Neurology International最新文献

Background: Transcranial pulse stimulation (TPS) is an innovative non-invasive brain stimulation technique using ultrasonic waves. Despite its application in first clinical trials, so far, no systematic overview of its effects across different patient populations has been conducted.

Objectives: This systematic review and meta-analysis examines the effects of TPS on cognitive, motor, and mental health outcomes as well as on patient safety in neurological and psychiatric disorders.

Methods: We conducted a literature search in MEDLINE, PsycINFO & PsycArticles, CENTRAL, Web of Science, and Google Scholar, covering the period from January 2013 to December 2024. Two independent reviewers conducted the study selection, data extraction, and quality assessment. To evaluate the risk of bias, the RoB2 tool was used for randomized studies and the ROBINS-I tool for non-randomized studies.

Results: A total of fifteen studies (five randomized controlled trials and ten non-blinded, single-arm trials) including both adolescent and adult and elderly patient populations (Alzheimer's disease, mild cognitive impairment, Parkinson's disease, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder) were included. Positive effects of TPS intervention on cognitive, motor, and mental health outcomes, as well as a high safety profile, were demonstrated in a majority of the studies and outcome parameters. However, limitations of the included studies persist due to small sample sizes, lack of control groups, retrospective analyses, and heterogeneity of study protocols and measurements.

Conclusions: TPS is a safe and promising method for treating neurological and psychiatric disorders. To better assess the potential of this innovative technique, standardized protocol procedures and larger, sham-controlled trials are needed.

Objectives: The application of well-controlled, quantitative measurement systems has challenged the traditional notion that rigidity in Parkinson's disease (PD) is a velocity-independent phenomenon. This review aimed to evaluate whether rigidity in PD is velocity-dependent or velocity-independent across different joints, body regions, testing speeds, and methodologies. Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of cross-sectional studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), and reporting completeness was evaluated with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: Seventeen studies were included and analyzed by the body part assessed (wrist, elbow, hand, knee, trunk). Rigidity quantification in PD used various biomechanical technologies, sometimes combined with neurophysiological methods. Although rigidity is classically considered velocity-independent, experimental evidence suggests a more complex behavior, partially velocity-dependent, especially at moderate to high angular velocities. Methodological quality was variable but generally acceptable, with more recent studies showing stronger adherence to AXIS. However, compliance with STROBE reporting standards remained inconsistent. Conclusions: While rigidity in PD has not been classically defined as velocity-dependent, current evidence indicates that, under specific testing conditions, rigidity increases with passive movement velocity. These findings challenge traditional clinical assumptions and emphasize the need for standardized measurement protocols.

Background/objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically characterized by impaired social communication. Previous reports have postulated gut microbiota to be an important non-genetic factor affecting ASD-like phenotypes in mice, as germ-free (GF) mice show impaired social communication.

Results: In this study, we identified hippuric acid (HA) as a metabolite generated via a gut microbiome-dependent mechanism that plays a role in the acquisition of social behavior during mouse development. We discovered that oral or intraperitoneal HA administration to GF mice normalizes their social behavior. Furthermore, HA administration restored oxytocin expression in the hypothalamic paraventricular nucleus and secretin expression in the subfornical organ, suggesting that HA may activate the secretin-oxytocin system to influence the social behavior of mice.

Conclusions: These findings indicate that HA may serve as an important gut microbiome-dependent mediator affecting the brain mechanisms involved in regulating social behavior.

Background/Objectives: Optic neuropathies (ON) are a clinically heterogeneous group of disorders that can cause profound and lasting visual disability, with wide-ranging effects on patients' quality of life. Although the NEI-VFQ-25 is an instrument for assessing vision-related quality of life (VRQoL), few studies have systematically compared patient-reported outcomes across multiple ON subtypes, especially in underrepresented populations. We aimed to delineate how etiological differences and longitudinal visual acuity trajectories shape VRQoL in a diverse Portuguese cohort with ON. Methods: This retrospective, cross-sectional study included 152 patients diagnosed with ON and followed at São João University Hospital, Portugal. All participants completed the validated NEI-VFQ-25. Diagnosis-specific differences in VRQoL were interrogated using ANCOVA and linear mixed-effects models, controlling for age and sex. Visual acuity changes over time were analyzed in relation to patient-reported outcomes. Results: Substantial heterogeneity in VRQoL was observed across ON subtypes. Patients with MS-related ON (MS-RON) and idiopathic ON reported significantly higher NEI-VFQ-25 scores in domains such as general vision, mental health, and dependency (F = 3.30, p = 0.013; ηp² = 0.08), while those with ischemic or other inflammatory etiologies showed persistently lower scores. Notably, both final visual acuity and diagnosis were independently associated with NEI-VFQ-25 composite scores, highlighting the correlation between objective and subjective measures of visual function. Age and diagnosis independently predicted poorer VRQoL. Conclusions: This study provides the first comprehensive evaluation of vision-related quality of life (VRQoL) across a diverse cohort of optic neuropathy patients in a Portuguese tertiary center, using the NEI-VFQ-25. Our results underscore the heterogeneity of functional impact across ON subtypes, emphasizing the value of integrating sensitive, multidimensional assessment tools into neuro-ophthalmic clinical care, especially in populations historically underrepresented in research.

Background: Long-term management of cerebral venous thrombosis (CVT) with rivaroxaban is still under evaluation. The primary objective was to compare the contemporary evidence of the safety and efficacy of rivaroxaban versus warfarin in the long-term (≥ 6 months) treatment of CVT. Methods: We searched electronic databases up to 30 April 2025 for randomised control trials (RCTs) and observational studies in CVT management. We utilised the Mantel-Haenszel (M-H) method with a fixed-effects model to calculate risk differences (RDs) between rivaroxaban and warfarin arms. The ROB 2.0 and ROBINS-I tools were used to observe the risk of bias among included studies. Results: A total of 12 studies were identified (4 RCTs and 8 observational cohorts), evaluating 1174 patients treated with rivaroxaban (n = 262) or warfarin (n = 912). The rate of recurrence of venous thrombosis was 4% lower among rivaroxaban- compared to warfarin-treated patients (1.5% vs. 4.0%; RD = -0.04; p = 0.04). However, non-recanalisation events were identical among rivaroxaban and warfarin arms (16.4% vs. 16.5%; RD = -0.01, p = 0.68). Additionally, long-term all-cause mortality (p = 0.39), clinically relevant bleeding events (p = 0.18), new intracranial haemorrhage (p = 0.79), and good clinical outcome (p = 0.92) events were similar between rivaroxaban and warfarin arms. While RCTs and observational cohorts have methodological concerns and potential bias, we validated our results by excluding studies with serious or critical risks of bias to ensure the robustness of our findings. Conclusions: Compared to warfarin, rivaroxaban offers lower recurrence rates with similar efficacy and safety profiles along with improved clinical convenience.

Background and objectives: The dopamine D2 receptor (DRD2) plays a central role in fronto-striatal circuits regulating cognitive control and reward processing. The rs1076560 polymorphism alters receptor isoform expression, potentially modifying impulsivity and vulnerability to stimulant use disorders. We examined gene-environment interactions between rs1076560 and stimulant dependence in relation to impulsivity, ADHD traits, and hedonic capacity.

Methods: A total of 517 men (235 stimulant-dependent, 282 controls) completed the Barratt Impulsiveness Scale (BIS-11), Adult ADHD Self-Report Scale (ASRS v1.1), and Snaith-Hamilton Pleasure Scale (SHAPS). Genotyping for rs1076560 was performed using real-time PCR, and two-way ANOVAs tested genotype-by-group effects.

Results: Significant genotype-by-group interactions were observed across all BIS-11 subscales and ASRS scores. In the stimulant-dependent group, C/C homozygotes showed the highest levels of attentional impulsivity and attentional dysregulation compared to both A/C and C/C controls. In contrast, within the control group, A/A homozygotes demonstrated higher motor impulsivity, non-planning impulsivity, and BIS-11 total scores than C/C controls. No significant main effects or interactions were found for SHAPS scores.

Conclusions: DRD2 rs1076560 moderates impulsivity-related traits through dopaminergic pathways relevant to executive dysfunction in stimulant use disorders. These findings highlight a neurobiological mechanism of addiction vulnerability and may inform precision approaches in neurology and psychiatry.

Background/Objectives: Cerebral small vessel disease (cSVD) and vascular cognitive impairment (VCI) are major contributors to stroke and dementia. Despite their importance, there are few effective treatments for cSVD and VCI. Variability in cSVD/VCI populations, intervention targets, and outcome selection may contribute to inconsistencies and challenges in clinical trial design. We reviewed the design of cSVD and VCI clinical trials to describe current practice in the selection of populations, interventions, and outcomes. Methods: We systematically searched Ovid Medline, Embase, and PsychInfo databases for recently completed cSVD/VCI trials and searched online trial registries (ClinicalTrials.gov, European Union Clinical Trials Register, and International Clinical Trials Registry Platform) for ongoing cSVD/VCI trials. We determined the use of specific categories of inclusion and exclusion criteria, interventions, and outcomes in the included trials and described these as counts and percentages. Results: We included a total of 82 cSVD trials and 120 VCI trials. Neuroimaging features were most frequently used as inclusion criteria for cSVD (88%) and cognition for VCI (88%). There was substantial variation in eligible ages for participation. Both cSVD and VCI trials largely excluded patients with comorbidities, vascular risk factors, and neuropsychiatric disorders, with a notable proportion of cSVD trials excluding on the basis of functional impairment. The most studied intervention classes were repurposed cardiovascular drugs (40%) for cSVD and Traditional Chinese Medicine (35%) in VCI. The most common primary outcome category was neuroimaging for cSVD (53%) and cognition for VCI (86%). Notably, functional outcomes were underused in both cSVD and VCI trials (13% and 12%, respectively, for primary outcomes). Conclusions: We have identified substantial variability in all aspects of cSVD and VCI clinical trial design. Inconsistent neuroimaging criteria and exclusions based on common long-term conditions limit the generalisability of findings. There is a need for greater focus on clinical outcomes, particularly functional ability, to better reflect treatment impact. Increased integration and standardisation of cSVD and VCI trial design is needed to accelerate progress in developing treatments.

Background: Aβ1-42 and APOE concentrations, as well as Aβ42/40 ratio, may be considered as a link between hypertension (HTN) or diabetes mellitus (DM), brain amyloidosis, and dementia. HTN and DM are associated with cognitive impairment and may contribute to the development of Alzheimer's disease (AD). This preliminary study aimed to evaluate the impact of vascular risk factors on the concentration of biochemical AD markers and cognitive state. As it is a cross-sectional study in nature, causal relationships cannot be established. Methods: The study was conducted in the south of Poland among a rural population over 65 years of age. A total of 58 patients qualified into the study were divided into groups according to the presence of HTN (n = 18) or HTN coexisting with DM (n = 40). A healthy control group was also formed (n = 20), resulting in 78 study participants. The study population was also divided based on M-ACE results, forming a normal cognition group (NC) and a deteriorated cognition group (DC). Biochemical tests, neurological scales assessments, and ultrasound examinations were conducted. Results: Patients who scored in the normal range on the M-ACE had higher Aβ1-42 (median 38.52 vs. 27.35 pg/mL, p = 0.02) and apoE concentrations (median 125.0 vs. 65.73 μg/mL, p = 0.002), and a higher Aβ42/40 ratio (median 0.39 vs. 0.29 p < 0.000) compared to the DC group. Considering the study groups, the highest Aβ42/40 ratio was found among the HC group (median 0.47). The median score for the M-ACE scale was 3 points lower when HTN and DM coexisted, compared to the sole diagnosis of HTN (25 points and 28 points, respectively). A higher number of years of education correlated with better M-ACE results. Lipid and uric acid concentrations were not related to M-ACE or MMSE scores. An inverse relationship connected Aβ1-40 and Aβ1-42 to BMI, the duration of HTN treatment, and glycated hemoglobin. Conclusions: Aβ1-42, APOE, and Aβ42/40 are not only correlated with cognition but also related to patient's disease profile. The coexistence of DM and HTN was associated with the most significant decline in cognitive functioning. However, a higher number of years of education may protect against the development of dementia in old age. The roles of cholesterol and uric acid in cognitive decline are still inconclusive.

Introduction: The rates of pediatric ischemic stroke incidence have more than doubled over the past 3-4 decades; however, pediatric posterior circulation strokes are even more uncommon. These rising incidence rates have led to increasing awareness of pediatric strokes and the development of institutional guidelines regarding these patients to optimize outcomes when possible. Case Report: We describe a rare case of acute ischemic posterior circulation stroke in a 14-year-old previously healthy adolescent boy who presented with right-sided facial droop, dysarthria, and right-sided hemiplegia. An MRI of the brain demonstrated an acute infarct in the brainstem, and an echocardiogram demonstrated a patent foramen ovale (PFO). We also discuss how to localize brainstem lesions to a specific location within the brainstem and associated blood supply using symptomatology. Conclusions: All stroke patients require evaluation for possible etiologies of stroke and possible underlying risk factors. Nearly half of patients who suffer from cryptogenic stroke are found to have a PFO, and adult studies have shown that PFO closure is associated with reduced recurrent cryptogenic strokes, although pediatric-specific data is lacking. If a posterior stroke is suspected, specifically in the brainstem, then the Brainstem Rules of Four may be utilized to localize these lesions and identify blood supply using simplified knowledge of the brainstem anatomy.

Background: Antibodies to glutamic acid decarboxylase (anti-GAD) can give rise to stiff person syndrome (SPS), an infrequent autoimmune condition of the central nervous system marked by fluctuating muscular rigidity and stimulus-evoked spasms. Disturbances in eye-movement control are rarely identified yet may provide insight into underlying neural involvement. Methods: Two individuals with anti-GAD-related SPS showing distinctive ocular-motor abnormalities were examined with quantitative videonystagmography, supplemented by representative video documentation. Results: Recordings demonstrated varied patterns of ocular-motor disturbance, including reduced smooth-pursuit accuracy, delayed saccadic initiation, dysmetria, intrusive saccades, and several nystagmus types. Partial improvement occurred after immunomodulatory therapy. Conclusions: These findings extend current understanding of the anti-GAD SPS phenotype and indicate that quantitative analysis of eye movements may offer a sensitive, non-invasive marker of disease activity. Larger, prospective studies are needed to clarify prevalence and responsiveness to treatment.