Apnea as an uncommon preoperative manifestation of medulla cavernous malformation: surgical treatment and literature review.

OBJECTIVE: Apnea is not a common preoperative manifestation of medulla cavernous malformations (CMs). The role of surgical resection in patients suffering from apnea secondary to hemorrhage from medulla CMs requires further definition. METHODS: Medical records and radiographs were reviewed retrospectively for four patients treated surgically for medulla CMs in our institution between 2008 and 2011. Recent outcomes for these patients were also evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. RESULTS: All four patients (3 male, 1 female; mean age: 41.3 years) suffered two or three hemorrhages with a preoperative mRS of five and, due to the loss of autonomous respiration and consciousness, underwent a preoperative tracheotomy for mechanical ventilation, which lasted an average of 4.5 days. Prior to surgery, all patients had recovered to the point of maintaining spontaneous breath and normal blood gas values with oxygen supplementation. Lesions were totally resected in all patients via the posterior suboccipital approach. Postoperative ventilation was continued in one patient for 1 day. The mean postoperative mRS score at discharge was 3.5, and all patients had improved from their previous scores. The tracheostomy was closed in three patients at 15, 16, and 35 days after surgery. After a mean follow-up of 34.7 months, the most recent mRS scores were 3, 2, 2, and 2; no recurrent hemorrhage was noted, and three patients lived independently. CONCLUSION: In carefully selected patients with hemorrhage due to medulla CMs, favorable outcomes can be achieved even if apnea was a part of the preoperative clinical presentation. Surgery should be considered in these patients, particularly in those with repeated hemorrhages, and apnea should not be considered an absolute contraindication to surgery.

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study.

Objective: Hypoxia-inducible factor 1alpha (HIF-1α) functions as a crucial transcriptional mediator in hypoxic and ischemic brain response. We endeavored to assess the prognostic significance of serum HIF-1α in human aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, longitudinal, multicenter, and observational study of 257 patients with aSAH and 100 healthy controls, serum HIF-1α levels were quantified. Univariate analyses, followed by multivariate analyses, were performed to discern the relationship between serum HIF-1α levels and severity and delayed cerebral ischemia (DCI) plus poststroke 6-month poor outcome [extended Glasgow outcome scale (GOSE) scores of 1-4]. Predictive efficiency was determined under the receiver operating characteristic (ROC) curve. Results: There were significantly increased serum HIF-lα levels after aSAH, in comparison to controls (median, 288.0 vs. 102.6 pg/ml; P < 0.001). Serum HIF-lα levels were independently correlated with Hunt-Hess scores [ß, 78.376; 95% confidence interval (CI): 56.446-100.305; P = 0.001] and modified Fisher scores (ß, 52.037; 95% CI: 23.461-80.614; P = 0.002). Serum HIF-lα levels displayed significant efficiency for discriminating DCI risk [area under ROC curve (AUC), 0.751; 95% CI: 0.687-0.815; P < 0.001] and poor outcome (AUC, 0.791; 95% CI: 0.736-0.846; P < 0.001). Using the Youden method, serum HIF-1α levels >229.3 pg/ml predicted the development of DCI with 92.3% sensitivity and 48.4% specificity and serum HIF-1α levels >384.0 pg/ml differentiated the risk of a poor prognosis with 71.4% sensitivity and 81.1% specificity. Serum HIF-1α levels >229.3 pg/ml were independently predictive of DCI [odds ratio (OR), 3.061; 95% CI: 1.045-8.965; P = 0.041] and serum HIF-1α levels >384.0 pg/ml were independently associated with a poor outcome (OR, 2.907; 95% CI: 1.403-6.024; P = 0.004). The DCI predictive ability of their combination was significantly superior to those of Hunt-Hess scores (AUC, 0.800; 95% CI: 0.745-0.855; P = 0.039) and modified Fisher scores (AUC, 0.784; 95% CI: 0.726-0.843; P = 0.004). The prognostic predictive ability of their combination substantially exceeded those of Hunt-Hess scores (AUC, 0.839; 95% CI: 0.791-0.886; P < 0.001) and modified Fisher scores (AUC, 0.844; 95% CI: 0.799-0.890; P < 0.001). Conclusion: Elevated serum HIF-lα levels after aSAH, in independent correlation with stroke severity, were independently associated with DCI and 6-month poor outcome, substantializing serum HIF-lα as a potential prognostic biomarker of aSAH.

Serum netrin-1 concentrations are associated with clinical outcome in acute intracerebral hemorrhage.

BACKGROUND: Netrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. METHODS: This study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: ICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. CONCLUSIONS: Serum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.

Determination of serum neutrophil gelatinase-associated lipocalin as a prognostic biomarker of acute spontaneous intracerebral hemorrhage.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is currently known as an acute phase protein and implicated in acute brain injury. Herein, we sought to gauge serum NGAL level in patients after acute (<24 h) spontaneous intracerebral hemorrhage (ICH) and to investigate its relation to neurological outcome. METHODS: Serum NGAL levels were measured in 106 patients and 106 controls. National Institutes of Health Stroke Scale (NIHSS) score, Glasgow coma scale (GCS) score, ICH score and hematoma volume were recorded for assessing hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: As opposed to the controls, the patients had significantly raised serum NGAL levels. Correlations were observed between NGAL levels and serum C-reactive protein levels, blood glucose levels, GCS score, NIHSS score, ICH score and ICH volume. Multivariate analysis identified serum NGAL as a predictor for unfavorable outcome at 90 days. It also showed high prognostic ability under receiver operating characteristic curve. CONCLUSIONS: Enhanced NGAL level is revealed after acute spontaneous ICH, in association with inflammatory degree and hemorrhagic severity, and intimately correlated with a worse prognosis.

Optimal timing of dopamine agonist withdrawal in patients with hyperprolactinemia: a systematic review and meta-analysis.

PURPOSE: Dopamine agonists (DAs) are recommended as first-line treatment for patients with hyperprolactinemia. Generally, it is accepted that patients with hyperprolactinemia do not need lifelong medication, but the optimal timing for DA withdrawal has not been determined. The aim of this systematic review and meta-analysis is to assess the impact of DA withdrawal on the clinical outcomes of patients with hyperprolactinemia, and to explore possible factors affecting successful DA withdrawal. METHODS: The databases of PubMed, Cochrane and EMBASE were searched up to May 2016. RESULTS: The proportion of patients with persisting normoprolactinemia after DA withdrawal reached 36.6% in a random effects model (95% CI, 29.4-44.2%; I-squared: 82.5%). Data of stratified analysis showed that the success rate of drug withdrawal was high in patients using cabergoline (CAB) as the only treatment (41.2%; 95% CI 32.3-50.4%) and those using CAB over 24 months (48.7%; 95% CI 38.9-58.5%), especially in patients with idiopathic hyperprolactinemia (73.2%; 95% CI 55.6-87.7%). In addition, patients who received a low maintenance dose of CAB, and had a significant reduction in tumor size (over 50%) before withdrawal, were more likely to achieve success (51.5 and 49.4%, respectively). CONCLUSION: The success rate of DA withdrawal has increased in recent years. Further, the success rate of CAB withdrawal was higher than that of bromocriptine, especially in patients with a duration of treatment longer than 24 months. Conclusively, the probability of success was higher in patients who received low-dose CAB maintenance treatment and those who achieved a significant reduction in tumor size before withdrawal.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133(+) and CD133(-) cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133(+) cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133(-) cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133(+) astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133(-) astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.