Abstract: Beyond its direct neuronal effects, alpha-synuclein (α-synuclein) interacts with microglia, influencing disease progression through mechanisms that are not fully understood. Microglia may contribute to the propagation of α-synuclein pathology through pathophysiological pathways such as incomplete degradation and intercellular transfer of aggregates. Research into α-synuclein-microglia interactions has revealed their dual role in aggregate clearance and inflammation, highlighting microglia as both protective and deleterious agents in synucleinopathies. Human genetics suggest that neuronal-glial crosstalk plays a causal role in α-synucleinopathies. Leucine-rich repeat kinase 2 (LRRK2) may originate in the microglia based on studies with induced pluripotent stem cells (iPSCs). Other IPSC-derived microglia were glycoprotein nonmetastatic melanoma protein B and lysolipid transporter 1 (SPNS1) in Parkinson’s disease (PD). Another source of α-synuclein could be neuronal, and the discovery of cyclic guanosine monophosphate–adenosine monophosphate (AMP) synthase/stimulator of interferon genes leading to stimulation of interferons and LRRK2, especially in dopamine neurons, is a supporting finding. Multiple system atrophy (MSA) is an oligodendroglial disease, and some of the targets for management may involve mitochondrial dysfunction, iron deposition, lipid droplets, cytoskeleton disruption, proteasome dysfunction, and tubulin polymerization, promoting protein-like proteins containing p25α. The aim of this review is to provide a comprehensive overview of the molecular and cellular mechanisms linking α-synuclein and microglial activation in PD and MSA, with a focus on genetic insights, autophagy-related pathways, and emerging therapeutic targets.

Abstract: INTRODUCTION: There is an ongoing controversy on the predictive value of the disperse variables involved in cerebral aneurysm rupture. A better understanding of how such variables interact with each other is needed. OBJECTIVES: The initial aim of the study was to propose how exactly, into a hemodynamic model, such morphologic variables might work together to optimize such predictive rupture value. METHODS: We hypothesized, based on previous research, that the aneurysm rupture phenomenon might be related to hemodynamic interference. Hence, we selected the Helmholtz’s resonator equation because its resemblance to aneurysm morphology and that it may also be used on elastic walls. We collected the morphologic data (transverse area of the neck diameter, the length of the neck, the aneurysm height, length, and width radius) from the unique large enough published series ( n = 425) for ruptured ( n = 140) and no ruptured ( n = 285) aneurysms that included all the required variables by the equation on the same sample. Given that the Helmholtz’s equation also requires as an input variable the speed of the pulse wave (PW), we collected these data from the published series that provides this information by age. This proposed arrangement provided the cerebral aneurysm resonance frequency (the hemodynamic vibratory frequency range, in Hertz, where aneurysms might adsorb most of the oscillating PW energy) for ruptured and no ruptured aneurysms (RAs) by age. Hence, at this point, the working hypothesis was to figure out the predictive value for rupture when the aneurysm resonant frequency (maximal vibratory energy absorption) in Hertz equals the PW frequency range of maximal vibratory energy transmission of 225–275 Hz. RESULTS: What we found is that the mean of the resonance frequency values of the RA series almost entirely matches into the PW frequency range of 225–275 Hz (α < 0.016, β = 0.4, and power = 0.6). Interestingly, the mean of the resonance frequency values for the no RA series barely intersects such PW frequency range (α < 0.024, β = 0.4, and power 0.6). In synthesis, we propose a novel multivariate hemodynamic vibratory interference phenomenon for aneurysm rupture that is activated when the PW frequency matches the resonant frequency of a cerebral aneurysm. The results turned out to have a 99.04% of negative predictive value. DISCUSSION: We hope that a better understanding of this phenomenon might preclude superior treatment strategies. This manuscript aims to provide additional predictive value to better detect patients on a crash course with aneurysm rupture. The required input parameters may be swiftly acquired during an individualized assessment. With this model, PW frequency and hemodynamic interference seem to emerge as novel arterial-damaging factors. CONCLUSION: The Specifity of 97.54%, reflects the ability of the model to correctly identify individuals with lower risk of cerebral aneurysm rupture.

Abstract: INTRODUCTION: Moyamoya disease (MMD) is a cerebrovascular disorder wherein progressive occlusion of the intracranial arteries leads to cerebral ischemia. This study aimed to compare the influence of anesthesia techniques, namely, inhalational anesthesia (INHA) and total intravenous anesthesia (TIVA), on intraoperative cerebral oxygenation and outcomes following combined direct and indirect revascularization for MMD. MATERIALS AND METHODS: This retrospective observational study was conducted at a tertiary care center, where we analyzed data from 73 patients who underwent combined revascularization for MMD between December 2007 and November 2023. Patients with incomplete records or deviations from standard anesthesia protocols were excluded. Collected data included demographics, clinical presentation, anesthetic and surgical details, intraoperative parameters (hemodynamics, jugular oximetry, cerebral oxygenation, and blood gases), and postoperative outcomes (neurological deficits, complications, and modified Rankin scale [mRS] scores). Statistical analyses compared TIVA ( n = 25) and INHA ( n = 22) groups using appropriate tests for continuous and categorical variables. RESULTS: The patient demographic and clinical parameters, such as age, gender, preoperative neurological status, and surgical parameters, were similar between groups. The TIVA group demonstrated low arteriovenous oxygen difference with high jugular venous oxygen saturation along with significantly lower cerebral metabolic rate of oxygen, cerebral oxygen extraction, and lactate-oxygen index compared to the INHA group ( P < 0.05). No differences were observed with regard to postoperative neurological events or mRS scores at discharge and 3 months ( P > 0.005). CONCLUSION: TIVA may enhance cerebral oxygenation and metabolic parameters during MMD revascularization, likely due to propofol’s neuroprotective effects. However, these benefits did not translate into significant improvements in postoperative neurological outcomes or hospital stay.

[This corrects the article on p. 204 in vol. 3, PMID: 30276326.].

Abstract BACKGROUND: Patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are at high risk of early neurological deterioration (END) due to increased platelet activation. OBJECTIVES: The objective of the study was to investigate the safety and efficacy of early antiplatelet therapy in reducing END postthrombolysis, and identify patients who may benefit. METHODS: In this observational study, AIS patients receiving IVT were stratified into the early tirofiban group and the control group according to antiplatelet therapy during the first 24 h following IVT. The primary endpoint was END 4 (the National Institutes of Health Stroke Scale score increase ≥ 4 points) within 72 h following IVT. Binary logistic regression with propensity-score-matching was applied to analyze outcomes between the groups. RESULTS: Of the 319 patients enrolled, 66 in the early tirofiban group and 120 matched controls were analyzed. END 4 occurred in four patients (6.1%) with early tirofiban and 15 patients (12.5%) in the control group. Early tirofiban administration was associated with lower odds of END 4 (adjusted odd ratio, 0.2; 95% confidence interval, 0.1–0.8). Intracranial hemorrhage occurred in 2 (3.0%, none symptomatic) and 3 (2.5%, 2 symptomatic) patients, respectively, with no significant association between early tirofiban and major bleeding or mortality. Early tirofiban was significantly correlated with reduced END 4 among patients aged 66–80 years, those without prestroke antiplatelet therapy, and those with neutral response to IVT (adjusted P < 0.05). CONCLUSION: Early tirofiban therapy following IVT was associated with reduced END without increased bleeding risk. Specific patient subgroups may potentially benefit from early antiplatelet therapy, further confirmation is needed.

Cardiac dysfunction significantly contributes to worsened neurological outcomes following acute ischemic stroke (AIS), posing challenges for prognostication. Holter monitoring is widely used to detect occult cardiac dysfunction and plays a crucial role in managing AIS. This study aimed to evaluate the predictive value of a composite Holter parameter score for prognosis in patients with AIS. A total of 113 patients with AIS within 7 days of stroke onset were enrolled. Holter parameters, including prolonged QT interval, atrial fibrillation, arrhythmia, ST-T elevation, and heart rate variability, were recorded. The primary endpoint was poor prognosis, defined as a 3-month modified Rankin Scale score > 1. Risk factors affecting prognosis were identified using logistic regression analysis. A Holter score incorporating prolonged QT interval, partial ST-T elevation, standard deviation average of the RR interval at 24 h and low frequency during the daytime was developed to predict 3 months prognosis in patients with AIS. Logistic regression analysis demonstrated that the Holter score remained significantly associated with prognosis. The inclusion of the Holter score in the conventional model improved discrimination and net reclassification (net reclassification improvement % = 65.13% [25.01%, 105.24%], integrated discrimination improvement % = 6.99% [1.16%, 12.81%]). The area under the receiver operating characteristic curve was 0.905 (0.831-0.978; P < 0.0001), indicating excellent model fit. The composite Holter score exhibited a promising predictive value for identifying poor prognosis in patients with AIS. Its incorporation into clinical practice may enhance risk stratification and guide treatment decisions in this patient population.TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT03868007).

Significant advancements over the past decade have transformed reperfusion therapy for acute ischemic stroke. Standard treatments, including intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), offer distinct benefits, with recent innovations expanding their efficacy and applicability. IVT, previously limited by a narrow therapeutic window, has seen enhancement with alternative agents such as tenecteplase, which may deliver comparable or superior outcomes to alteplase in selected cases. Expanding indications for EVT, particularly for large vessel occlusions and in extended time windows, have demonstrated promising results, underscoring its effectiveness beyond conventional time constraints. Recent trials further support the use of EVT for patients with large infarct cores in the anterior circulations, although mortality outcomes remain sensitive to treatment timing. In addition, mobile stroke units (MSUs) and prehospital management strategies have emerged as critical components for minimizing delays and improving clinical outcomes. Future research should focus on optimizing reperfusion therapies to individual patient profiles, investigating neuroprotective adjuncts, and expanding the global availability of MSUs to facilitate timely, accessible stroke care.

BACKGROUND:Stroke patients can have various somatosensory abnormalities and a practice–research gap exists among various measurements and treatments. Integrating case reports that bridge this gap may provide a solution to addressing this issue.PURPOSE:This systematic review integrates case reports detailing the physiotherapy management of stroke patients with recognized somatosensory impairments and determines the characteristics related to somatosensory measures, clinical symptoms, and treatments.METHODS:This systematic review was conducted under the Preferred Reporting Items for Systematic Review and Meta-Analysis statement, using PubMed, Cochrane Library, PEDro, CINAHL, and MEDLINE databases for articles published up to February 2024. Two independent authors performed a methodological quality assessment of the case reports.RESULTS:This review included 11 articles of low methodological quality, comprising 13 cases. Physiotherapists used 11 types of somatosensory measures and conducted 11 types of somatosensory training. However, all articles lacked clinical decision-making, causing inadequate accuracy, transparency, and usefulness in the case reports and physiotherapy management.CONCLUSION:Physiotherapy for stroke patients with somatosensory impairments is characterized by a lack of standard somatosensory measures and an unclear effect of somatosensory impairments on motor function, making recovery prediction difficult and causing an unclear process in treatment practices. Addressing this issue requires case reports and clinical research, highlighting the process from somatosensory examination to diagnosis.