Diffuse, non-traumatic, non-aneurysmal subarachnoid haemorrhage during bevacizumab treatment of high grade glioma: case report and review of the literature

• First report of diffuse subarachnoid haemorrhage of no other cause during bevacizumab therapy.
• No current consensus on the risk of Central Nervous System haemorrhage during bevacizumab therapy.
• Promotion of vessel defects, vasoconstriction and hypertension are likely causative mechanisms.
• Clinicians should be cognisant of this potential adverse effect while further studies are awaited.

Background: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor approved by the United States Food and Drug Administration for the treatment of various cancers including refractory high grade glioma. There are case reports of subarachnoid haemorrhage (SAH) during bevacizumab treatment though the causative role of the drug in these cases has been obscured by the presence of alternative aetiologies or incomplete investigation. Furthermore, there is no consensus regarding the risk of Central Nervous System (CNS) haemorrhage during bevacizumab treatment due to limited available study data. Case Description: A 53 year old female with recurrent gliosarcoma refractory to standard, temozolamide based chemo-radiotherapy presented to our facility in a post-ictal state 16 days after her second dose of intravenous bevacizumab. A Fisher grade III SAH was found on computerised tomography scanning with no causative vascular lesion found on two subsequent digital subtraction angiograms separated by a 10 day period and a Magnetic Resonance Imaging (MRI) scan 20 days post-bleed. Given the resolution of symptoms over an uncomplicated 13 day admission, she was discharged home with bevacizumab ceased prior to her scheduled third dose. Conclusion: We discuss here a case of diffuse, non-traumatic SAH during bevacizumab treatment of recurrent gliosarcoma in which alternative aetiologies of haemorrhage were excluded, to our knowledge the first such case in the English language literature. This adverse event is compatible with the known molecular mechanisms of bevacizumab and clinicians should be cognisant of the potential risk of CNS haemorrhage until larger studies are available to quantify this risk.