High risk of ischaemic stroke amongst patients with hereditary haemorrhagic telangiectasia.

BACKGROUND AND PURPOSE: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disease with fragile blood vessels and vascular malformations, potentially causing neurological manifestations, including stroke and cerebral abscesses. The study aimed to investigate neurological manifestations in the Danish HHT database, focusing on pulmonary arteriovenous malformations (PAVMs) as a risk factor for cerebral events. METHODS: Retrospective analysis of the Danish HHT database was conducted, cross-referencing neurological outcomes with the Danish Apoplexy Register for accuracy. Patients were stratified by HHT type. Primary outcomes included ischaemic stroke, transient ischaemic attack and cerebral haemorrhage. Secondary outcomes comprised age, age at HHT diagnosis, age at cerebral ischaemic event, and PAVM and cerebral arteriovenous malformation status. RESULTS: Six hundred and sixty-four HHT patients were included. PAVM was diagnosed in 54% of patients, with higher prevalence in HHT type 1 (70%) compared to HHT type 2 (34%) and juvenile polyposis HHT (66%). Ischaemic stroke or transient ischaemic attack occurred in 12.5%, with a higher risk associated with macroscopic PAVM. Logistic regression showed a nearly 10 times increased risk of ischaemic stroke with macroscopic PAVM. Cerebral abscesses occurred in 3.2% of patients, all with macroscopic PAVM. Incomplete PAVM closure increased cerebral abscess risk. CONCLUSION: This study provides valuable insights into the prevalence of neurological manifestations and vascular events in HHT patients. The presence of PAVM was associated with an increased risk of ischaemic stroke, highlighting the importance of early screening and intervention. The findings emphasize the need for comprehensive management strategies targeting both vascular and neurological complications in HHT patients, especially regarding secondary stroke prevention.

Insight into the pathophysiological advances and molecular mechanisms underlying cerebral stroke: current status.

Molecular pathways involved in cerebral stroke are diverse. The major pathophysiological events that are observed in stroke comprises of excitotoxicity, oxidative stress, mitochondrial damage, endoplasmic reticulum stress, cellular acidosis, blood-brain barrier disruption, neuronal swelling and neuronal network mutilation. Various biomolecules are involved in these pathways and several major proteins are upregulated and/or suppressed following stroke. Different types of receptors, ion channels and transporters are activated. Fluctuations in levels of various ions and neurotransmitters have been observed. Cells involved in immune responses and various mediators involved in neuro-inflammation get upregulated progressing the pathogenesis of the disease. Despite of enormity of the problem, there is not a single therapy that can limit infarction and neurological disability due to stroke. This is because of poor understanding of the complex interplay between these pathophysiological processes. This review focuses upon the past to present research on pathophysiological events that are involved in stroke and various factors that are leading to neuronal death following cerebral stroke. This will pave a way to researchers for developing new potent therapeutics that can aid in the treatment of cerebral stroke.

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone.

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L., known as "Abhal" in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-ß) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR-induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-ß and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke.

Association of CYP4A22 gene polymorphisms with cerebral stroke risk in the Chinese Han population.

BACKGROUND: Cerebral stroke (stroke) is an acute cerebrovascular disease with high incidence and mortality. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of CYP4A22 and stroke risk in the Chinese Han population. METHODS: A total of 550 stroke patients and 545 healthy people were recruited. Four candidate SNPs (rs76011927 T/C, rs12564525 C/T, rs2056900 A/G and rs4926581 T/G) of CYP4A22 were screened. The association between CYP4A22 SNPs and stroke risk was assessed using genetic models and the relationship between SNPs and clinical biochemical indicators was analyzed by one-way analysis of variance (one-way ANOVA). RESULTS: The overall analysis showed that rs12564525 could significantly reduce stroke risk only under the recessive model (OR = 0.72, 95% CI 0.53-0.99), but rs2056900 and rs4926581 were significantly associated with increased stroke risk under the homozygote (OR = 1.49, 95% CI 1.06-2.09; OR = 1.49, 95% CI 1.06-2.10), heterozygote (OR = 1.49, 95% CI 1.11-2.00; OR = 1.48, 95% CI 1.11-1.99), additive (OR = 1.22, 95% CI 1.03-1.45; OR = 1.22, 95% CI 1.03-1.45) and dominant (OR = 1.49, 95% CI 1.13-1.97; OR = 1.49, 95% CI 1.13-1.96) models (all p < 0.05). Subgroup analyses further indicated that rs2056900 and rs4926581 could significantly increase stroke risk in participants aged >63 years and females. In addition, high-density lipoprotein cholesterol (HDL-C) levels differed considerably among different genotypes of rs12564525, rs2056900 and rs4926581. CONCLUSIONS: This study revealed that CYP4A22 SNPs are associated with stroke risk in the Chinese Han population, and in particular, rs2056900 and rs4126581 have a significant correlation with increased stroke risk.

The Diagnostic Model of Ligusticum Chuanxiong Hort. Against Cerebral Stroke Using Network Pharmacology and Transcriptomics Analyses.

BACKGROUND: Cerebral stroke is a leading cause of death and disability worldwide. Ligusticum Chuanxiong Hort. (LCH), a well-known Chinese herb, is widely used for the treatment of cerebral stroke. This study aimed to investigate the underlying mechanisms of LCH in cerebral stroke and develop a diagnostic model. METHODS: We employed network pharmacology analyses to identify the active compounds, targets, and underlying mechanisms of LCH for treating cerebral stroke. Molecular docking was performed to visualize the binding site between the core active compounds and hub targets. Furthermore, a diagnostic model for cerebral stroke was constructed based on transcriptomic analysis. RESULTS: Our findings revealed that LCH contains multiple active ingredients, including oleic acid and caffeic acid. Protein-protein interaction network analysis identified IL1B, CCL2, MAPK3, PTGS2, JUN, MMP9, TLR4, HIF1A, PPARA, FOS, PTEN, NFE2L2, TLR2, TIMP1, and SOD2 as the top 15 hub genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted the enrichment of TNF and IL-17 signaling pathways. Molecular docking analysis demonstrated binding sites between oleic acid, caffeic acid, and MMP9, PPARP, PTEN, and TIMP1. The diagnostic model indicated that FOS, MMP9, PPARA, PTEN, TIMP1, and TLR2 serve as blood biomarkers for cerebral stroke. CONCLUSIONS: This study demonstrates that LCH alleviates the symptoms following cerebral stroke through interactions with the TNF and IL-17 signaling pathways. The findings contribute to a better understanding of the therapeutic mechanisms of LCH and offer insights into the development of a diagnostic model for cerebral stroke.

Follow-up outcomes of different bypass surgical modalities for adults with ischaemic-type moyamoya disease.

PURPOSE: The preferred surgical method for treating adults with moyamoya disease (MMD) remains controversial. The purpose of this study was to compare the efficacy of different surgical methods in the treatment of adults with ischaemic-type MMD. METHODS: We retrospectively analyzed the data of patients with ischaemic-type MMD who underwent indirect bypass (IB), direct bypass (DB), or combined bypass (CB) at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2019. Postoperative complications, improvements in neurological function, haemodynamics, recurrent stroke and neovascularization were compared. RESULTS: A total of 310 adults (371 hemispheres) with ischaemic-type MMD were included in our study. Ninety, 127, and 154 hemispheres underwent IB, DB and CB, respectively. A total of 24 (6.5%) ischaemic events and 8 (2.8%) symptomatic hyperperfusion events occurred after the operations. There was no significant difference in postoperative complications among the three types of surgery (p = 0.300). During the follow-up period, there were 21 cases (5.7%) of recurrent ischaemia and 12 cases (3.2%) of recurrent haemorrhage. Kaplan-Meier survival analysis showed that the ischaemia-free survival of the CB group was significantly longer than that of the IB group (p = 0.047), but there was no significant difference in haemorrhage-free survival among the three groups (p = 0.660). Six months after the operation, DB and CB were superior to IB in improving cerebral blood flow and neovascularization (p = 0.002), but there was no significant difference in the improvement of neurological function among the three groups at the last follow-up (p = 0.784). CONCLUSION: The three surgical methods achieved satisfactory results in the treatment of ischaemic-type MMD. DB and CB can significantly improve haemodynamics and reduce recurrent stroke. In terms of improving neurological function, the curative effect of the three surgical methods remains to be further explored.

Internal border zone injury predicts the functional outcome of acute MCA stroke patients.

BACKGROUND AND PURPOSE: Classification of deep (D), superficial (S) MCA territories and their junctional vascular area (the internal border zone, IBZ) can help to identify patients most likely to benefit from aggressive reperfusion therapy after stroke. We tested the prognostic value of an IBZ injury compared to DWI-ASPECTS and infarct volume. MATERIALS AND METHODS: DW lesions of 168 patients with acute (4.2±6.5 h) MCA strokes were retrospectively examined and manually delineated. Patients with haemorrhagic transformation or other neurological diseases were excluded. Clinical data were recorded within 24 h following symptom onset and 48 h for patients who benefited from reperfusion therapy. The occurrence of an IBZ injury was determined using a standardized stereotaxic atlas. Performance to predict a good outcome (mRS<3 at 3 months) was estimated through ROC curves for DWI-ASPECTS≤6, lesion volume≥100 mL and IBZ injury. Logistic regression models were performed to estimate independent outcomes for infarct volume and IBZ injury. RESULTS: Infarcts involving the IBZ were larger (94.9±98.8 mL vs. 30.2±31.3 mL), had higher NIHSS (13.8±7.2 vs. 7.2±5.7), more frequent MCA occlusions (64.9% vs. 28.3%), and worse outcomes (mRS 3.0±1.8 vs. 1.9±1.7), and were less responsive to IVtPA (34±47% vs. 55±48% of NIHSS improvement). The area under the ROC curves was comparable between the occurrence of IBZ injury (0.651), ASPECTS≤6 (0.657) and volume≥100 mL (0.629). Logistic regression analyses showed an independent effect of an IBZ injury, especially for superficial MCA strokes and for patients who benefited from reperfusion therapy. CONCLUSION: An IBZ injury is an early and independent marker of stroke severity, functional prognosis and treatment responsiveness.

Comparison of Two Automated Computed Tomography Perfusion Applications to Predict the Final Infarct Volume After Thrombolysis in Cerebral Infarction 3 Recanalization.

BACKGROUND: Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact. METHODS: Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences. RESULTS: Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings. CONCLUSIONS: By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.

Lower uric acid level may be associated with hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND: Previous studies have shown that uric acid (UA) is a powerful water-soluble antioxidant and free radical scavenger for humans. However, the relationship between serum uric acid (SUA) and hemorrhagic transformation (HT) is still controversial. To address this challenge, we aimed to explore the association between serum UA and HT in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: A retrospective analysis was conducted in patients with anterior circulation AIS who underwent IVT at Affiliated Hospital of Qingdao University from 2016 to 2021. HT was evaluated by CT or MRI within 7 days after admission. Baseline demographic, clinical, and laboratory data were compared between the HT and non-HT groups, and between different types of HT groups which were documented according to the European Cooperative Acute Stroke Study III Classification (ECASS III). RESULTS: A total of 727 AIS patients were enrolled, including 112 patients who experienced HT (HT group) and 615 patients who did not experience HT (non-HT group). Patients with HT had significantly lower UA levels compared to those without HT (253.65 ± 97.75 vs 315.97 ± 96.42, p < 0.001); however, there was no significant difference for UA levels in different types of HT (p = 0.907). After adjusting confounders, patients in the fourth UA quartile showed a significant decrease in HT compared with those in the first quartile (OR 0.266, 95% CI 0.107-0.661, p = 0.006). The best cutoff value was identified as 218.5 µmol/L after analysis. CONCLUSIONS: These findings suggest that low levels of UA may be associated with HT after IVT.

Sinensetin attenuates oxygen-glucose deprivation/reperfusion-induced neurotoxicity by MAPK pathway in human cerebral microvascular endothelial cells.

Sinensetin is a polymethoxylated flavone with anti-inflammatory and anti-oxidative activities. This work aimed to explore the function and mechanism of sinensetin in oxygen and glucose deprivation/reperfusion (OGD/R)-induced neurotoxicity. The overlapping target genes of cerebral stroke and sinensetin were determined according to GeneCards and ParmMapper tools and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Human cerebral microvascular endothelial cells (HCMECs) were stimulated with OGD/R. Neurotoxicity was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, qRT-PCR, and TUNEL analysis. The proteins (p38, JNK, and ERK) in mitogen-activated protein kinase (MAPK) signaling were measured using Western blotting. Total of 50 overlapping target genes of cerebral stroke and sinensetin were predicted. Pathway analysis showed they might be involved in the MAPK pathway. Sinensetin attenuated OGD/R-induced neurotoxicity by mitigating viability reduction, LDH release, ROS generation, inflammatory response, and apoptosis in HCMECs. Sinensetin weakened OGD/R-induced activation of the MAPK pathway via decreasing the phosphorylation of p38, JNK, and ERK. The pathway inhibitors mitigated the activation of the MAPK signaling, and sinensetin exacerbated this effect. The inhibitors reversed OGD/R-induced neurotoxicity in HCMECs, and sinensetin contributed to this role. Overall, sinensetin prevents OGD/R-induced neurotoxicity through decreasing the activation of MAPK pathway.

Fraxetin protects rat brains from the cerebral stroke via promoting angiogenesis and activating PI3K/Akt pathway.

OBJECTIVE: Fraxetin has antioxidant, anti-inflammation and neuroprotective functions, however, its role in ischemic stroke is still vague. Herein, this study delves into the underlying mechanism. METHODS: Ischemia and reperfusion operation were performed to establish the cerebral stroke rat models. The brain functions were evaluated with neurological score. The brain infarcted volume in fraxetin group was measured by 2,3,5-triphenyltetrazolium chloride staining. The blood-brain barrier permeability, CD34 enrichment, and the brain water content were measured by Evans blue staining, immunofluorescence staining, and wet-dry method, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were applied to examine the levels of angiogenesis- and PI3K/Akt pathway-related factors. MTT and tube formation assays were used to measure the viability and tube formation of HUVECs. RESULTS: Fraxetin decreased the brain injury-related neurological score, brain infarction, and cerebral edema and maintained blood-brain barrier permeability, whereas it promoted the angiogenesis in ischemia-damaged brain via enhancing CD34 enrichment, the expressions of VEGF, Ang-1, Tie-2, and CD-31, viability of HUVECs, as well as activating the phosphorylation of PI3K and Akt. Importantly, wortmannin (a specific PI3K inhibitor) impeded the fraxetin-induced cell viability, angiogenesis, and phosphorylation of Akt and PI3K in HUVECs. CONCLUSIONS: Fraxetin has protective effects on the brain ischemia-reperfusion injury and promotes angiogenesis for cerebral repair via phosphorylation of PI3K and Akt.

Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor.

The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30 mg/kg) for 28 days. The spatial memory was studied by Morris water maze (MWM). After 4 weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30 mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15 mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.

Uncrossed corticospinal tract in health and genetic disorders: Review, case report, and clinical implications.

BACKGROUND AND PURPOSE: Crossing pathologies of the corticospinal tract (CST) are rare and often associated with genetic disorders. However, they can be present in healthy humans and lead to ipsilateral motor deficits when a lesion to motor areas occurs. Here, we review historical and current literature of CST crossing pathologies and present a rare case of asymmetric crossing of the CST. METHODS: Description of the case and systematic review of the literature were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed database was searched for peer-reviewed articles in English since 1950. All articles on ipsilateral stroke, uncrossed CST, and associated neurologic disorders were screened. Furthermore, a literature review between the years 1850 and 1980 including articles in other languages, books, opinions, and case studies was conducted. RESULTS: Only a few descriptions of CST crossing pathologies exist in healthy humans, whereas they seem to be more common in genetic disorders such as horizontal gaze palsy with progressive scoliosis or congenital mirror movements. Our patient presented with aphasia and left-sided hemiparesis. Computed tomographic (CT) scan revealed a perfusion deficit in the left middle cerebral artery territory, which was confirmed by diffusion-weighted magnetic resonance imaging (MRI), so that thrombolysis was administered. Diffusion tensor imaging with fibre tracking revealed an asymmetric CST crossing. CONCLUSIONS: The knowledge of CST crossing pathologies is essential if a motor deficit occurs ipsilateral to the lesion side. An ipsilateral deficit should not lead to exclusion or delay of therapeutic options in patients with suspected stroke. Here, a combined evaluation of CT perfusion imaging and MRI diffusion imaging may be of advantage.

MFGE8 mitigates brain injury in a rat model of SAH by maintaining vascular endothelial integrity via TIGß5/PI3K/CXCL12 signaling.

Leaked blood components, injured endothelial cells, local inflammatory response and vasospasm may converge to promote microthrombosis following subarachnoid hemorrhage (SAH). Previously, we showed that the milk fat globule-epidermal growth factor 8 (MFGE8) can mitigate SAH-induced microthrombosis. This present study was aimed to explore the molecular pathway participated in MFGE8-dependent protection on vascular endothelium. Immunofluorescence, immunoblot and behavioral tests were used to determine the molecular partner and signaling pathway mediating the effect of MFGE8 in vascular endothelium in rats with experimental SAH and controls, together with the applications of RNA silencing and pharmacological intervention methods. Relative to control, recombinant human MFGE8 (rhMFGE8) treatment increased 5-bromo-2'-deoxyuridine (BrdU) labeled new endothelial cells, reduced TUNUL-positive endothelial cells and elevated the expression of phosphatidylinositol 3-kinase (PI3K) and chemokine (C-X-C motif) ligand 12 (CXCL12), in the brains of SAH rats. These effects were reversed by MFGE8 RNA silencing, as well as following cilengitide and wortmannin intervention. These results suggest that MFGE8 promotes endothelial regeneration and mitigates endothelial DNA damage through the activation of the TIGß5/PI3K/CXCL12 signaling pathway.

Efficacy of Vestibular Rehabilitation in Patients With Neurologic Disorders: A Systematic Review.

OBJECTIVE: The aim of this systematic review is to critically assess the effectiveness of vestibular rehabilitation (VR) administered either alone or in combination with other neurorehabilitation strategies in patients with neurologic disorders. DATA SOURCES: An electronic search was conducted by 2 independent reviewers in the following databases: MEDLINE (PubMed), the Physiotherapy Evidence Database, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: All clinical studies carried out on adult patients with a diagnosis of neurologic disorders who performed VR provided alone or in combination with other therapies were included. DATA EXTRACTION: Screening of titles, abstracts, and full texts and data extraction were undertaken independently by pairs of reviewers. Included studies were quality appraised using a modified version of the Newcastle-Ottawa Scale. DATA SYNTHESIS: The summary of results was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Twelve studies were included in the review. All the included studies, with 1 exception, report that improvements provided by customized VR in subject affected by a central nervous system diseases are greater than traditional rehabilitation programs alone. CONCLUSIONS: Because of the lack of high-quality studies and heterogeneity of treatments protocols, clinical practice recommendations on the efficacy of VR cannot be made. Results show that VR programs are safe and could easily be implemented with standard neurorehabilitation protocols in patients affected by neurologic disorders. Hence, more high-quality randomized controlled trials of VR in patients with neurologic disorders are needed.

Three-pillar expansive craniotomy: a new surgical technique for cerebral decompression in children.

PURPOSE: The aim of this study is to conduct a retrospective review of data obtained in all consecutive patients who had undergone cerebral decompression using the 3-pillar expansive craniotomy (3PEC) in our hospital between 2016 and 2020. METHODS AND RESULTS: We developed a novel craniotomy technique using expansion cranioplasty in patients with traumatic brain injury or stroke, which could relieve intracranial hypertension, maintain cerebral protection, and avoid subsequent cranial repair. Sixteen patients aged 2-18 years old underwent the 3PEC. Two patients, who presented very severe neurological conditions at the admission, died. All surviving patients showed good neurological outcome. None of the survived patients presented with bone flap resorption or sinking flap syndrome. CONCLUSION: The role of decompressive craniectomy has been recently questioned in the pediatric population by the use of decompressive craniotomy. In this limited study of children patients experiencing stroke or traumatic brain injury, 3PEC was proved useful in reducing intracranial pressure (ICP), thus, questioning the role of decompressive craniectomy in children. The technique effectively reduces postoperative complications and eliminates subsequent cranioplasty procedures otherwise introduced by traditional decompressive craniectomy.

The Role of Thromboxane in the Course and Treatment of Ischemic Stroke: Review.

Cardiovascular diseases are currently among the leading causes of morbidity and mortality in many developed countries. They are distinguished by chronic and latent development, a course with stages of worsening of symptoms and a period of improvement, and a constant potential threat to life. One of the most important disorders in cardiovascular disease is ischemic stroke. The causes of ischemic stroke can be divided into non-modifiable and modifiable causes. One treatment modality from a neurological point of view is acetylsalicylic acid (ASA), which blocks cyclooxygenase and, thus, thromboxane synthesis. The legitimacy of its administration does not raise any doubts in the case of the acute phase of stroke in patients in whom thrombolytic treatment cannot be initiated. The measurement of thromboxane B2 (TxB2) in serum (a stable metabolic product of TxA2) is the only test that measures the effect of aspirin on the activity of COX-1 in platelets. Measurement of thromboxane B2 may be a potential biomarker of vascular disease risk in patients treated with aspirin. The aim of this study is to present the role of thromboxane B2 in ischemic stroke and to present effective therapies for the treatment of ischemic stroke. Scientific articles from the PubMed database were used for the work, which were selected on the basis of a search for "thromboxane and stroke". Subsequently, a restriction was introduced for works older than 10 years, those concerning animals, and those without full text access. Ultimately, 58 articles were selected. It was shown that a high concentration of TXB2 may be a risk factor for ischemic stroke or ischemic heart disease. However, there is insufficient evidence to suggest that thromboxane could be used in clinical practice as a marker of ischemic stroke. The inclusion of ASA in the prevention of stroke has a beneficial effect that is associated with the effect on thromboxane. However, its insufficient power in 25% or even 50% of the population should be taken into account. An alternative and/or additional therapy could be a selective antagonist of the thromboxane receptor. Thromboxane A2 production is inhibited by estrogen; therefore, the risk of CVD after the menopause and among men is higher. More research is needed in this area.

[Internal carotid artery dissection in the neurologist's practice - a case study]. / Rozwarstwienie tetnicy szyjnej wewnetrznej w praktyce neurologa ­ opis przypadku.

Dissection of the interior carotid artery is rare in the general population. It can however be a potentially life-threatening condition. In the group of patients below 45 years of age, it constitutes a fairly common cause of cerebral stroke. A CASE REPORT: The study describes the case of a patient with the right interior carotid artery dissection, sustained most probably in the course of work. The patient was admitted to hospital for a severe headache of a few days' duration accompanied by Horner's syndrome on the right side. Promptly undertaken diagnostic procedures allowed for immediate diagnosis and application of the right treatment. The check-up examinations performed showed a healed artery and withdrawal of the neurological syndrome. CONCLUSIONS: The case emphasizes the role of prompt diagnosis and treatment in preventing the development of more serious complications. The article refers also to the standards of treating the dissection of the interior carotid artery which still arouse controversies.

[Treatment of acute tandem occlusion of arteries of anterior cerebral circulation without emergency stenting]. / Lechenie ostroi tandemnoi okkliuzii arterii perednei tsirkuliatsii golovnogo mozga bez ékstrennogo stentirovaniia.

The article deals with problems of endovascular treatment of acute tandem and isolated occlusions of arteries of the anterior cerebral circulation, as well as the problem of reocclusions and new occlusions of these target arteries in the early postoperative period after thrombectomy. PURPOSE: To determine the effect of reocclusions and new, previously not identified occlusions of the carotid artery and middle cerebral artery after cerebral thrombectomy on the outcomes of ischaemic stroke, as well as to substantiate feasibility of endovascular policy without simultaneous carotid stenting in thrombectomy in case of tandem occlusions of arteries of the anterior cerebral circulation. PATIENTS AND METHODS: We studied the results of endovascular treatment of 52 patients with acute ischaemic stroke, including 26 patients with combined occlusions of the internal carotid and middle cerebral arteries (group 1) and 26 patients with isolated occlusion of the M1 segment of the middle cerebral artery or its equivalent (group 2). The groups were compared using the Chi-squared and Mann-Whitney test, and the effect of the factors was assessed by calculating the relative risk. RESULTS: Disability of patients in group 1 was significantly two-fold higher as compared with group 2. Differences in mortality and frequency of a good functional outcome (0-2 points on the Rankin scale) were, on the contrary, insignificant. Reocclusion of the internal carotid artery demonstrated no significant influence on outcomes of the disease in combined type of the lesion. Reocclusion of the target vessel after thrombectomy significantly decreased the probability of a good functional outcome in patients 1.7-fold (p<0.05), as well as increased the relative risk of disability 4-fold in initially isolated occlusion of the middle cerebral artery (p<0.05). CONCLUSION: Surgical policy aimed at thrombectomy from the middle cerebral artery in the presence of tandem occlusions of the internal carotid artery and middle cerebral artery without emergency carotid stenting is safe and efficient in acute period of ischaemic stroke. Reocclusion of the middle cerebral artery after performed thrombectomy related to its isolated occlusion increased the probability of patients' disability. Newly identified in the postoperative period occlusion of the internal carotid artery in thrombectomy from the middle cerebral artery also increased the risk of disability.

TRIM62 knockout protects against cerebral ischemic injury in mice by suppressing NLRP3-regulated neuroinflammation.

Cerebral stroke is a leading global cause for mortality and disability. However, its pathogenesis is still unclear. Most tripartite motif (TRIM) family proteins, including TRIM62, have E3 ubiquitin ligase activities, and have multiple functions in regulating cellular processes. Nevertheless, the effects of TRIM62 on cerebral stroke still remain vague. Here, we reported that TRIM62 expression was markedly up-regulated in oxygen and glucose deprivation (OGD)-treated microglial cells. After cerebral ischemia, significantly elevated expression of TRIM62 was detected in peri-infarct area of wild type (WT) mice. The TRIM62 knockout (KO) mice exhibited alleviated apoptosis and neuroinflammation in the ischemic brain, eventually attenuating the stroke outcomes. Both in vitro and in vivo studies showed that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome was dramatically activated in cerebral ischemia/reperfusion (I/R) conditions, while being ameliorated in TRIM62-KO mice, contributing to the suppression of neuroinflammatory response. Importantly, the in vitro experiments showed that OGD could induce the K63-ubiquitination of TRIM62 and the interaction between TRIM62 and NLRP3. In addition, adenovirus-regulated TRIM62 over-expression promoted the NLRP3 and nuclear factor κB (NF-κB) signaling, along with elevated interleukin-1ß (IL-1ß) and IL-18 transcriptional activities. Together, our results demonstrated that TRIM62 suppression was strongly protective in ischemic stroke through inhibiting NLRP3-regulated neuroinflammation.