Predicting acute and post-recovery outcomes in cerebral malaria by Optical Coherence Tomography
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Date
2022-06-02
Authors
Journal Title
Journal ISSN
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Publisher
Kamuzu University of Health Sciences
Abstract
Type of study
This is an observational cohort study of children with cerebral malaria (CM) and other comas
conducted at a single-site. We will assess ocular imaging techniques as methods to identify
severe brain swelling during the acute illness, and predict neurodevelopmental deficits after
CM.
Problem
Children in Africa continue to die in large numbers from CM, mostly with severe brain swelling.
New treatments for severe brain swelling and to reduce intracranial pressure (ICP) in CM are
under clinical trial, but rely on MRI scans to identify severe brain swelling. Hardly any children
with CM have access to MRI scanning, so those likely to benefit from new treatments are not
identifiable. Children in coma for other causes would also benefit from the identification of
raised intracranial pressure.
Children who survive CM are at high risk of neurological and developmental complications. It
is thought that this may be due to cerebral ischaemia but at present there is no method to
identify these children other than waiting for their deficit to become manifest. Identifying CM
patients at risk of neurological deficit or developmental delay would enable early intervention.
Identifying a link between cerebral ischaemia and neurodevelopmental deficit (NDD) would
also support the development of new treatments for CM which mitigate ischaemic injury.
Optical Coherence Tomography (OCT) is a non-invasive ocular imaging modality which uses
low-coherence light to obtain detailed cross-sectional images of the retina and optic nerve
head (ONH). The ONH swells with raised intracranial pressure (papilloedema).
Objectives
Broad objective
To develop an OCT based bedside test to identify and quantify brain swelling in CM and other
comas, and predict NDD in CM.
Specific objectives
1. To determine the accuracy of OCT measures of ONH swelling to detect severe brain
swelling in children with CM compared to brain MRI.
2. To ascertain the accuracy of OCT measures of macular ischaemia to predict NDD in
children with CM at 1 and 2 years post-recovery.
3. To establish if large accumulation of retinal haemorrhages predicts progression to severe
brain swelling in children with CM.
4. To determine if OCT measures of ONH swelling can detect and quantify raised ICP in other
comas in children.
5. To establish if a low-cost handheld OCT with AI analytics and tested to ISO standard can
replace the commercially available OCT and human image analysis.
Methodology
Participants will be recruited on admission with CM and other comas. During the acute illness
participants will have OCT of the ONH and macula, and fundus imaging, in addition to
standard care which includes funduscopy and an MRI brain scan. Children with CM will be
followed up over 2 years with OCT, MRI and neurodevelopmental assessments.
We will test the value of OCT-measured ONH parameters to identify severe brain swelling
determined by MRI (gold standard). We will use Receiver Operating Characteristic (ROC)
curves to determine the utility of OCT of the ONH to identify severe brain swelling, and which
parameter(s) have the best specificity and sensitivity.OCT in CM. Version 32.0. Date 14th 2nd Mayrch 2022 6 of 20
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OCT of the retina can identify retinal ischaemia manifest as hyper-reflective signal. Similar
statistical methods will be employed to determine the value of OCT of the central retinal
(macula) to identify patients developing NDD (either at discharge or during follow up). Children
will have Malawi Developmental Assessment Tool (MDAT)(<5yrs) or Kaufman Assessment
Battery for Children (ABC)(>5yrs) developmental assessment as well as Liverpool Outcome
Score to identify NDD over two years.
Expected findings and dissemination
We expect to find that OCT of the ONH can identify patients with severe brain swelling, and to
determine which ONH parameter(s) has the best sensitivity and specificity. The links between
retinal, cerebral ischaemia and neurological outcomes in CM are less well established, but the
study will determine whether OCT of the macula has predictive value for NDD.
The study findings and results will be shared in a timely manner with COMREC, UoL sponsor,
QECH Medical Director and Wellcome Trust. Results will be presented at Malawi, UK and
international scientific meetings, and by open-access publication (as required by the funder).
This will include the KUHeS Research Dissemination Day and MLW Annual Scientific
Meeting.
Description
Keywords
Outcome of cerebral malaria using optical coherence tomography