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Glibenclamide in aneurysmal subarachnoid hemorrhage: a randomized controlled clinical trial

Bruno Braga Sisnando da Costa, Isabela Costola Windlin, Edwin Koterba, Vitor Nagai Yamaki, Nícollas Nunes Rabelo, Davi Jorge Fontoura Solla, Antonio Carlos Samaia da Silva Coelho, João Paulo Mota Telles, Manoel Jacobsen Teixeira, and Eberval Gadelha Figueiredo


Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide’s impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH).


Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS).


A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2–4), 3 (IQR 3–4), and 3 (IQR 1–4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29–1.48], adjusted common OR 1.25 [95% CI 0.46–3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0–2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%).


In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.

Open access

Human herpesvirus DNA occurrence in intracranial aneurysmal wall: illustrative case

Nícollas Nunes Rabelo, Antonio Carlos Samaia da Silva Coelho, João Paulo Mota Telles, Giselle Coelho, Caio Santos de Souza, Tania Regina Tozetto-Mendoza, Natan Ponzoni Galvani de Oliveira, Paulo Henrique Braz-Silva, Manoel Jacobsen Teixeira, and Eberval Gadelha Figueiredo


Subarachnoid hemorrhages secondary to intracranial aneurysms (IAs) are events of high mortality. These neurological vascular diseases arise from local and systemic inflammation that culminates in vessel wall changes. They may also have a possible relationship with chronic viral infections, such as human herpesvirus (HHV), and especially Epstein–Barr virus (EBV), which causes several medical conditions. This is the first description of the presence of HHV deoxyribonucleic acid (DNA) in a patient with IA.


A 61-year-old woman with a downgraded level of consciousness underwent radiological examinations that identified a 10-mm ruptured aneurysm in the anterior communicating artery. A microsurgery clip was performed to definitively treat the aneurysm and occurred without surgical complications. Molecular analysis of the material obtained revealed the presence of EBV DNA in the aneurysm wall. The patient died 21 days after admission due to clinical complications and brain swelling.


This is the first description of the presence of herpesvirus DNA in a patient with IA, presented in 2.8% of our data. These findings highlight that viral infection may contribute to the pathophysiology and is an additional risk factor for IA formation, progression, and rupture by modulating vessel wall inflammation and structural changes in chronic infections.