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Representative images of Transcranial Doppler Ultrasound phenotypes in children with cerebral malaria. A Normal middle cerebral artery (MCA) TCD flow velocities and waveform for a 3-year-old child. B TCD with increased systolic flow velocity, increased diastolic flow velocity, Lindegaard ratio (LR) < 3. These findings represent a child categorized as having hyperaemia. C TCD with decreased systolic flow velocity, decreased diastolic flow velocity, decreased mean flow velocity. These findings represent a child categorized as having low flow. D TCD with normal systolic flow velocity, reduced diastolic flow velocity, increased pulsatility index. These findings represent a child categorized as having microvascular obstruction. E TCD with increased systolic flow velocity, increased diastolic flow velocity, LR > 3. These findings represent a child categorized as having cerebral vasospasm. F TCD with increased systolic flow velocity, increased diastolic flow velocity, increased mean flow velocity in the basilar artery. At the same time, all measurements in the MCAs were normal. These findings represent a child categorized as having isolated posterior circulation high flow
Source publication
Abstract 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,...
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The thigh-cuff release (TCR) maneuver is a physiological challenge that is widely used to assess dynamic cerebral autoregulation (dCA). It is often applied in conjunction with Transcranial Doppler ultrasound (TCD), which provides temporal information of the global flow response in the brain. This established method can only yield very limited insig...
Background
Changes in the direct current (DC) electroencephalography (EEG), so-called DC shifts, are observed during hypoxia, hypo-/hypercapnia, anesthetic administration, epileptic seizures, and spreading depolarizations. They are associated with altered cerebral ion currents across cell membranes and/or the blood–brain barrier (BBB). Here, we mea...
Citations
... Furthermore, as a result of its favorable attributes and the lack of alternate, available neuroimaging techniques, TCD is increasingly being used in the management of African children with sickle cell disease, obstructive hydrocephalus, sinus venous thrombosis, meningitis and cerebral malaria [5][6][7][8][9][10]. The interpretation of TCD examinations in this context is particularly problematic given the complete absence of normative data in African children. ...
Background and purpose:
Transcranial doppler ultrasound (TCD) is a tool that diagnoses and monitors pathophysiological changes to the cerebrovasculature. As cerebral blood flow velocities (CBFVs) increase throughout childhood, interpretation of TCD examinations in pediatrics requires comparison to age matched normative data. Large cohorts of healthy children have not been examined to develop these reference values in any population. There is a complete absence of normative values in African children where, due to lack of alternate neuroimaging techniques, utilization of TCD is rapidly emerging.
Materials and methods:
A prospective study of 710 healthy African children 3 months-15 years was performed. Demographics, vital signs, and hemoglobin values were recorded. Participants underwent a complete, non-imaging TCD examination. Systolic (Vs), diastolic (Vd), and mean (Vm) flow velocities and pulsatility index (PI) were calculated by the instrument for each measurement.
Results:
Vs, Vd, and Vm increased through early childhood in all vessels, with the highest CBFVs identified in children 5-5.9 years. There were few significant gender differences in CBFVs in any vessels in any age group. No correlations between blood pressure or hemoglobin and CBFVs were identified. Children in the youngest age groups had CBFVs similar to those previously published, whereas nearly every vessel in children ≥3 years had significantly lower Vs, Vd, and Vm.
Conclusions:
For the first time, reference TCD values for African children are established. Utilization of these CBFVs in the interpretation of TCD examinations in this population will improve the overall accuracy of TCD as a clinical tool on the continent.
Cerebral malaria (CM) is a severe neurological complication caused by Plasmodium falciparum parasites; it is characterized by the sequestration of infected red blood cells within the cerebral microvasculature. New findings, combined with a better understanding of the central nervous system (CNS) barriers, have provided greater insight into the players and events involved in CM, including site-specific T cell responses in the human brain. Here, we review the updated roles of innate and adaptive immune responses in CM, with a focus on the role of the perivascular macrophage–endothelium unit in antigen presentation, in the vascular and perivascular compartments. We suggest that these events may be pivotal in the development of CM.
Brain swelling is associated with death from cerebral malaria, but it is unclear whether brain swelling is caused by cerebral edema or vascular congestion—two pathological conditions with distinct effects on tissue hemoglobin concentrations. We used near-infrared spectroscopy (NIRS) to noninvasively study cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria. Cerebral malaria was defined by the presence of the malaria parasite Plasmodium falciparum on a blood smear, a Blantyre coma score of 2 or less, and retinopathy. Children with uncomplicated malaria ( n = 33) and healthy children ( n = 29) were enrolled as comparators. Cerebral microvascular hemoglobin concentrations were higher among children with cerebral malaria compared with those with uncomplicated malaria [median (25th, 75th): 145.2 (95.2, 190.0) μM versus 82.9 (65.7, 105.4) μM, P = 0.008]. Cerebral microvascular hemoglobin concentrations correlated with brain swelling score determined by MRI ( r = 0.37, P = 0.03). Fluctuations in cerebral microvascular hemoglobin concentrations over a 30-min time period were characterized using detrended fluctuation analysis (DFA). DFA determined self-similarity of the cerebral microvascular hemoglobin concentration signal to be lower among children with cerebral malaria compared with those with uncomplicated malaria [0.63 (0.54, 0.70) versus 0.91 (0.82, 0.94), P < 0.0001]. The lower self-similarity of the hemoglobin concentration signal in children with cerebral malaria suggested impaired regulation of cerebral blood flow. The elevated cerebral tissue hemoglobin concentration and its correlation with brain swelling suggested that excess blood volume, potentially due to vascular congestion, may contribute to brain swelling in cerebral malaria.
