Correspondence

Subarachnoid Hemorrhage in a Patient with Cerebral Malaria

N Engl J Med 1999; 341:611-613August 19, 1999

Article

To the Editor:

Cerebral malaria is seen mainly in children and nonimmune patients in African countries where infection with Plasmodium falciparum is endemic. Common symptoms are epileptic seizures, confusion, agitation, disorientation, and coma. Subarachnoid hemorrhage due to plasmodium infection is very rare,1 but its incidence may be underestimated. We describe a patient with cerebral malaria who presented with a subarachnoid hemorrhage.

Five days after returning from a trip to Kenya, a 54-year-old woman became progressively confused. Because she had multiple allergies, she had not received antimalarial medication prophylactically. On examination in the emergency room, she was obtunded and afebrile and had no focal neurologic signs. Computed tomographic scans of the brain revealed an extensive subarachnoid hemorrhage, with symmetric filling of the basal cisterns, a right frontal intraparenchymal hemorrhage, and blood in the right lateral ventricle (Figure 1AFigure 1Results of Cerebral Imaging, Laboratory Findings, and Clinical Course of the Patient.). This constellation typically reflects the rupture of an aneurysm of the anterior part of the circle of Willis. Nevertheless, cerebral angiography revealed no vascular abnormality. An intraventricular catheter was inserted to drain cerebrospinal fluid. The hematocrit was 0.39, and the white-cell count was 6700 per cubic millimeter. There was severe thrombocytopenia (platelet count, 13,000 per cubic millimeter). Blood screening revealed P. falciparum in 15 percent of erythrocytes. The serum creatinine concentration was normal.

Parasites were detected in specimens of blood (Figure 1B) and cerebrospinal fluid (Figure 1C). Treatment was started with intravenous quinine and doxycycline. Abdominal ultrasonography showed no splenomegaly. The parasite density peaked at 34 percent of erythrocytes. Concentrations of tumor necrosis factor α (TNF-α) in cerebrospinal fluid and serum were elevated. As the patient recovered, the concentration of TNF-α in cerebrospinal fluid and serum decreased (Figure 1D). On follow-up examination three months after the subarachnoid hemorrhage, the patient had mild impairment of her memory and selective attention.

The neuropathological hallmark of cerebral malaria is the sequestration of erythrocytes containing parasites in cerebral capillaries and venules. Infection with P. falciparum leads to an increase in serum TNF-α, whose concentrations correlate well with the severity of disease.3 By up-regulating endothelial adhesion molecules, TNF-α may promote cerebral sequestration of platelets and red cells.4 In our patient, changes in serum and cerebrospinal fluid TNF-α concentrations paralleled the course of neurologic symptoms. The subarachnoid hemorrhage in our patient may have been caused by the rupture of a small vessel plugged by red cells in combination with severe thrombocytopenia.

Claudius Gall, M.D.
Ludwig Maximilians University, D-81377 Munich, Germany

Andreas Spuler, M.D.
Klinikum Buch, D-13122 Berlin, Germany

Peter Fraunberger, M.D.
Ludwig Maximilians University, D-81377 Munich, Germany

4 References

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Citing Articles (3)

Citing Articles

1. 1

   Wael Radwan, Raja Sawaya. (2011) Intracranial haemorrhage associated with cerebral infections: A review. Scandinavian Journal of Infectious Diseases1-8
   CrossRef

2. 2

   Pedro Cabrales, Graziela M. Zanini, Diana Meays, John A. Frangos, Leonardo J.M. Carvalho. (2010) Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine. The American Journal of Pathology 176:3, 1306-1315
   CrossRef

3. 3

   Christopher Alan Moxon, Robert Simon Heyderman, Samuel Crocodile Wassmer. (2009) Dysregulation of coagulation in cerebral malaria. Molecular and Biochemical Parasitology 166:2, 99-108
   CrossRef