Observational studyMalaria journal2022
Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.
Observational study in Malaria journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Systematic Review of Commercially Available Clinical CMUT-Based Systems for Use in Medical Ultrasound Imaging: Products, Applications, and Performance.Sensors (Basel, Switzerland) · 2025Pooled it
- Noninvasive malaria detection beyond blood sampling.Sensors & diagnostics · 2026Review
- Clinical Applications of Point-of-Care and Diagnostic Transcranial Doppler in the Pediatric Acute Care Setting: A Scoping Review.Neurocritical care · 2026Article
- Advancing Understanding of Cerebrovascular Hemodynamic Perturbations in Pediatric Cerebral Malaria Using a Modified Critical Closing Pressure Evaluation- A Prospective, Observational Study.Neurocritical care · 2025Observational
- The brain shock index: repurposing the Lindegaard ratio for detecting cerebral hypoperfusion in children with cerebral malaria.The ultrasound journal · 2025Article
- Article
- Revising the Interpretation of Transcranial Doppler Ultrasound Examinations in Pediatric Cerebral Malaria.The American journal of tropical medicine and hygiene · 2024Article
- Variability of day-to-day pulsatility index change in children with cerebral malaria.Frontiers in neurology · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- Article
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundCerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes.
methodsThis was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score.
resultsOne hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05).
conclusionsCommon pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.
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