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Cerebral malaria is the most common complication and cause of death
in severe P. falciparum infection. In falciparum malaria, 10% of all admissions
and 80% of deaths are due to the C.N.S. involvement. On the other hand, C.N.S.
manifestations are fairly common in malaria and it could be due to not only severe
P. falciparum infection, but also high-grade fever and antimalarial drugs. Therefore, it is
extremely important to differentiate between these so as to avoid unnecessary anxiety and
improper treatment.
Manifestations
of cerebral dysfunction include any degree of impaired consciousness, delirium, abnormal
neurological signs, and focal and generalized convulsions. In severe P. falciparum
malaria, the neurological dysfunction can manifest suddenly following a generalized
seizure or gradually over a period of hours.
Causes of neurological manifestations in
malaria:
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High-grade fever alone can produce
impairment of consciousness, febrile convulsions (in children) and psychosis. These
manifestations subside with the decrease in the body temperature. Such cases and patients
with unimpaired consciousness after seizures tend to have good prognosis.
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Antimalarial drugs like chloroquine,
quinine, mefloquine and halofantrine also can cause altered behaviour, convulsions,
hallucinations and even psychosis. Absence of high-grade fever and of falciparum
parasitemia may suggest such a possibility.
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Hypoglycemia, either due to severe
malaria or due to drugs like quinine, may also present with similar manifestations.
Hypoglycemia is more common in pregnancy. It may be worthwhile considering this
possibility in ALL cases and to administer 25-50% dextrose intravenously.
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Hyponatremia, most often in the
elderly and caused by repeated vomiting, is another important cause for neurological
manifestations.
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Severe anaemia and hypoxemia can also
cause cerebral dysfunction, particularly in children.
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There could be other causes for
neurological dysfunction in patients with malaria like vascular disease, other
neurological infections and diseases. Focal neurological deficits, neck rigidity,
photophobia, papilloedema and neurological sequelae are very rare in falciparum malaria
and such a picture would therefore suggest these other possibilities.
A strict definition of cerebral malaria
has been recommended for sake of clarity and this requires the presence of unarousable
coma, exclusion of other encephalopathies and confirmation of P. falciparum
infection. However, all patients with P. falciparum malaria with neurological
manifestations of any degree should be treated as cases of cerebral malaria.
Pathophysiology: Cerebral malaria is
the most important complication of falciparum malaria. However, its pathophysiology is not
completely understood. The basic underlying defect seems to be clogging of the cerebral
micocirculation by the parasitized red cells. These cells develop knobs on their surface
and develop increased cytoadherent properties, as a result of which they tend to adhere to
the endothelium of capillaries and venules. This results in sequestration of the parasites
in these deeper blood vessels. Also, rosetting of the parasitized and non-parasitized red
cells and decreased deformability of the infected red cells further increases the clogging
of the microcirculation. It has been observed that the adhesiveness is greater with the
mature parasites. Obstruction to the cerebral microcirculation results in hypoxia and
increased lactate production due to anaerobic glycolysis. The parasitic glycolysis may
also contribute to lactate production. In patients with cerebral malaria, C.S.F. lactate
levels are high and significantly higher in fatal cases than in survivors. The adherent
erythrocytes may also interfere with gas and substrate exchange throughout the brain.
However, complete obstruction to blood flow is unlikely, since the survivors rarely have
any permanent neurological deficit.
Vascular permeability is found to be
mildly increased, however, no definite evidence of cerebral edema has been found on
imaging studies. 80% children with cerebral malaria have raised ICT, due to increased
cerebral blood volume and biomass rather than increased permeability. The mechanism of
coma is not clearly known. Increased cerebral anaerobic glycolysis, intereference with
neurotransmission by sequestered and highly metabolically active parasites have been
blamed. Cytokines induce nitric oxide synthesis in leukocytes, smooth muscle cells,
microglia and endothelium and NO is a potent inhibitor of neurotransmission.
See Pathology
Neurological signs in cerebral malaria:
As per the definition, patient should have
unarousable coma, not responding to noxious stimuli with a Glasgow coma scale of <7/15.
Mild neck stiffness may be seen, however, neck rigidity and photophobia and signs of
raised intracranial tension are absent. Retinal haemorrhages occur in about 15% of cases,
exudates are rare. Pupils are normal. Papilloedema is rare and should suggest other
possibilities. A variety of transient abnormalities of eye movements, especially
dysconjugate gaze, are observed. Fixed jaw closure and tooth grinding (bruxism) are
common. Pouting may occur or a pout reflex may be ellicitable, but other primitive reflexes
are usually absent. The corneal reflexes are preserved except in case of deep coma. Motor
abnormalities like decerebrate rigidity, decorticate rigidity and opisthotonus can occur.
Deep jerks and plantar reflexes are variable. Abdominal and cremasteric reflexes are not
ellicitable. These signs help in distinguishing from behavioural problems due to fever of
other causes.
These patients may also have anemia,
jaundice and hepatosplenomegaly.
Investigations: Lumbar puncture and
C.S.F. analysis may have to be done in all doubtful cases and to rule out associated
meningitis. In malaria, C.S.F. pressure is normal to elevated, fluid is clear and WBCs are
fewer than 10/µl; protein and lactic acid levels are elevated.
E.E.G. may show non-specific abnormalities.
C.T. scan of the brain is usually normal.
Cerebral malaria in
children
Management:
1. Nursing care: Meticulous nursing
is the most important aspect of management in these patients.
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Maintain a clear airway. In cases of
prolonged, deep coma, endotracheal intubation may be indicated.
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Turn the patient every two hours.
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Avoid soiled and wet beds.
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Nurse in semi-prone position with foot-end
elevation to prevent aspiration.
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Maintain strict intake/output record.
Observe for high coloured or black urine.
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Monitor vital signs every 4-6 hours.
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Changes in levels of sensorium, occurrence
of convulsions should also be observed.
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If the temperature is above 390 C,
tepid sponging and fanning must be done.
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Naso-gastric aspiration to prevent
aspiration pneumonia.
2. Urethral catheter can be inserted
for monitoring urine output.
3. Phenobarbitone injection, 10-15
mg/kg body weight should be given intramuscularly to prevent convulsions. And when
convulsions do occur, they can be treated with Diazepam by slow intravenous injection,
(0.15 mg/kg, maximum of 10 mg), or intrarectally (0.5-1.0 mg/kg).
4. Do not administer the following: Corticosteroids;
other anti inflammatory drugs; anti oedema drugs like mannitol, urea, invert sugar; low
molecular weight dextran; adrenaline; heparin; pentoxifylline; hyperbaric oxygen;
ciclosporin etc.
5. Antimalarial treatment: Parenteral
Quinine has been traditionally the treatment of choice for cerebral malaria. Artemisinin
derivatives have been proved to be equally, if not more, effective in treating cerebral
malaria. (For details see Treatment of P.
falciparum malaria)
Prognosis: Cerebral malaria carries
a mortality of around 20% in adults and 15% in children. Residual deficits are unusual in
adults (<3%). About 10% of the children (particularly those with recurrent
hypoglycemia, severe anemia, repeated seizures and deep coma), who survive cerebral
malaria may have persistent neurological deficits.
Cerebellar dysfunction: Rarely,
cases of falciparum malaria may present with cerebellar ataxia with unimpaired
consciousness. It may even occur 3-4 weeks after an attack of falciparum malaria. It
completely recovers over 1-2 weeks.
Malarial psychosis: Occasionally
patients with malaria may present with organic brain syndrome. More often it can develop
due to drugs like chloroquine and mefloquine. It can also develop during convalescence
after attacks of otherwise uncomplicated malaria. Malaria can also exacerbate pre-existing
psychiatric illness. Patients can manifest with depression, paranoia, delusions and
personality changes. Most of these are self-limiting and improve in a matter of days.
In a study of 118 cases of malaria in
Mangalore, Nagesh Pai, Satish Rao and B.S. Kakkilaya found varied psychiatric
manifestations. Most of these patients were already on antimalarial treatment at the time
of referral to the psychiatric service (unpublished data).
| Feature |
(n=118) |
Feature |
(n=118) |
| Delirium |
22 |
Organic
hallucinosis |
12 |
| Organic
catatonic disorder |
4 |
Organic
delusional disorder |
9 |
| Organic mania |
7 |
Organic
Depressive disorder |
13 |
| Organic anxiety |
26 |
Organic
dissociative disorder |
2 |
| Mild cognitive
disorder |
4 |
Multiple vague
complaints > 7days |
8 |
| Headache >7
days |
11 |
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