Cerebral Malaria This is a complication of severe falciparum malaria.

SEVERE MALARIA is defined as Acute complicated malaria from P.falciparum with one or more of the following life-threathening complications  Severe normocytic anaemia  Cerebral Malaria  Hypoglycaemia  Metabolic acidosis with respiratory distress  Fluid and electrolyte disturbances  Acute renal failure Hyperpyrexia Generalized convulsions

Hyperparasitaemia Jaundice Abnormal bleeding Circulatory collapse, shock, septicaemia (Algid malaria Haemoglbinuria Acute pulmonary oedema These manifestations can occur singly or in combination in the same patient

CEREBRAL MALARIA Cerebral malaria is defined as unrousable coma not attributable to any other cause in a patient with P. falciparum malaria. The strict definition of cerebral malaria requires the presence of P. falciparum parasitemia and persistence of coma for >30mins after a convulsion, and other causes (e.g. hypoglycemia, bacterial meningitis and viral encephalitis) ruled out.

PATHOGENESIS AND PATHOLOGY OF CEREBRAL MALARIA Pathology associated with all malarial species are related to the rupture of infected erythrocytes and the release of parasite material and metabolites, hemozoin (ie, malaria pigment) and cellular debris. There is sequestration of the infected erythrocytes in the cerebral microvasulature. Sequestration refers to the cytoadherence of trophozoite- and schizont-infected erythrocytes to endothelial cells of deep vascular beds in the brain.

Cerebral malaria is a common clinical presentation and cause of death in children with severe malaria. cerebral malaria usually occurred in children over 18 months of age.

Clinical features The earliest symptom of cerebral malaria in children is usually fever (37.5–41°C), followed by failure to eat or drink. Vomiting and cough are common; diarrhoea is unusual. The history of symptoms preceding coma may be very brief – commonly one or two days. Therefore onset may be dramatic with a generalized convulsion, or gradual with initial drowsiness and confusion, followed by coma lasting from several hours to several days.

Coma is unarousable (Blantyre coma score of <2) and often deepening. The deeper the coma, the worse is the prognosis. Convulsions are common before or after the onset of coma. Can be focal or generalized. Occur in about 80% of subjects. They are significantly associated with morbidity and sequelae.

They may present in a very subtle way, important signs include: intermittent nystagmus, salivation, minor twitching of a single digit or a corner of the mouth and an irregular breathing pattern. However convulsions are generalized in most cases with nonspecific abnormalities on electroencephalographic examination. With prompt and effective treatment, there is resolution of coma within 1-2 days

In children, convulsions due to malaria must be differentiated from febrile convulsions. In the latter, coma usually does not last for more than half an hour, although some children do not regain full consciousness until 30–60 minutes after the ictal phase. A child who loses consciousness after a febrile convulsion should not be classified as having cerebral malaria unless coma persists for more than 1 hour after the convulsion. This also distinguishes cerebral malaria from transient postictal sleep.

On examination, neurologic abnormalities resemble those of a diffuse symmetrical, upper motor neurone dysfunction Nuchal rigidity and focal neurologic signs are rare. Corneal and pupillary reflexes are usually intact. Brain stem disturbances such as disconjugate gaze and decerebrate and decorticate postures may be present

In some children, extreme opisthotonus is seen which may lead to a mistaken diagnosis of meningitis The plantar responses are extensor in about half of the patients. Delirium, agitation, and even transient paranoid psychosis may develop as the patient recovers consciousness.

Other neurological signs include cranial nerve abnormalities, extrapyramidal tremor, and ataxia. In children with profound coma, corneal reflexes and “doll’s eye” movements may be abnormal. Abnormal posturing, absence of corneal reflex and depth and duration of coma are indicators of poor prognosis.

The child with cerebral malaria may also have anaemia, respiratory distress (acidosis) and hypoglycaemia. Anaemia can range in the degree of mild to severe in cerebral malaria Hyperparasitaemia (>=20% of circulating infected RBCs) may be present.

MANAGEMENT Lumbar puncture is mandatory. CSF opening pressure is usually raised. Leukocytosis is not unusual in severe disease and does not necessarily imply an associated bacterial infection. careful nursing and monitoring of the unconscious patient. Monitor the Haemoglobin treat the anaemia if severe (Hb <5gm%). Transfuse patient with 10mls/kg of pack cells or 15mls/kg of sedimented cells. Monitor pt. for hypoglycaemia

If hypoglycaemia occurs, give intravenous 50% dextrose in a dose of 2.0 ml/kg of body weight (1 g/kg) diluted in approximately the same volume of IV fluid slowly over several minutes. If 10% dextrose is available, give appropriately more to provide the same amount of dextrose (1.0 g/kg). This should be followed by a slow intravenous infusion of 5% or 10% dextrose to prevent recurrence of hypoglycaemia. Monitoring of blood glucose levels should continue even after successful correction as hypoglycaemia may recur.

ANTIMALARIAL TREATMENT Ideally, antimalarial drugs should be given initially by intravenous infusion; this should be replaced by oral administration as soon as possible. Quinine is the drug of choice. 10mg/kg/dose I/V in 10ml/kg of 5% dextrose given over 2-4hours 8hrly in 24 hours. This dose should be repeated every 8 hours, calculated from the beginning of the previous infusion, until the patient can swallow, then quinine tablets, 10 mg salt/kg, 8-hourly to complete a 7-day course of treatment Artemether can be administered intramuscularly.

Convulsions Treat convulsions with intravenous diazepam, 0.3 mg/kg of body weight as a slow bolus (“push”) over 2 minutes or 0.5mg/kg of body weight intrarectally. Alternatively, paraldehyde 0.1 ml/kg of body weight may be given by deep intramuscular injection using a sterile glass syringe. If seizure persists, try other anticonvulsants

COMPLICATION About 10% of children who survive cerebral malaria have neurological sequelae which persist into the convalescent period. Sequelae may take the form of cerebellar ataxia, hemiparesis, speech disorders, cortical blindness, behavioural disturbances, motor disorders (dyskinesia, hemiplegia, and ataxia) with hypotonia or generalized spasticity. 70% to 80% of these deficits resolve during the following 6 months.

The fatality rate for patients with strictly defined cerebral malaria varies by facility and geographic area. Rates from 4% to 46% have been reported