Elevated Intracranial Pressure in Cryptococcal Meningoencephalitis: Examining Old, New, and Promising Drug Therapies

Abstract

Despite the availability of effective antifungal therapy, cryptococcal meningoencephalitis (CM) remains associated with elevated mortality. The spectrum of symptoms associated with the central nervous system (CNS) cryptococcosis is directly caused by the high fungal burden in the subarachnoid space and the peri-endothelial space of the CNS vasculature, which results in intracranial hypertension (ICH). Management of intracranial pressure (ICP) through aggressive drainage of cerebrospinal fluid by lumbar puncture is associated with increased survival. Unfortunately, these procedures are invasive and require specialized skills and supplies that are not readily available in resource-limited settings that carry the highest burden of CM. The institution of pharmacologic therapies to reduce the production or increase the resorption of cerebrospinal fluid would likely improve clinical outcomes associated with ICH in patients with CM. Here, we discuss the potential role of multiple pharmacologic drug classes such as diuretics, corticosteroids, and antiepileptic agents used to decrease ICP in various neurological conditions as potential future therapies for CM.

Severe meningoencephalitis: epidemiology and outcomes

“…A recent multicenter trial showed that single-dose liposomal Amphotericin B (10 mg/kg/day) on day-1 plus 14 days of flucytosine (100 mg/kg/day) and fluconazole (1200 mg/day) could represent an interesting therapeutic option, as compared with the current WHO-recommended regimen, which includes amphotericin B deoxycholate (1 mg/kg/ day) plus flucytosine (100 mg/kg/day) for 7 days, followed by fluconazole (1200 mg/day) for 7 days [34]. The key point in ICU is the management of raised intracranial pressure (ICP) through aggressive drainage of CSF by lumbar puncture, which is associated with increased survival [35]. The potential role of multiple pharmacologic drug classes such as diuretics, corticosteroids, and antiepileptic agents used to decrease ICP in various neurological conditions remain unclear for cryptococcal meningoencephalitis [35].…”

“…The key point in ICU is the management of raised intracranial pressure (ICP) through aggressive drainage of CSF by lumbar puncture, which is associated with increased survival [35]. The potential role of multiple pharmacologic drug classes such as diuretics, corticosteroids, and antiepileptic agents used to decrease ICP in various neurological conditions remain unclear for cryptococcal meningoencephalitis [35].…”