title: The evidence for a role of vasospasm in the pathogenesis of cerebral malaria.
abstract: Due to delay in treatment, cerebral malaria (CM) remains a significant complication of Plasmodium falciparum infection and is a common cause of death from malaria. In addition, more than 10 % of children surviving CM have neurological and long-term cognitive deficits. Understanding the pathogenesis of CM enables design of supportive treatment, reducing neurological morbidity and mortality. Vaso-occlusion and brain swelling appear to be leading to clinical features, neuronal damage and death in CM. It is proposed that parasitized red blood cells (pRBC), due to cytoadhesion to the endothelium and vasospasm induced by reduced bioavailability of nitric oxide, are causes. Stasis of blood flow and accumulation of pRBC may allow, after schizont rupture, for high concentration of products of haemolysis to accumulate, which leads to localized nitric oxide depletion, inducing adhesion molecules and cerebral vasospasm. Features consistent with an involvement of vasospasm are rapid reversibility of neurological symptoms, intermittently increased or absent flow in medium cerebral artery detectable on Doppler ultrasound and hemispheric reversible changes on cerebral magnetic resonance imaging in some patients. Clinical trials of treatment that can rapidly reduce cerebral vasospasm, including nitric oxide donors, inhaled nitric oxide, endothelin or calcium antagonists, or tissue plasminogen activators, are warranted.
authors.affiliation: Luton and Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton, LU4ODZ, UK. michael_eisenhut@yahoo.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
mesh_terms: D000818:Animals; D006801:Humans; D016779:Malaria, Cerebral / Q000209:etiology* / Q000473:pathology*; D016778:Malaria, Falciparum / Q000150:complications* / Q000473:pathology*; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000473:pathology*