Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Short-term tranexamic acid treatment reduces in-hospital mortality in aneurysmal sub-arachnoid hemorrhage: A multicenter comparison study.

BACKGROUND: Recurrent bleeding is one of the major causes of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Antifibrinolytic therapy is known to reduce recurrent bleeding, however, its beneficial effect on outcome remains unclear. The effect of treatment with tranexamic acid (TXA) until aneurysm treatment on clinical outcome is evaluated. METHODS: Patients with an aSAH from two high-volume tertiary referral treatment centers in the Netherlands, Academic Medical Center (AMC) and Radboud University Medical Center (RUMC), between January 2012 and December 2015 were included. Patients were classified into one of two groups; standard treatment or TXA treatment. Demographic and clinical characteristics, in-hospital complications and clinical outcome were compared between the two groups. Multivariate logistic regression was used to adjust for the influence of treatment center and baseline differences. RESULTS: Standard treatment was given in 509 patients, and 119 patients received additional TXA therapy before aneurysm occlusion. Patients treated with TXA did not experience less recurrent bleeding adjusted or unadjusted for treatment center (adjusted odds ratio [aOR] 0.80, 95% confidence interval [95% CI]: 0.37-1.73). In-hospital mortality, was significantly lower in the TXA group than the standard care group (adjusted OR [aOR] 0.42, 95% CI: 0.20-0.85). Poor outcome (mRS 4-6) assessed after six months was not different between treatment groups (aOR 1.05, 95% CI: 0.64-1.74). CONCLUSIONS: Pooled data from two high-volume treatment centers did not show improved clinical outcome after additional TXA treatment in aSAH patients. However, TXA treatment was associated with a decrease in mortality.

Time intervals from subarachnoid hemorrhage to rebleed.

The most threatening early complication and predictor of poor outcome after an aneurysmal subarachnoid hemorrhage (aSAH) is a rebleed. To evaluate what proportion of rebleeds might be prevented by early treatment, we assessed the time interval from the initial hemorrhage to rebleed, and the location of the patient at the time of rebleed. Patient characteristics, World Federation of Neurological Surgeons grade on admission and modified Rankin Scale outcome scores, referring hospitals and time intervals from initial hemorrhage to treatment of 293 patients treated between 2008 and 2011 were evaluated. Time intervals to rebleeds and location of the patients at the time of rebleed were retrieved. Rebleeds were confirmed by CT in 12% of patients, and an additional 4% of patients was diagnosed as having a possible rebleed. Sixty percent of rebleeds occurred after admission to the treatment center. Almost all rebleeds occurred within 24 h, with a median time interval between initial hemorrhage and rebleed of 180 min. A significantly shorter time to treatment and a higher mortality were seen in the group of patients with a rebleed. Approximately, one in six patients with an aSAH had a rebleed, of which a majority might have been preventable because they occurred after admission to the treatment center. A reduction in the rebleed rate seems feasible by securing the aneurysm as soon as possible by improving in-hospital logistics for early aneurysm treatment. Alternative options, such as immediate administration of antifibrinolytics, are being explored in a multicenter trial.

Spinal vascular malformations in non-perimesencephalic subarachnoid hemorrhage.

OBJECTIVE: In patients with non-traumatic subarachnoid hemorrhage (SAH) and no evidence for a cerebral aneurysm on angiography, a frequent cause of the hemorrhage is perimesencephalic hemorrhage or other cerebral vascular pathology. In some patients no cause is found. The exact incidence of a spinal vascular malformation (SVM) as the origin for the SAH is not known. We assessed the occurrence of SVM in angiogram-negative, non-perimesencephalic subarachnoid hemorrhage (NPSAH). METHODS: 47 patients (from a consecutive cohort of 632) were identified with an angiogramnegative, non-perimesencephalic subarachnoid hemorrhage and 42 of these were analyzed by performing MR-imaging of the complete spinal neuraxis with additional spinal angiography on indication. RESULTS: In four patients a spinal vascular malformation was identified as the cause of the SAH, indicating an incidence of 9 % of SVM in NPSAH, and an incidence of 1 % of SVM in all patients with SAH. INTERPRETATION: Systematic analysis of angiogram-negative, non-perimesencephalic subarachnoid hemorrhage by MR imaging of the complete spinal neuraxis yields a higher incidence of SVM than previously documented. We recommend MR imaging of the complete spinal neuraxis in patients with a non-perimesencephalic subarachnoid hemorrhage in whom no cause for the hemorrhage has been found.