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Cerebrospinal Fluid Studies in Kenyan Children with Severe Falciparum Malaria
N Mturi1, G Keir, C A Maclennan
1Kenya Medical Research Institute, Centre for Geographic Medicine Research (Coast), P. O. Box 230, Kilifi, Kenya.
Insights
Neurological complications in severe malaria may stem from a mildly impaired blood-brain barrier (BBB) and elevated excitotoxic amino acids like aspartate. Further research is needed to confirm immunoglobulin synthesis in the brain.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pathology
Background:
- The exact causes of neurological complications in severe Plasmodium falciparum malaria remain poorly understood.
- Investigating the blood-brain barrier (BBB) integrity and markers of brain damage is crucial for understanding malaria's neurological impact.
Purpose of the Study:
- To assess blood-brain barrier (BBB) integrity in children with severe falciparum malaria.
- To identify evidence of intrathecal synthesis of immunoglobulins and excitotoxins.
- To explore the contribution of these factors to neurological complications.
Main Methods:
- Paired plasma and cerebrospinal fluid (CSF) samples were collected from children with severe falciparum malaria.
- Proteins (albumin, immunoglobulins) and amino acids (aspartate) were measured in CSF and plasma.
- Blood-brain barrier (BBB) integrity was assessed using the CSF to plasma albumin ratio (Q(alb)).
Main Results:
- Mild blood-brain barrier (BBB) impairment was observed in 51% of children, extending beyond cerebral malaria.
- Elevated CSF concentrations of aspartate and other amino acids were found, suggesting potential excitotoxicity.
- Evidence of intrathecal immunoglobulin synthesis (IgM and IgG) was detected in a significant proportion of patients.
Conclusions:
- Mild blood-brain barrier (BBB) impairment occurs in severe malaria, affecting children with cerebral, prostrate, and seizure presentations.
- Intrathecal synthesis of immunoglobulins is suggested and warrants further investigation.
- Elevated aspartate levels and potential immunoglobulin synthesis may contribute to the pathogenesis of neurological complications in malaria.
Abstract:
The pathogenesis of the neurological complications of Plasmodium falciparum malaria is unclear. We measured proteins and amino acids in paired plasma and cerebrospinal fluid (CSF) samples in children with severe falciparum malaria, to assess the integrity of the blood brain barrier (BBB), and look for evidence of intrathecal synthesis of immunoglobulins, excitotoxins and brain damage. METHODS: Proteins of different molecular sizes and immunoglobulins were measured in paired CSF and plasma samples in children with falciparum malaria and either impaired consciousness, prostrate, or seizures. RESULTS: The ratio of CSF to plasma albumin (Q(alb)) exceeded the reference values in 42 (51%) children. The CSF concentrations of the excitotoxic amino acid aspartate and many non-polar amino acids, except alanine, were above the reference value, despite normal plasma concentrations. IgM concentrations were elevated in 21 (46%) and the IgM index was raised in 22 (52%). Identical IgG oligoclonal bands were found in 9 (35%), but only one patient had an increase in the CSF IgG without a concomitant increase in plasma indicating intrathecal synthesis of IgG. CONCLUSIONS: This study indicates that the BBB is mildly impaired in some children with severe falciparum malaria, and this impairment is not confined to cerebral malaria, but also occurs in children with prostrate malaria and to a lesser extent the children with malaria and seizures. There is evidence of intrathecal synthesis of immunoglobulins in children with malaria, but this requires further investigation. This finding, together with raised level of excitotoxic amino acid aspartate could contribute to the pathogenesis of neurological complications in malaria.
