Malaria is caused by the protozoal parasite Plasmodium, transmitted to humans via the Anopheles mosquito. The disease is endemic to large parts of Africa, South America, and Southeast Asia.144 Cerebral malaria is an encephalopathy occurring in approximately 2% of outpatients and 10% of inpatients infected with Plasmodium falciparum. (P. malariae and P. vivax are infrequent causes of CNS malaria.)145

Clinical features of cerebral malaria

The World Health Organization definition of cerebral malaria requires:145

  1. unarousable coma
  2. evidence of acute infection with P. falciparum
  3. no other identifiable cause of coma

Clinical manifestations of cerebral malaria are diverse. Fever is nearly universal, as is comorbidity with clinical features of P. falciparum systemic infection. Clinicians working in tropical and subtropical regions regard any new CNS-attributable sign developing within the context of P. falciparum parasitemia as evidence of possible cerebral malaria.144

The cardinal feature is disturbed level of consciousness, usually ranging from lethargy to stupor to coma, although an agitated delirium can also occur. To conform to the strict diagnosis of cerebral malaria, the patient must remain comatose for more than 6 hours after seizure to distinguish the coma from postictal consciousness suppression.

Generalized tonic-clonic seizures occur in more than 40% of adult patients. Partial seizures are uncommon.13 Seizures are associated with prolonged coma and increased risk of neurologic sequelae and death.13,144

Possible seizure causes include:

  • cerebral hypoxia associated with cerebral malaria
  • fever
  • hypoglycemia
  • lactic acidosis
  • drugs (including antimalarials such as chloroquine and mefloquine)
  • other metabolic disturbances secondary to malarial systemic effects13,144

In children, cerebral malaria tends to progress more rapidly, and convulsions are a common early feature. In Malawi, for example, 82% of childhood cases had a history of convulsions, and almost one-fourth of these had seizures within 3 hours of admission.146

A variety of EEG abnormalities have been described. Because subclinical seizure activity is frequent, a low threshold for initiating EEG monitoring should be maintained.13,144

Neurologic sequelae of cerebral malaria, including epilepsy, affect approximately 10% of survivors; for unclear reasons, children tend to be more frequently affected than adults.146,147


Demonstration of parasitemia and species confirmation is by blood smear. The CSF profile in cerebral malaria is notable for occasional lymphocytic pleocytosis. The protein concentration may be slightly elevated, but glucose is usually normal.


Cerebral malaria is a medical emergency. Treatment is tripartite:

  • specific antimalarial therapy (via quinine, quinidine, etc.)
  • management of coexistent malarial complications including seizures
  • treatment of associated superinfections.144

At least initial management should be in an intensive care unit. Generalized seizures can be followed by rapid neurologic deterioration, so prompt treatment is required. Subclinical or nonconvulsive seizures should be suspected in patients with persistent coma.

Convulsions can be prevented by controlling fever and through judicious use of prophylactic anticonvulsants.13,144

Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133. 
With permission from Elsevier (

Reviewed By: 
Sunday, February 29, 2004