Neurology International最新文献

Background: Neuropathic pain represents a substantial global burden with limited effective therapeutic options. Pulsed Electromagnetic Field (PEMF) therapy has emerged as a potential non-invasive adjuvant, though clinical evidence remains inconsistent. This systematic review and meta-analysis evaluated PEMF efficacy and safety, specifically analyzing the influence of etiology and stimulation parameters.

Methods: Following PRISMA 2020 guidelines (PROSPERO: CRD420251184151), five databases (Cochrane, PubMed, Scopus, Web of Science, and LILACS) were searched for Randomized Controlled Trials (RCTs) comparing PEMF versus sham. Risk of bias was assessed via Cochrane RoB 2, and heterogeneity was explored through detailed subgroup analyses.

Results: Thirteen RCTs met the inclusion criteria (N = 688). While global analysis indicated a statistically significant pain reduction (SMD: -1.01; p = 0.03), it exhibited extreme statistical heterogeneity (I² = 92.8%) and instability. After adjusting for missing studies using the Trim-and-Fill method, global significance disappeared. However, subgroup analysis resolved this inconsistency, revealing a massive, clinically meaningful effect in Spinal/Radicular pain (SMD: -2.35; 95% CI: -4.42 to -0.29), whereas Peripheral Neuropathy showed no significant reduction (SMD: -0.38; 95% CI: -0.86 to 0.10).

Conclusions: The PEMF evidence base for neuropathic pain is currently highly fragmented. Extreme heterogeneity and publication bias render "one-size-fits-all" efficacy estimates invalid and potentially misleading. Instead, our data reveals a critical etiological divergence: PEMF appears highly effective for spinal/radicular pathology, likely due to the mechanical nature of the lesion, but demonstrates limited efficacy for diffuse peripheral neuropathy. Future research must abandon generic protocols in favor of etiology-specific trials, prioritizing high-frequency parameters and rigorous bias control.

Background/objectives: Protein Z (PZ) and the protein Z-dependent protease inhibitor (ZPI) are vitamin K-dependent regulators of coagulation that inhibit activated factor Xa. Their relevance in ischemic stroke (IS) remains insufficiently characterized, with inconsistent evidence regarding their association with stroke severity and outcomes. This study aimed to evaluate the concentrations and dynamics of PZ and ZPI in the acute phase of IS in patients treated with intravenous thrombolysis or conservative therapy and to assess their potential prognostic significance.

Methods: Eighty-four patients with acute IS were enrolled and divided into two groups: group I treated with intravenous thrombolysis (rt-PA) and group II managed conservatively. PZ and ZPI concentrations were measured using ELISA on admission (day 1) and on day 7. Associations with factor X activity, the modified Rankin Scale (mRS), and the National Institutes of Health Stroke Scale (NIHSS) were analyzed using nonparametric tests and Spearman correlations (p < 0.05).

Results: PZ concentrations were significantly higher in thrombolysis-treated patients than in conservatively managed patients both on day 1 (median: 2810.05 vs. 2178.50 ng/mL; p = 0.024) and day 7 (2982.90 vs. 2286.50 ng/mL; p = 0.026). A slight negative correlation between PZ and mRS on day 7 was observed in the conservative group (r = -0.360; p = 0.043). In thrombolysis-treated patients with dyslipidemia, PZ increased from day 1 to day 7, whereas it decreased in those without dyslipidemia. No significant correlations were found between PZ, ZPI, or factor X and NIHSS or ASTRAL scores.

Conclusions: Higher PZ concentrations in the acute phase of IS-particularly in rt-PA-treated patients-may reflect differences related to the timing of the acute ischemic process and reperfusion status, suggesting potential utility as markers of stroke severity or outcome.

Background: In Parkinson's disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction studies were performed on 13 patients with multiple system atrophy (MSA) and 9 patients with progressive supranuclear palsy (PSP) at baseline. PNP was diagnosed according to standard electrophysiological criteria after exclusion of common secondary causes. Comprehensive clinical evaluation included motor and non-motor assessments over two years of follow-up. Results: At baseline, PNP was present in 53.8% of MSA patients and 66.7% of PSP patients. MSA patients with PNP showed greater motor symptom severity (UPDRS III score; p = 0.046) and worse cognitive performance (MoCA; p = 0.044) compared to those without PNP. Over two years, a significant reduction in the tibial nerve amplitude was observed exclusively in MSA patients (p = 0.039), paralleling disease progression. Conclusions: This study provides the first longitudinal evaluation of clinical and electrophysiological PNP progression in MSA and PSP. A high comorbidity of PNP in patients with APS could contribute to motor and sensory impairments in these patients. Our findings indicate that PNP progression may reflect disease progression in MSA. Given the limited sample size, larger-scale longitudinal studies are needed to further investigate biomarker potential of PNP in APS and to clarify differences in peripheral nerve involvement between synucleinopathies and tauopathies.

Background: Parkinson's disease (PD) is characterized by motor disturbances that significantly impact balance, gait, and quality of life. Personalized Rhythmic Auditory Stimulation (pRAS) is an emerging rehabilitative approach that utilizes auditory entrainment to improve step and gait control. The aim of this systematic review is to critically summarize the data from the most recent evidence concerning the use of pRAS in gait rehabilitation for patients with Parkinson's disease. Methods: A systematic review was conducted following PRISMA guidelines, including records that evaluated music-based or technological interventions based on personalized RAS. Primary outcomes included spatiotemporal gait parameters and distance covered. Results: Ten studies were included in the analysis. All the studies reported clinically relevant improvements: increases in gait speed, step length, and amplitude. Moreover, a reduction in freezing of gait episodes (up to 36%), greater walking distance, and good adherence were reported. Conclusions: Personalized, adaptive, or on-demand solutions proved more effective than traditional forms of cueing. Moreover, the available evidence suggests that pRAS constitutes an effective and safe rehabilitative option for gait disturbances in PD. However, further studies with larger sample sizes and prolonged follow-up periods are necessary to evaluate its long-term impact and transferability into clinical practice.

Background: Environmental factors are known to influence the clinical presentation of patients with multiple sclerosis. This study aims to compare the demographic and clinical characteristics of multiple sclerosis patients treated at two diverse geographical settings. Methods: A cross-sectional, observational cohort study was conducted in two MS centers: the Danish Multiple Sclerosis Center (DMSC) in Copenhagen, Denmark and the Regional MS Center in Târgu Mureș, Romania. We compared patients' demographic and clinical characteristics between MS centers, including sex distribution, current age, MS onset age, latest EDSS scores, symptomatology at disease onset, MS phenotype and type of ongoing DMT. Results: In both cohorts, sex distribution was similar, with females constituting 69.2% in DMSC, and 65.7% in Târgu Mureș. Pyramidal symptoms at MS onset were predominant among Targu Mures patients (32.7%), while sensory symptoms were more frequent among DMSC patients (33%). Progressive forms of MS were more prevalent in Târgu Mureș (22.6%) compared to DMSC (9.9%). High-efficacy DMTs were on use by 58.3% patients in DMSC and only by 29.4% patients in Târgu Mureș, who were mostly on low-efficacy DMTs (54.4% vs. 12.4% in DMSC). Conclusions: The study highlights both shared and distinct characteristics of MS patients treated in these two centers. These findings underscore the importance of regional considerations in the management and treatment of MS.

Background: Neonatal hypoxic-ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and ketone bodies have emerged as potential adjunctive neuroprotective interventions. This scoping review aims to critically evaluate the mechanistic rationale, preclinical evidence, and clinical feasibility of ketogenic approaches.

Methods: A scoping review of the literature was conducted, including experimental and clinical studies investigating ketogenic diets, endogenous ketosis, and exogenous ketone supplementation in neonatal hypoxia-ischemia. Evidence was synthesized across mechanistic, preclinical, nutritional, and clinical domains, with particular attention to developmental context, timing of intervention, safety considerations, and translational relevance in the contest of therapeutic hypothermia.

Results: Preclinical studies consistently demonstrate that ketone bodies enhance cerebral energy metabolism, support mitochondrial function, reduce excitotoxic signaling, and attenuate oxidative stress and neuroinflammation in the immature brain. Neonatal models show preferential utilization of β-hydroxybutyrate over glucose during hypoxic-ischemic stress, suggesting intrinsic metabolic advantages. Emerging evidence also supports potential long-term effects on epigenetic regulation and white matter development, although direct causal validation in neonatal HIE remains limited. Nutritional studies indicate that carefully monitored enteral and parenteral feeding is feasible in critically ill neonates, identifying a potential window for metabolic interventions.

Conclusions: Ketogenic strategies represent a plausible, multimodal approach to targeting the metabolic and inflammatory sequelae of neonatal HIE. While current evidence is insufficient to support clinical implementation, this scoping review provides a hypothesis-generating framework to guide future translational research and the design of carefully controlled clinical trials in neonatal neurocritical care.

Parkinson's disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, frequently associated with visual and oculomotor disturbances. Quantitative analysis of eye movements represents a non-invasive method for assessing central nervous system dysfunction beyond conventional imaging; however, the diagnostic and predictive value of oculomotor metrics remains insufficiently defined. Objectives: The aims of this study were to compare smooth pursuit gain and reflexive saccade parameters (latency, velocity, and precision) between individuals with MS and healthy controls, and to evaluate their ability to discriminate disease status. Methods: This cross-sectional study included 46 clinically stable patients with MS (EDSS ≤ 6.5) and 46 age- and sex-matched healthy controls. Oculomotor function was assessed using videonystagmography under standardized conditions. Group differences across horizontal and vertical gaze directions were analyzed using linear mixed-effects models. Random forest models were applied to assess the discriminative performance of oculomotor parameters, with permutation-based feature importance and receiver operating characteristic (ROC) curve analysis. Results: Patients with MS showed significantly reduced smooth pursuit gain across most horizontal and vertical directions compared with controls. Saccadic latency was significantly prolonged in all tested movement directions. Saccadic velocity exhibited selective directional impairment consistent with subtle medial longitudinal fasciculus involvement, whereas saccadic precision did not differ significantly between groups. A random forest model combining pursuit and saccadic parameters demonstrated only moderate discriminative performance between MS patients and controls (AUC = 0.694), with saccadic latency contributing most strongly to classification. Conclusions: Quantitative eye-movement assessment revealed widespread oculomotor abnormalities in MS, particularly reduced smooth pursuit gain and prolonged saccadic latency. Although the overall discriminative accuracy of oculomotor parameters was limited, these findings support their potential role as complementary markers of central nervous system dysfunction. Further longitudinal and multimodal studies are required to clarify their clinical relevance and prognostic value.

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated with deep brain stimulation, although this remains an experimental treatment.

Methods: In this two-case report we present the first two cases of patients with Gilles de la Tourette syndrome in Slovenia treated with deep brain stimulation of the anteromedial globus pallidus internus.

Results: Over an 18-month follow-up period, we observed an improvement in both cases. In the first case, the Yale Global Tic Severity Scale score decreased from 71 (17 for motor tics, 14 for phonic tics, and 40 on the impairment scale) to 44 points (12 motor, 12 phonic, and 20 impairment). In the second case, the score decreased from 72 (16 motor, 16 phonic, and 40 impairment) to 38 points (8 motor, 10 phonic, and 20 impairment).

Conclusions: Deep brain stimulation could be a promising treatment for this disorder. However, further research is needed to determine the most suitable patients and targets.

Background: The management of spontaneous intracerebral hemorrhage (ICH) has centered around controlling blood pressure in order to prevent hematoma expansion (HE). Rate-pressure product (RPP) has emerged as a hemodynamic marker that accounts for heart rate (HR) and systolic blood pressure (SBP), both of which are crucial in modifying shear stress to the vasculature. We hypothesized that RPP in the pre-hospital hyperacute phase is positively associated with initial hematoma volume and HE. Methods: We analyzed 263 patients with primary ICH from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study with initial and interval neuroimaging. RPP was calculated as the product of HR and SBP in pre-hospital and pre-treatment phases, stratified into quintiles. HE was defined by volume expansion of >6 mL or >33% from baseline volume on repeat neuroimaging performed within 48 h of the first scan. The primary outcome was the initial hematoma volume by quintiles of hyperacute RPP. The secondary outcome was the occurrence of HE across RPP quintiles. Multivariable logistic regression was used to assess the degree to which RPP affects HE. Results: Of the 263 patients analyzed, 116 (44%) had HE. The proportion of patients with HE or the initial hematoma volume was not statistically significant across RPP quintiles overall. HE was significantly more common in female patients or patients on anticoagulation. Conclusions: Elevated RPP was not associated with increased initial hematoma volume or subsequent HE in the hyperacute period after spontaneous ICH. Future research is necessary to determine the clinical importance of RPP as a biomarker in the clinical outcome of ICH.