Is cerebrospinal fluid (CSF) pleocytosis typically absent in cerebral malaria?

Cerebrospinal Fluid Pleocytosis in Cerebral Malaria

CSF pleocytosis is typically absent in cerebral malaria, and its presence should prompt consideration of alternative or concurrent diagnoses. 1

Diagnostic Findings in Cerebral Malaria

• The absence of CSF pleocytosis is a characteristic feature of cerebral malaria, with normal CSF cell counts observed in the vast majority of cases 2
• When evaluating patients with suspected cerebral malaria, CSF analysis typically shows:
  • Normal white blood cell counts (absence of pleocytosis) 2, 3
  • Normal CSF opening pressures in approximately 79% of cases 2
  • Lower CSF opening pressures in fatal cases compared to survivors 2
  • Altered biochemistry including lower glucose levels and higher protein levels compared to controls 3

Differential Diagnosis When CSF Pleocytosis is Present

• The presence of CSF pleocytosis in a patient with suspected cerebral malaria should trigger consideration of:
  • Alternative diagnoses such as viral encephalitis, which typically presents with CSF pleocytosis 1, 3
  • Concurrent infections, as co-infection with bacterial meningitis or viral encephalitis can occur 1, 4
  • Other tropical diseases that can cause meningitis with pleocytosis, such as angiostrongyliasis, gnathostomiasis, and schistosomiasis 1

Diagnostic Approach

• When evaluating patients returning from malaria-endemic areas with neurological symptoms:
  • Perform rapid blood malaria antigen tests and examine three thick and thin blood films for malaria parasites, regardless of CSF findings 1
  • Look for other clues to malaria such as thrombocytopenia or malaria pigment in neutrophils and monocytes 1
  • CSF analysis should be performed to rule out other causes of encephalopathy 5
  • The CSF/serum adenosine deaminase (ADA) ratio and CSF glucose levels can help discriminate cerebral malaria from viral encephalitis 3

Management Implications

• If cerebral malaria is suspected despite the presence of CSF pleocytosis:
  • Do not delay antimalarial treatment while awaiting CSF analysis results, as prompt treatment is essential for reducing mortality 1
  • Intravenous artesunate is the first-line treatment for cerebral malaria 1
  • Consider empiric coverage for bacterial meningitis until cultures return negative, as co-infection is possible 1, 4

Clinical Pearls and Pitfalls

• The blood-CSF barrier remains essentially intact in patients with cerebral malaria, which explains the absence of pleocytosis 2
• Meningitis in the absence of pleocytosis is rare but can occur, particularly with bacterial infections 4
• In cases where both malaria parasitemia and CSF pleocytosis are present, consider the possibility of two concurrent infections rather than attributing all symptoms to cerebral malaria 1, 6
• CSF biomarkers such as IL-1ra, IL-8, IP-10, and others may be elevated in cerebral malaria despite the absence of pleocytosis, and could potentially serve as prognostic indicators 7