Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH. METHODS: Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6 months. RESULTS: One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61 U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4-5) and mild clinical condition (72 vs. 63 U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3-4) compared to those with mild radiologic status (77 vs. 61.5 U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95% CI 1.002-1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95% CI 1.001-1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95% CI 1.041-1.127, p < 0.001). Trend analysis of ALP level based on 103 patients' data revealed a significant decrease in ALP level on post-admission day 7-9 (median; on-admission day vs. post-admission day 7-9, 72 vs. 60 U/L, p = 0.0012; post-admission day 3-5 vs. day 7-9, 70 vs. 60 U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12-14 (median, 84 U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3-5, and 12-14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67 U/L, p = 0.0122; post-admission day 3-5, 80 vs. 64 U/L, p = 0.0044; post-admission day 7-9, 75 vs. 53.5 U/L, p < 0.0001) but not on post-admission day 12-14. CONCLUSIONS: Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.

Comparing the Risk of Shunt-Dependent Hydrocephalus in Patients with Ruptured Intracranial Aneurysms Treated by Endovascular Coiling or Surgical Clipping: An Updated Meta-Analysis.

BACKGROUND: This meta-analysis aimed to evaluate the risk of shunt-dependent hydrocephalus among patients with ruptured intracranial aneurysms treated with either coil placement or clipping. METHODS: A systematic literature search of Embase, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using the STATA 12.0 software (Stata corporation, College Station, Texas, USA). RESULTS: Thirteen studies met all inclusion criteria and were included in the analysis. In total, these studies included 13,751 patients. Of the patients, 8444 of them underwent neurosurgical clipping, and 5307 underwent endovascular coiling. The overall result of a pooled estimate revealed there was no statistically significant risk of shunt dependency difference between the clipping and coiling groups (11.4% vs. 12.0%, respectively; relative risk [RR], 0.92; 95% confidence interval [CI], 0.84-1.01). Six prospective studies (n = 1373) reported shunt-dependent hydrocephalus revealed no significant difference between clipping and coiling (23.3% vs. 20.1%, respectively; RR, 1.12; 95% CI, 0.91-1.38). Seven retrospective studies (n = 12,378) reported shunt-dependent hydrocephalus found statistical significance between the surgical and endovascular treatment groups (10.0% vs. 11.1%, respectively; RR, 0.88; 95% CI, 0.79-0.98). CONCLUSIONS: Microsurgical clipping and endovascular coiling of ruptured cerebral aneurysms are associated with similar incidences of ventricular shunt placement for hydrocephalus. The risk of shunt-dependent hydrocephalus is not higher after coiling than after clipping of ruptured intracranial aneurysms.

Loss of Shp2 within radial glia is associated with cerebral cortical dysplasia, glial defects of cerebellum and impaired sensory­motor development in newborn mice.

Radial glia are key neural progenitors involved in the development of the central nervous system. Tyrosine-protein phosphatase non­receptor type 11 (Shp2) is a widely expressed intracellular enzyme with multiple cellular functions. Previous studies have revealed the critical role of Shp2 in a variety of neural cell types; however, further investigation into the function of Shp2 within radial glia is required. In the present study, a conditional knockout mouse was generated using a human glial fibrillary acidic protein (hGFAP)­Cre driver, in which the Shp2 genes were deleted within radial glia. Loss of Shp2 within radial glia was associated with developmental retardation, postnatal lethality, reduced brain size and thinner cerebral cortices in newborn mice. Deletion of Shp2 also led to an increase in gliogenesis, a reduction in neural genesis and extracellular signal­regulated kinase signaling within the cerebral cortex. Furthermore, glial cell defects within the cerebellum of Shp2 mutants were observed, with abnormal granular cell retention and glial cell alignment in the external granular layer. In addition, Shp2 mutants exhibited impaired sensory­motor development. The results of the present study suggested that Shp2 may have an important role within radial glia, and regulate cerebral cortical and cerebellar development in newborn mice.