Table 1.

Manifestations of cerebral malaria in the retina and brain

		Paediatric retina	Paediatric brain	Adult brain
Sequestration	Frequency	Always present in fatal cerebral malaria (Lewallen et al., 2000). Unclear if absent in fatal coma of other cause or severe malarial anaemia.	Always present in fatal cerebral malaria, and absent in fatal coma of other cause (Taylor et al., 2004; Dorovini-Zis et al., 2011).	Always present in fatal cerebral malaria (MacPherson et al., 1985; Oo et al., 1987; Pongponratn et al., 1991; Sein et al., 1993).
			Commonly associated with sequestered leucocytes (Brown et al., 2001; Armah et al., 2005)	In cerebral malaria density is greater in brain than other organs (MacPherson et al., 1985; Pongponratn et al., 1991).
				Significant sequestration may be present in fatal non-cerebral malaria (MacPherson et al., 1985; Silamut et al., 1999).
				The percentage of vessels with sequestration is greater in cerebral malaria than non-cerebral malaria (Ponsford et al., 2012)
	Location	Patchy distribution within capillary network (Lewallen et al., 2000).	Most microvessels, and the margins of pial and larger vessels (Dorovini-Zis et al., 2011).	Occurs in capillaries, venules, and very occasional arterioles (MacPherson et al., 1985).
		Variation between retinal regions not yet defined.	Grey and white matter of cerebrum, subcortex, brainstem and cerebellum (Armah et al., 2005; Dorovini-Zis et al., 2011).	Occurs in grey and white matter, but most dense in cerebral white matter (Nagatake et al., 1992).
				Density reduces from cerebrum to cerebellum to brainstem (Pongponratn et al., 2003).
				Density greater in cerebellum than cerebrum (Sein et al., 1993).
	Vessels involved	Capillaries and margins of larger vessels (Lewallen et al., 2000).	Occurs in brain microvessels, pial and larger vessels (Dorovini-Zis et al., 2011)	Predominant site is the capillary bed, but also occurs in larger pial and subarachnoid vessels (Spitz, 1946).
		Vessel discolouration affects capillaries, venules, and arterioles (personal observation)		Uncommon in arterioles (MacPherson et al., 1985).
Haemorrhages	Type	White-centred, blot (White et al., 2001).	Ring (Dorovini-Zis et al., 2011).	Ring, perivascular (Spitz, 1946; Nagatake et al., 1992; Sein et al., 1993; Turner, 1997).
		Parasitized erythrocytes rarely seen outside vessel (White et al., 2001).	Parasitized erythrocytes rarely seen outside vessel (White et al., 2001; Dorovini-Zis et al., 2011).
				Parasitized erythrocytes are seen outside vessel (Sein et al., 1993; Turner, 1997).
	Frequency	Gross haemorrhages present in 78% fatal cerebral malaria, 7% fatal coma of other cause (White et al., 2009).	Any type present in 80% fatal cerebral malaria (Dorovini-Zis et al., 2011).	Ring haemorrhages present in up to 30% of cases of fatal cerebral malaria (Spitz, 1946).
				No significant difference in haemorrhage frequency between cerebral malaria (∼60% of cases) and non-cerebral malaria (∼40% of cases) (Medana et al., 2011).
	Location	All retinal quadrants. Usually restricted to inner retinal layers, with extension to subretinal haemorrhage in severe cases (White et al., 2009).	Common in white matter, rare in grey matter except in the cerebellum (White et al., 2001; Dorovini-Zis et al., 2011).	Usually occur in cerebral white matter; also reported in pons, medulla, cerebellum, and cortical grey matter (Spitz, 1946; Nagatake et al., 1992; Sein et al., 1993; Turner, 1997).
				No difference in haemorrhage frequency between cortex, diencephalon, and brainstem (Medana et al., 2011).
Vessel leakage	Type	Fibrinogen leakage along vessels with and without associated haemorrhage (White et al., 2009).	Fibrinogen leakage often associated with haemorrhage, can be independent of haemorrhage (Dorovini-Zis et al., 2011).	Rarefaction of the perivascular space, perivascular pools of proteinaceous material, vacuolar parenchymal oedema, oedema between fibres of white matter tracts, fluid-filled spaces between myelin fibres. No difference between fatal cerebral and non-cerebral malaria (Medana et al., 2011).
	Frequency	Fibrinogen leakage in 31 % cases fatal cerebral malaria, 7% fatal coma of other cause (White et al., 2009).	Unclear how many cases of fatal cerebral malaria have leakage of any type.	At least one type of oedema present in all cases of both cerebral and non-cerebral malaria (Medana et al., 2011).
		Average (SD) number of foci is 1.2 (2.6) in fatal cerebral malaria and 0.21 (1.1) in coma of other cause (White et al., 2009).	Leakage greater in white than grey matter (associated with haemorrhages) (Dorovini-Zis et al., 2011).	Oedema between white matter tract fibres is most common in: brainstem > diencephalon > cortex (Medana et al., 2011).
	Location/vessels involved	Associated with vessels but not defined in terms of retinal quadrants or vessel type (White et al., 2009).	Cerebral white and grey matter, subcortex, brainstem and cerebellum (Dorovini-Zis et al., 2011).	Brainstem, diencephalon, cerebral cortex (Medana et al., 2011).
		Angiographic fluorescein leakage predominantly affects venules (Beare et al., 2009).
Regions vulnerable to presumed ischaemia on imaging		Retinal whitening and capillary non-perfusion appears to be especially prominent at the foveal avascular zone, horizontal raphe, and retinal periphery. All are watershed regions (Beare et al., 2009).	Regions where MRI brain signal changes distinguish between retinopathy-positive and negative cerebral malaria (highest to lowest odds ratio): basal ganglia, corpus callosum, cerebral cortex, thalamus, cerebral white matter, posterior fossa (Potchen et al., 2012).	Regions reported to be involved: Brain stem, thalamus, cerebellum, corpus callosum, cerebral white matter (Yadav et al., 2008; Rasalkar et al., 2011).