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Published on: November 18, 2010
Cerebral malaria-using the retina to study the brain
1Department of Eye and Vision Science, University of Liverpool, Liverpool, L7 8TX, UK. nbeare@liverpool.ac.uk.
Insights
Cerebral malaria (CM) in African children can be diagnosed and prognosed using malarial retinopathy signs. Retinal imaging reveals distinct mechanisms for death and neurological sequelae in CM.
Area of Science:
- Ophthalmology
- Neurology
- Infectious Diseases
Background:
- Cerebral malaria (CM) causes significant child mortality in Africa.
- Malarial retinopathy offers diagnostic and prognostic insights into CM.
- The retina serves as a window into the brain's pathophysiology during CM.
Purpose of the Study:
- To investigate the pathophysiology of CM using retinal imaging.
- To differentiate mechanisms leading to death versus neurological sequelae in CM.
- To explore the utility of OCT in identifying CM severity and outcomes.
Main Methods:
- Utilized fluorescein angiography and optical coherence tomography (OCT) to assess retinal changes in CM.
- Examined blood-retina barrier breakdown patterns (large focal, punctate, vessel leak).
- Correlated retinal findings with brain swelling and clinical outcomes (death, neurological sequelae).
Main Results:
- Patchy capillary non-perfusion and ischemic changes are common in CM retinas.
- Distinct blood-retina barrier breakdown types correlate with different outcomes: severe swelling/death (punctate/large focal leak) vs. moderate swelling/sequelae (vessel leak/non-perfusion).
- Death and neurological sequelae appear to have separate underlying mechanisms.
Conclusions:
- Malarial retinopathy provides crucial insights into CM pathophysiology.
- Retinal imaging can distinguish between mechanisms of fatal CM and those leading to neurological deficits.
- OCT of the optic nerve head and macula may aid in predicting severe brain swelling and neurological sequelae risk in CM.
Abstract:
Cerebral malaria (CM) remains a common cause of death of children in Africa with annual mortality of 400 000. Malarial retinopathy is a unique set of fundus signs which has diagnostic and prognostic value in CM. Assessment of malarial retinopathy is now widely utilised in clinical care, and routinely incorporated into clinical studies to refine entry criteria. As a visible part of the central nervous system, the retina provides insights into the pathophysiology of this infectious small-vessel vasculitis with adherent parasitised red blood cells. Fluorescein angiography and optical coherence tomography (OCT) have shown that patchy capillary non-perfusion is common and causes ischaemic changes in the retina in CM. It is likely this is mirrored in the brain and may cause global neurological impairments evident on developmental follow up. Three types of blood-retina barrier breakdown are evident: large focal, punctate, and vessel leak. Punctate and large focal leak (haemorrhage in formation) are associated with severe brain swelling and fatal outcome. Vessel leak and capillary non-perfusion are associated with moderate brain swelling and neurological sequelae. These findings imply that death and neurological sequelae have separate mechanisms and are not a continuum of severity. Each haemorrhage causes a temporary uncontrolled outflow of fluid into the tissue. The rapid accumulation of haemorrhages, as evidenced by multiple focal leaks, is a proposed mechanism of severe brain swelling, and death. Current studies aim to use optic nerve head OCT to identify patients with severe brain swelling, and macula OCT to identify those at risk of neurological sequelae.
