Abstract 090: Delayed Cerebral Vasculopathy as a Complication of Pneumococcal Meningitis

Abstract

Introduction Pneumococcal meningitis is a severe neuro‐infectious disease with high mortality rates and long‐term neurological complications. Amongst these complications is the delayed cerebral vasculopathy (DCV) which develops days to weeks into the disease course, is characterized by multifocal arterial narrowing resulting in cerebral infarctions. In this abstract, we discuss the challenging aspect of managing pneumococcal meningitis complicated by DCV and providing an overview of potential pathophysiological mechanisms to delineate potential avenues for future treatment strategies. Methods We present a case of DCV leading to multiple cerebral infarctions in a 66‐year‐old male patient admitted for pneumococcal meningitis and not treated with empiric dexamethasone. Milrinone was utilized in this patient with radiographic improvement. Results DCV is a rare but serious complication of acute bacterial meningitis (ABM), affecting approximately 4% of cases. The underlying etiology and risk factors remain unclear due to the limited number of reported cases and the incomplete understanding of the underlying mechanisms. Previously, DCV was attributed solely to para‐infectious vasculitis, but recent studies suggested other possible mechanisms. Potential risk factors of DCV include recurrent fever, intensive care unit admission, lower CSF WBC count, and high CSF bacterial load. The suggested DCV pathophysiologic mechanisms involve vascular inflammation and delayed cerebral thrombosis (DCT). The release of bacterial wall components, cell surface proteins, free radicals, and pro‐inflammatory cytokines including IL‐1, TNF, IL‐6, IL‐8, and macrophage inflammatory protein might lead to para‐infectious vasculitis disrupting the blood‐brain barrier, which might cause vessel wall weakening and cerebral microhemorrhages. Post‐infectious vasculitis triggered by a delayed autoimmune response with the production of autoantibodies is another proposed mechanism. DCT, triggered a C5a‐mediated thrombotic response, is suggested to contribute to cerebral infarctions in ABM patients as C5a can induce expression of plasminogen‐activator inhibitor 1 and up‐regulate tissue factor, initiating the coagulation cascade and amplifying the thrombotic response. Due to the unclear pathophysiology and lack of data, treatment options are limited. The role of dexamethasone in the development of DCV remains controversial as some reports suggested it may increase the incidence of vasospasm/vasculitis, and thrombosis, while others suggested dexamethasone as a treatment for DCV. Currently, there is no consensus regarding the use of dexamethasone in DCV and remains an area that requires further research to establish their optimal use and potential risks. Intra‐arterial and intrathecal vasodilators have been reportedly used with variable outcomes. Intra‐arterial and intravenous Milrinone, a phosphodiesterase‐3 inhibitor, showed benefits in subarachnoid hemorrhage‐associated vasospasm, and it was used in DCV with observed benefits. In our case, we initiated Milrinone for two days, and interestingly, an improvement in the vasospasm was noted (Figure 1). However, there was no changes in the clinical outcome in our case. Conclusion There is a need for further research into the complex etiology of DCV in ABM. The benefits of corticosteroids require careful consideration in managing this serious complication. Intravenous Milrinone has shown promise, although limited to case reports. Other treatment avenues, such as targeting matrix metalloproteinases and C5a are still theoretical. The use of intra‐arterial and endovascular options has not been fully studied.