Publication: Coma in fatal adult human malaria is not caused by cerebral oedema
Accepted Date
2011-09-17
Issued Date
2011-09-17
Copyright Date
2011
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Medana IM, Day NP, Sachanonta N, Mai NT, Dondorp AM, Pongponratn E, et al. Coma in fatal adult human malaria is not caused by cerebral oedema. Malar J. 2011 Sep 17;10:267.
Suggested Citation
Medana, Isabelle M., Day, Nicholas P.J., Navakanit Sachanonta, นวขนิษฐ์ สัจจานนท์, Mai, Nguyen T.H., Dondorp, Arjen M., Emsri Pongponratn, เอี่ยมศรี พงศ์พนรัตน์, Hien, Tran T., White, Nicholas J., Turner, Gareth D.H. Coma in fatal adult human malaria is not caused by cerebral oedema. Medana IM, Day NP, Sachanonta N, Mai NT, Dondorp AM, Pongponratn E, et al. Coma in fatal adult human malaria is not caused by cerebral oedema. Malar J. 2011 Sep 17;10:267.. doi:10.1186/1475-2875-10-267. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/716
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Title
Coma in fatal adult human malaria is not caused by cerebral oedema
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Abstract
BACKGROUND: The role of brain oedema in the pathophysiology of cerebral malaria
is controversial. Coma associated with severe Plasmodium falciparum malaria is
multifactorial, but associated with histological evidence of parasitized
erythrocyte sequestration and resultant microvascular congestion in cerebral
vessels. To determine whether these changes cause breakdown of the blood-brain
barrier and resultant perivascular or parenchymal cerebral oedema, histology,
immunohistochemistry and image analysis were used to define the prevalence of
histological patterns of oedema and the expression of specific molecular pathways
involved in water balance in the brain in adults with fatal falciparum malaria.
METHODS: The brains of 20 adult Vietnamese patients who died of severe malaria
were examined for evidence of disrupted vascular integrity. Immunohistochemistry
and image analysis was performed on brainstem sections for activation of the
vascular endothelial growth factor (VEGF) receptor 2 and expression of the
aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed
as evidence of blood-brain barrier leakage and perivascular oedema formation.
Correlations were performed with clinical, biochemical and neuropathological
parameters of severe malaria infection.
RESULTS: The presence of oedema, plasma protein leakage and evidence of VEGF
signalling were heterogeneous in fatal falciparum malaria and did not correlate
with pre-mortem coma. Differences in vascular integrity were observed between
brain regions with the greatest prevalence of disruption in the brainstem,
compared to the cortex or midbrain. There was a statistically non-significant
trend towards higher AQP4 staining in the brainstem of cases that presented with
coma (P = .02).
CONCLUSIONS: Histological evidence of cerebral oedema or immunohistochemical
evidence of localised loss of vascular integrity did not correlate with the
occurrence of pre-mortem coma in adults with fatal falciparum malaria. Enhanced
expression of AQP4 water channels in the brainstem may, therefore, reflect a mix
of both neuropathological or attempted neuroprotective responses to oedema
formation.