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Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive

BACKGROUND: Cerebral 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 abnormali...

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Autores principales: O’Brien, Nicole F., Fonseca, Yudy, Johnson, Hunter C., Postels, Douglas, Birbeck, Gretchen L., Chimalizeni, Yamikani, Seydel, Karl B., Bernard Gushu, Montfort, Phiri, Tusekile, June, Sylvester, Chetcuti, Karen, Vidal, Lorenna, Goyal, Manu S., Taylor, Terrie E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210743/
https://www.ncbi.nlm.nih.gov/pubmed/35729574
http://dx.doi.org/10.1186/s12936-022-04163-0
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author O’Brien, Nicole F.
Fonseca, Yudy
Johnson, Hunter C.
Postels, Douglas
Birbeck, Gretchen L.
Chimalizeni, Yamikani
Seydel, Karl B.
Bernard Gushu, Montfort
Phiri, Tusekile
June, Sylvester
Chetcuti, Karen
Vidal, Lorenna
Goyal, Manu S.
Taylor, Terrie E.
author_facet O’Brien, Nicole F.
Fonseca, Yudy
Johnson, Hunter C.
Postels, Douglas
Birbeck, Gretchen L.
Chimalizeni, Yamikani
Seydel, Karl B.
Bernard Gushu, Montfort
Phiri, Tusekile
June, Sylvester
Chetcuti, Karen
Vidal, Lorenna
Goyal, Manu S.
Taylor, Terrie E.
author_sort O’Brien, Nicole F.
collection PubMed
description BACKGROUND: Cerebral 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. METHODS: This 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. RESULTS: One 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). CONCLUSIONS: Common 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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spelling pubmed-92107432022-06-22 Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive O’Brien, Nicole F. Fonseca, Yudy Johnson, Hunter C. Postels, Douglas Birbeck, Gretchen L. Chimalizeni, Yamikani Seydel, Karl B. Bernard Gushu, Montfort Phiri, Tusekile June, Sylvester Chetcuti, Karen Vidal, Lorenna Goyal, Manu S. Taylor, Terrie E. Malar J Research BACKGROUND: Cerebral 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. METHODS: This 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. RESULTS: One 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). CONCLUSIONS: Common 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. BioMed Central 2022-06-21 /pmc/articles/PMC9210743/ /pubmed/35729574 http://dx.doi.org/10.1186/s12936-022-04163-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
O’Brien, Nicole F.
Fonseca, Yudy
Johnson, Hunter C.
Postels, Douglas
Birbeck, Gretchen L.
Chimalizeni, Yamikani
Seydel, Karl B.
Bernard Gushu, Montfort
Phiri, Tusekile
June, Sylvester
Chetcuti, Karen
Vidal, Lorenna
Goyal, Manu S.
Taylor, Terrie E.
Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title_full Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title_fullStr Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title_full_unstemmed Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title_short Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
title_sort mechanisms of transcranial doppler ultrasound phenotypes in paediatric cerebral malaria remain elusive
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210743/
https://www.ncbi.nlm.nih.gov/pubmed/35729574
http://dx.doi.org/10.1186/s12936-022-04163-0
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