Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria

Nicole Fortier O'Brien, Tshimanga Mutatshi Taty, Melissa Moore-Clingenpeel, Joseph Bodi Mabiala, Jean Mbaka Pongo, Davin Ambitapio Musungufu, Mananu Uchama, Marcel Yotebieng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: To evaluate neurovascular changes in pediatric patients with cerebral malaria. Study design: African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. Results: In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%), microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76% had normal TCD findings (P <.001). Impaired autoregulation was present in 80% of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P =.014). Overall mortality was 24% (n = 39). Neurologic deficits were evident in 21% of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1) (P ≤.001). Conclusions: Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.

Original languageEnglish (US)
Pages (from-to)116-124.e3
JournalJournal of Pediatrics
Volume203
DOIs
StatePublished - Dec 2018
Externally publishedYes

Fingerprint

Cerebral Malaria
Doppler Transcranial Ultrasonography
Doppler Ultrasonography
Nervous System
Hyperemia
Homeostasis
Phenotype
Intracranial Vasospasm
Neurologic Manifestations
Survivors
Pediatrics
Mortality
Wounds and Injuries

Keywords

  • central nervous system infection
  • cerebral blood flow
  • global health
  • transcranial Doppler ultrasound
  • under five mortality

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

O'Brien, N. F., Mutatshi Taty, T., Moore-Clingenpeel, M., Bodi Mabiala, J., Mbaka Pongo, J., Ambitapio Musungufu, D., ... Yotebieng, M. (2018). Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria. Journal of Pediatrics, 203, 116-124.e3. https://doi.org/10.1016/j.jpeds.2018.07.075

Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria. / O'Brien, Nicole Fortier; Mutatshi Taty, Tshimanga; Moore-Clingenpeel, Melissa; Bodi Mabiala, Joseph; Mbaka Pongo, Jean; Ambitapio Musungufu, Davin; Uchama, Mananu; Yotebieng, Marcel.

In: Journal of Pediatrics, Vol. 203, 12.2018, p. 116-124.e3.

Research output: Contribution to journalArticle

O'Brien, NF, Mutatshi Taty, T, Moore-Clingenpeel, M, Bodi Mabiala, J, Mbaka Pongo, J, Ambitapio Musungufu, D, Uchama, M & Yotebieng, M 2018, 'Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria', Journal of Pediatrics, vol. 203, pp. 116-124.e3. https://doi.org/10.1016/j.jpeds.2018.07.075
O'Brien NF, Mutatshi Taty T, Moore-Clingenpeel M, Bodi Mabiala J, Mbaka Pongo J, Ambitapio Musungufu D et al. Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria. Journal of Pediatrics. 2018 Dec;203:116-124.e3. https://doi.org/10.1016/j.jpeds.2018.07.075
O'Brien, Nicole Fortier ; Mutatshi Taty, Tshimanga ; Moore-Clingenpeel, Melissa ; Bodi Mabiala, Joseph ; Mbaka Pongo, Jean ; Ambitapio Musungufu, Davin ; Uchama, Mananu ; Yotebieng, Marcel. / Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria. In: Journal of Pediatrics. 2018 ; Vol. 203. pp. 116-124.e3.
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abstract = "Objective: To evaluate neurovascular changes in pediatric patients with cerebral malaria. Study design: African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. Results: In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26{\%}), low flow in 46 (28{\%}), microvascular obstruction in 35 (22{\%}), cerebral vasospasm in 21 (13{\%}), and isolated posterior hyperemia in 7 (4{\%}). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76{\%} had normal TCD findings (P <.001). Impaired autoregulation was present in 80{\%} of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P =.014). Overall mortality was 24{\%} (n = 39). Neurologic deficits were evident in 21{\%} of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95{\%} CI 1.06-1.12) than in others (0.98, 95{\%} CI 0.95-1) (P ≤.001). Conclusions: Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.",
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AU - Bodi Mabiala, Joseph

AU - Mbaka Pongo, Jean

AU - Ambitapio Musungufu, Davin

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N2 - Objective: To evaluate neurovascular changes in pediatric patients with cerebral malaria. Study design: African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. Results: In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%), microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76% had normal TCD findings (P <.001). Impaired autoregulation was present in 80% of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P =.014). Overall mortality was 24% (n = 39). Neurologic deficits were evident in 21% of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1) (P ≤.001). Conclusions: Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.

AB - Objective: To evaluate neurovascular changes in pediatric patients with cerebral malaria. Study design: African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. Results: In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%), microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76% had normal TCD findings (P <.001). Impaired autoregulation was present in 80% of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P =.014). Overall mortality was 24% (n = 39). Neurologic deficits were evident in 21% of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1) (P ≤.001). Conclusions: Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.

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KW - under five mortality

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