized clinical assessment are needed to confirm the role of miRNA expression in the course of a stroke. Full article

Background/Objectives: Radiation therapy can often lead to structural and functional changes in the brain resulting in radiation-induced brain injury. This study investigates the MRI-detectable effects of whole-brain irradiation across all neuroanatomical structures in adult mice, with a specific focus on T2* MRI measurements, to evaluate regions that may be particularly sensitive to iron accumulation. Methods: One year following irradiation or sham treatment, mice were imaged with a 7T MRI to evaluate changes in regional volume and T2* relaxation times across more than 652 neuroanatomical using the DSURQE mouse brain atlas. Results: Statistical analysis identified 301 altered regions with respect to regional volume and 85 regions with respect to T2* relaxation showing significant differences relative to the control group (p < 0.05). Further data refinement, including the consolidation of redundant, bi-lateral structures revealed 18 subregions with significant changes in both volume and T2*. The data refinement revealed that the most represented system was the olfactory system (8/18 regions, 44%). The olfactory regions also showed the most pronounced changes and greatest correlation between the two metrics. Conclusions: These findings are suggestive that ionizing radiation may cause a pronounced disruption in the olfactory system that coincides with potential iron accumulation. Full article

Objective: Temporal lobe epilepsy (TLE) constitutes the most common drug-refractory epilepsy syndrome. Tailored approaches are required, as TLE originates from extrahippocampal lesions in about one-quarter of surgical candidates. Despite high success rates in seizure control, concern persists regarding postoperative memory decline after lesionectomy. We investigated the associations between structural connectivity and postoperative memory performance in extrahippocampal TLE surgery. Methods: In total, 55 patients (25 females, 30 males; mean age 29.8 ± 14.5 years; epilepsy duration 7.9 ± 10.5 years, 31 left, 24 right TLE) with extrahippocampal TLE undergoing hippocampal-sparing surgery were evaluated with standardized pre- and postoperative neuropsychological testing. Lesion volumes intersected with Human Connectome Project-derived tractography data were employed to assess the structural connectivity integrity via voxel-based and connectome-informed lesion–symptom mapping to identify cortical and white matter structures associated with cognitive outcomes. Results: Post-surgery, the widespread structural disconnection of several major white matter pathways was found, correlating with verbal memory and delayed recall. Additionally, the structural disconnection of the ipsilateral temporal lobe white matter was further associated with hippocampal atrophy. Conclusions: Our study highlights the role of structural connectivity alterations in postoperative memory decline in extrahippocampal TLE surgery. These findings expand the traditional understanding of hippocampal integrity in memory function towards the importance of broader structural networks. Individualized, connectome-informed surgical approaches might protect neurocognitive function. Full article

Background and purpose: This study aimed to investigate risk factors, prodromal signs, and non-motor symptoms (NMSs) across various motor subtypes of Parkinson’s disease (PD) and to interpret the findings within the context of existing hypotheses on PD subtypes. Methods: A search of the database yielded 300 individuals who satisfied the study’s inclusion and exclusion criteria. Among them, 168 patients diagnosed with idiopathic PD underwent a comprehensive evaluation of both motor and non-motor symptoms. The classification of motor subtypes was conducted according to the methodology proposed by Stebbins. Results: The study population consisted of 59.9% males, with an average age of disease onset at 65.45 years. Among them, 87 (51.8%) were classified as having the tremor-dominant (TD) subtype, 61 (36.3%) had the postural instability and gait disorder (PIGD) subtype, and 20 (11.9%) fell into the intermediate (I) subtype. Significant differences between motor subtypes were observed in age at assessment (p = 0.03), age at onset (p = 0.02), education level (p = 0.015), handedness (p = 0.013), proportion of non-smokers (p = 0.021), cognitive impairment (p = 0.003), and apathy (p = 0.003). Additionally, statistically significant variations were found across different rating scales and questionnaires, including MoCA (p = 0.009), HAM-A (p = 0.008), HAM-D (p = 0.007), H&Y (p = 0.004), SAS (p = 0.004), NMSS Domain 3 (mood/apathy) (p = 0.003), and NMSS Domain 5 (attention/memory) (p = 0.003). Conclusions: The study revealed substantial differences between motor subtypes, underscoring the complexity of PD. These findings highlight the importance of comprehensive evaluations of both MS and NMSs to optimize patient care, improve quality of life, and fit well within the framework of the existing hypotheses of PD subtypes. Full article

Background/Objectives: Headache is one of the most common neurological symptoms associated with COVID-19, affecting approximately 25% of patients. While most headaches resolve within weeks, some persist for months, suggesting underlying structural brain changes. This study aimed to identify brain MRI abnormalities associated with chronic headaches in patients with a history of COVID-19 infection. Methods: This retrospective study included 30 patients with post-COVID-19 headaches and 30 control patients with no history of COVID-19. Demographic characteristics were analyzed using t-tests and chi-square tests. MRI findings were categorized into six types: cortical atrophy, white matter lesions, vascular lesions, lacunar lesions, vascular encephalopathy, and sinusitis. Differences in MRI findings between the two groups were evaluated using chi-square tests. Secondary outcomes included the analysis of symptoms accompanying headaches, diagnoses following MRI, and treatments applied. Results: White matter lesions were significantly more frequent in the post-COVID-19 group (50%) compared to controls (20%) (p = 0.015). Conversely, sinusitis was more prevalent in the control group (36.7%) than in the post-COVID-19 group (6.7%) (p = 0.005). Other MRI abnormalities showed no significant differences. Cognitive dysfunction (30%) and dizziness (33.3%) were the most common associated symptoms. The most frequent diagnoses after MRI in the post-COVID-19 group were headaches/migraines (23.3%), post-COVID-19 headache (20%), and vestibular syndrome (13.3%). Conclusions: Persistent post-COVID-19 headaches may be linked to structural white matter changes observed in MRI. Further research, ideally including pre-infection imaging data, is needed to determine the causal relationship between these lesions and chronic headache symptoms. Trial Registration: This study was registered in ClinicalTrials with the trial registration number NCT06825741 on 13 February 2025. Full article

Background/Objectives: In neurocritical care, usually, the only continuous measurement of brain pathophysiology is intracranial pressure (ICP). The objective of this study was to find the relationship between cerebral blood flow (CBF) and parameters usually measured in neurocritical care, mainly central venous pressure and ICP. Methods: If the venous outflow of the CBF is considered, the CBF is controlled only by two parameters, the rICP (the ICP minus the venous blood pressure in the venous sinus at its outflow) and the Rv (the flow resistance of the soft-walled veins). For the rICP, the sinus blood pressure can be calculated from the central venous pressure (measured at the same horizontal level as the ICP) and the cervical venous flow resistance. For the Rv, the systolic ICP increase indicates the systolic arterial inflow volume, which then flows out before the diastole. The mean ICP increase divided by the mean outflow of the increased blood volume gives the Rv. This method of calculating the CBF by dividing the rICP by the Rv was named CBF(1). For validation of CBF(1), data from nine subjects in an open study were used. The data were ICP and MR blood flow measurements of arterial inflow and jugular vein outflow. Since the rICP, Rv, and CBF were unknown, an iterative method was needed to calculate these parameters. Results: The observed Rv and rICP values showed a close correlation, which indicated that CBF was dependant on the rICP only. Consequently, the comparison between the data in the study of the nine subjects, and the calculated values from CBF(1), boiled down to a comparison between the supine ICP values and the calculated rICP. The comparison showed that the rICP and supine ICP had highly significant similarity, and that the CBF(1) method was validated. Conclusions: A method for CBF measurement from ICP data in neurocritical care was found. 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: 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

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