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

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.

Cerebral Blood Flow Velocity is Not Associated with Serum Hemoglobin in Children with Malaria-Associated Anemia.

BACKGROUND AND PURPOSE: Hemoglobin (Hbg) is often thought to impact cerebral blood flow velocity (CBFV). This study was performed to investigate the relationship between Hbg value and CBFV in African children with malaria. METHODS: In this prospective, observational study, children aged 3 months to 18 years with malaria and a normal Blantyre coma score underwent a single transcranial Doppler ultrasound (TCD) examination with a concurrent Hbg check. RESULTS: One hundred fifty-six children with a mean age of 43 months were enrolled. Thirty-three children (21%) had severe anemia (Hbg <5g/dL), 46 (29%) had moderate anemia (Hbg 5-6.9 g/dL), 63 children (41%) had mild anemia (7-9.9 g/dL), and 14 children (9%) had no anemia (Hbg >10 g/dL) at the time of TCD examination. Mean averaged CBFV in the middle cerebral artery (MCA) for the cohort was 99% of predicted based on normative values standardized for age. There was no significant correlation between Hbg levels and measured CBFV in the MCA (r = -.09; 95% CI, -.24-.07; P = .29). CONCLUSION: In a large sample of African children with malaria, Hbg did not correlate with CBFVs as measured by TCD. Future work that includes baseline TCD measurements and Hbg values as well as other physiological parameters known to influence CBFVs is necessary to confirm these findings.

Transcranial Doppler Ultrasonographic Evaluation of Cerebrovascular Abnormalities in Children With Acute Bacterial Meningitis.

Introduction: Bacterial meningitis (BM) is a global public health concern that results in significant morbidity and mortality. Cerebral arterial narrowing contributes to stroke in BM and may be amenable to intervention. However, it is difficult to diagnose in resource-limited settings where the disease is common. Methods: This was a prospective observational study from September 2015 to December 2019 in sub-Saharan Africa. Children 1 month-18 years of age with neutrophilic pleocytosis or a bacterial pathogen identified in the cerebrospinal fluid were enrolled. Transcranial Doppler ultrasound (TCD) of the middle cerebral arteries was performed daily with the aim to identify flow abnormalities consistent with vascular narrowing. Results: Forty-seven patients were analyzed. The majority had Streptococcus pneumoniae (36%) or Neisseria meningitides (36%) meningitis. Admission TCD was normal in 10 (21%). High flow with a normal pulsatility index (PI) was seen in 20 (43%) and high flow with a low PI was identified in 7 (15%). Ten (21%) had low flow. All children with a normal TCD had a good outcome. Patients with a high-risk TCD flow pattern (high flow/low PI or low flow) were more likely to have a poor outcome (82 vs. 38%, p = 0.001). Conclusions: Abnormal TCD flow patterns were common in children with BM and identified those at high risk of poor neurological outcome.