TY - JOUR
T1 - Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria
AU - O'Brien, Nicole Fortier
AU - Mutatshi Taty, Tshimanga
AU - Moore-Clingenpeel, Melissa
AU - Bodi Mabiala, Joseph
AU - Mbaka Pongo, Jean
AU - Ambitapio Musungufu, Davin
AU - Uchama, Mananu
AU - Yotebieng, Marcel
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/12
Y1 - 2018/12
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.
KW - central nervous system infection
KW - cerebral blood flow
KW - global health
KW - transcranial Doppler ultrasound
KW - under five mortality
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U2 - 10.1016/j.jpeds.2018.07.075
DO - 10.1016/j.jpeds.2018.07.075
M3 - Article
C2 - 30224088
AN - SCOPUS:85053214839
SN - 0022-3476
VL - 203
SP - 116-124.e3
JO - Journal of Pediatrics
JF - Journal of Pediatrics
ER -