Improving cognitive outcome in cerebral malaria: insights from clinical and experimental research.
Cerebral Malaria (CM) is a clinical syndrome defined by the World Health Organization (WHO) as a potentially reversible diffuse encephalopathy characterized mainly by coma and the presence of asexual forms of Plasmodium falciparum parasites in peripheral blood smears in the absence of other causes of encephalopathy. A wide range of clinical manifestations follows the disease including cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM pathogenesis remain incompletely understood although vascular, immunological and metabolic changes have been described. The classical treatment of CM is based on the administration of antimalarial drugs, especially chloroquine and artemisinin derivates as artesunate. Even with treatment, 15 to 20% of children with CM die and approximately 10 to 17% of those who survive remain with significant long-term cognitive impairment. In this context, neuroprotective and adjuvant therapies have been recently investigated in clinical and experimental studies of CM in an attempt to improve cognitive outcome. A poor understanding of pathophysiological mechanisms, properties of compounds used and patient selection have contributed to the lack of success of these interventions. This review discusses clinical aspects of cognitive sequelae, possible mechanisms involved in the brain injury, perspectives and limitations regarding the pharmacological strategies to improve cognitive outcome in CM.
Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. alines.miranda@hotmail.com
Aline Silva
AS
de Miranda
Fátima
F
Brant
Fabiana Simão
FS
Machado
Milene Alvarenga
MA
Rachid
Antônio Lúcio
AL
Teixeira
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D035843:Biomedical Research / Q000379:methods* / Q000639:trends; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016779:Malaria, Cerebral / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
D000962:Antimalarials; D018696:Neuroprotective Agents