Predicting acute and post-recovery outcomes in cerebral malaria by Optical Coherence Tomography
| dc.contributor.author | Beare, Nicholas | |
| dc.date.accessioned | 2022-07-20T09:17:12Z | |
| dc.date.available | 2022-07-20T09:17:12Z | |
| dc.date.issued | 2022-06-02 | |
| dc.description.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 Formatted: Superscript 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. | en_US |
| dc.description.sponsorship | University of Liverpool | en_US |
| dc.identifier.uri | http://rscarchive.kuhes.ac.mw/handle/20.500.12988/1029 | |
| dc.language.iso | en | en_US |
| dc.publisher | Kamuzu University of Health Sciences | en_US |
| dc.relation.ispartofseries | Ethics Approval;P.11/21/3460 | |
| dc.subject | Outcome of cerebral malaria using optical coherence tomography | en_US |
| dc.title | Predicting acute and post-recovery outcomes in cerebral malaria by Optical Coherence Tomography | en_US |
| dc.type | Musical Score | en_US |