Management and monitoring strategies for severe cerebral malaria: a guide for the intensivist

Abstract

Severe malaria, caused by Plasmodium falciparum, poses a critical public health challenge, with cerebral malaria (CM) representing its most severe and life-threatening neurological manifestation. Defined by impaired consciousness (Glasgow Coma Score < 11) after the exclusion of other causes of encephalopathy, CM remains a critical condition with a mortality rate of 15-25% and long-term neurological sequelae in survivors. CM pathogenesis involves parasitized erythrocyte sequestration in cerebral microvasculature, immune hyperactivation, blood-brain barrier disruption, and cerebral edema, potentially leading to elevated intracranial pressure (ICP) and cerebral ischemia. These processes culminate in severe neurological injury, emphasizing the importance of ICP management in minimizing secondary brain damage. Neuromonitoring (NM) strategies, including invasive and non-invasive techniques, are critical yet underutilized in adults with CM due to limited evidence and logistical challenges. Treatment relies on antimalarial therapy, with intravenous artesunate as the first-line drug, supported by targeted interventions to manage seizures and systemic complications. Adjunctive therapies remain experimental, with no proven benefit in routine care. Emerging evidence from pediatric studies offers valuable insights, though significant gaps in adult-focused research persist. This review, which examines severe CM pathophysiology, clinical manifestations, and management, focusing on adult populations, underscores the need for tailored NM approaches, protocolized management strategies, and further investigation to improve outcomes in adults with CM, advocating for a multidisciplinary approach within the intensive care setting.

Keywords: Adjuvant; Anticonvulsants; Artesunate; Biomarkers; Blood-brain barrier; Cerebral; Chemotherapy; Critical care; Electroencephalography; Intracranial hypertension; Malaria; Seizures.

Fig. 1

Main mechanisms involved in the pathogenesis of cerebral malaria. (1) Flow disturbances caused by sequestration of infected erythrocytes (IE) in capillaries; (2) Excessive cytokine production; (3) Brain blood barrier (BBB) damage; (4) Cerebral Edema and increased intracranial pressure (ICP). DIC disseminated intravascular coagulation

Fig. 2

Brain imaging in cerebral malaria. Cerebral CT-scan (A) and Magnetic Resonance Imaging (MRI) Fluid Attenuated Inversion Recovery (FLAIR - B) sequences showing diffuse involvement of the white matter, thalamus and globus pallidus, in a patient with cerebral malaria

Fig. 3

Multimodal risk stratification for intracranial hypertension in cerebral malaria. GCS Glasgow Coma Scale, BFV blood flood velocity, dBFV diastolic blood flow velocity. Focal deficits may not be present in the context of increased intracranial pressure due to global edema and diffuse injury

Fig. 4

Management of severe malaria. In case of neuroworsening, monitoring of systemic variables (GHOST-CAP) is also mandatory