Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy. Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24–36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models. Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27–0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14–2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25–1.11, p = 0.092). Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.

Background and purpose The aim was to investigate whether cerebral small vessel disease (CSVD) markers and the total CSVD burden are associated with functional outcome, mortality, stroke recurrence and haematoma expansion in patients with spontaneous intracerebral haemorrhage (ICH). Methods Following a previously registered protocol (PROSPERO protocol: CRD42021287743), PubMed, Web of Science and Embase were systematically searched to identify relevant literature up to November 2021. Cohort studies that examined the association between CSVD markers (white matter hyperintensity [WMH], lacune, enlarged perivascular space [EPVS], cerebral microbleed [CMB] and brain atrophy) or CSVD burden and prognosis in patients with ICH were included. The pooled estimates were calculated using random effects models. Results Forty‐one studies with 19,752 ICH patients were pooled in the meta‐analysis. WMH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.32–1.70), lacune (OR = 1.32, 95% CI 1.18–1.49), CMB (OR = 2.60, 95% CI 1.13–5.97) and brain atrophy (OR = 2.22, 95% CI 1.48–3.31) were associated with worse functional outcome. CSVD markers concerning increased risk of mortality were WMH (OR = 1.57, 95% CI 1.38–1.79) and brain atrophy (OR = 1.84, 95% CI 1.11–3.04), and markers concerning increased risk of stroke recurrence were WMH (OR = 1.62, 95% CI 1.28–2.04) and lacune (OR = 3.00, 95% CI 1.68–5.37). Enlarged perivascular space was not related to prognosis. There was a lack of association between CSVD markers and haematoma expansion. CSVD burden increased the risk of worse functional outcome, mortality and stroke recurrence by 57%, 150% and 44%, respectively. Conclusions In patients with spontaneous ICH, WMH, lacune, CMB, brain atrophy and the total CSVD burden are associated with substantially increased risk of worse functional outcome, mortality or stroke recurrence.

Background and purpose:The aim was to investigate the associations of haemorrhagic transformation (HT) and its clinical and radiological subtypes with functional outcome, mortality, early neurological deterioration (END) and neurological complications in patients with acute ischaemic stroke (AIS). Methods: A systematic review and meta-analysis of observational studies on the associations of overall HT, clinical HT subtypes (asymptomatic intracerebral haemorrhage [aICH] and symptomatic intracerebral haemorrhage [sICH]) or radiological HT subtypes (haemorrhagic infarction [HI-1 or HI-2] and parenchymal haemorrhage [PH-1 or PH-2]) with prognosis in patients with AIS was performed. PubMed, Web of Science and Embase were systematically searched. Random effects models were used to calculate pooled estimates.Results: Fifty-one studies with 100,510 patients were pooled in the meta-analysis.Overall HT was associated with worse functional outcome (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.55-2.90), increased mortality (OR 1.87, 95% CI 1.52-2.30), END (OR 2.35, 95% CI 1.46-3.77), early-onset seizures (OR 2.58, 95% CI 1.63-4.10) and poststroke epilepsy (OR 2.23, 95% CI 1.11-4.49). For clinical subtypes, sICH remained significantly associated with the aforementioned poor prognoses except post-stroke epilepsy, and aICH was associated with worse functional outcome but was unrelated to mortality.For radiological subtypes, PH (especially PH-2) was strongly associated with poor prognosis. HI-2 was associated with worse functional outcome, and HI-1 was associated with a lower risk of mortality and END.Conclusions: Regardless of whether AIS patients undergo thrombolysis or thrombectomy, overall HT, sICH and PH (especially PH-2) are associated with a substantially increased risk of worse functional outcome, mortality, END or neurological complications. The presence of aICH is related to worse functional outcome but is independent of increased mortality. HI-2 impairs functional independence, and HI-1 does not cause neurological impairment.

Acute ischemic stroke is a serious disease that endangers human health. In our efforts to develop an effective therapy, we previously showed that the potent, highly selective inhibitor of soluble epoxide hydrolase called 1-trifuoromethoxyphenyl-3-(1propionylpiperidin-4-yl) urea (TPPU) protects the brain against focal ischemia in rats. Here we explored the mechanism of TPPU action by assessing whether it could preserve blood-brain barrier integrity and reduce apoptosis in the brain during permanent middle cerebral artery occlusion in male Sprague-Dawley rats. TPPU administration at the onset of stroke and once daily thereafter led to smaller infarct volume and brain edema as well as milder neurological deficits. TPPU significantly inhibited the activity of soluble epoxide hydrolase and matrix metalloproteases 2 and 9, reducing 14,15-DHET levels, while increasing expression of tight junction proteins. TPPU decreased numbers of apoptotic cells by down-regulating the pro-apoptotic proteins BAX and Caspase-3, while upregulating the anti-apoptotic protein BCL-2. Our results suggest that TPPU can protect the blood-brain barrier and reduce the apoptosis of brain tissue caused by ischemia.

Objective: We retrospectively analyzed clinical characteristics, etiology, and mortality risk factors in pediatric cases of non-traumatic spontaneous intracerebral hemorrhage.Methods: This study involved children between 29 days and 18 years old with confirmed spontaneous intracerebral hemorrhage based on head CT or MRI at the Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital from January 2008 to March 2020. Demographic and clinical characteristics, etiology, imaging, and treatment data were collected at baseline. Potential risk factors of in-hospital death were identified using univariate analysis and multivariate logistic regression.Result: A total of 200 children (126 males, median age 5 years) were included in the study. Clinical symptoms of spontaneous intracerebral hemorrhage were typically non-specific (79.5%). One third of patients (31.1%) had a Glasgow Coma Scale score (GCS) ≤ 8, and nearly two-thirds (60.5%) showed a combination of ventricular hemorrhage or subarachnoid hemorrhage. Supratentorial hemorrhage was more common. Cerebrovascular disease (37.0%) and hematological disease (33.5%) were the most frequent etiologies of spontaneous intracerebral hemorrhage. Most patients (74.5%) received non-surgical treatment, while 25.5% received surgical treatment. After an average of 12 days of treatment, 167 children (83.5%) survived and 33 (16.5%) died. Multivariate logistic regression showed herniation syndrome, and low GCS (≤ 8) to be associated with increased risk of mortality, while hemorrhage due to arteriovenous malformation was associated with lower risk of mortality.Conclusion: Our data suggest that cerebrovascular disease is the most common cause of spontaneous intracerebral hemorrhage among children, and that arteriovenous malformation is associated with lower risk of death in hospital. Conversely, the presence of herniation syndrome, low GCS (≤ 8) increase risk of in-hospital mortality. Our results underscore the importance of timely imaging and supplementary examinations in cases of suspected spontaneous intracerebral hemorrhage.