1. Cerebral malaria
By
Dr Ranganath Koggnur S
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2. Objectives
• Definition
• Epidemiology
• Pathophysiology
• Clinical features
• Investigations
• Treatment
• Conclusion
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3. Definition
• Manifestation of severe plasmodium falciparum malaria
• Unarousable coma more than 30 mts with a glasgow coma scale <7/15
with evidence of acute falciparum infection(asexual form in peripheral
blood smear)
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4. Epidemiology
WORLD
300 – 500 million cases ( 90% in Africa)
1.1 - 2.7 million deaths annually
INDIA
2.5 – 3 million cases / yr
1000 deaths / yr ( under estimate )
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5. PATHOGENESIS OF
CEREBRAL MALARIA
1. MECHANICAL HYPOTHESIS
Sequestration of RBC in the brain by
cytoadherence / Rosetting
2. Toxin/cytokine HYPOTHESIS
Malarial toxin induced cytokines
stimulating excessive Nitric oxide
Production.
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6. MECHANICAL HYPOTHESIS
• Cytoadherence
parasite after invading RBC membrane, 12/15 hrs later protruberances
appear on the erythrocyte’s surface. These “knobs” extrude a high
molecular weight, antigenically variant, strain specific erythrocyte
membrane adhesive protien (pfEMP1) that mediates attachement to
receptors on venular and capillary endothelium. Thus eventually block
capillaries and venules.
• Rosetting
Binding of 2 or more uninfected RBC’s to an infected RBCs.
• Agglutination
The binding of 2/more infected RBC’s.
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7. Toxin/cytokine HYPOTHESIS
• Glycolipid material released on merozite rupture initiates cytokine
cascade from macrophages and monocyte series and endothelium with
release of interleukin-1, TNF alpha, interleukin-6 and interleukin-8.
• Evidence of positive correlation cytokine levels and prognosis.
• TNF alpha>100pg/ml is associated with cerebral pathology and death.
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8. HUMORAL HYPOTHESIS
MALARIAL TOXIN MACROPHAGE ACTIVATION
TNF alpha & IL – 6
↓
UNCONTROLLED NITRIC OXIDE
PRODUCTION
↓
Nitric Oxide diffuse blood brain barrier
IMPAIRS SYNAPTIC TRANSMISSION
( like general anaesthetics / ethanol )
↓
COMA
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9. • CEREBRAL MALARIA MECHANICAL HYPOTHESIS CAN NOT EXPLAIN
RELATIVE ABSENCE OF NEUROLOGICAL DEFICIT EVEN AFTER DAYS OF
COMA.
• TOXIN/CYTOKINE HYPOTHESIS CAN EXPLAIN THE RAPID RECOVERY OF
COMA AND ABSENCE OF NEUROLOGICAL DEFICIT.
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10. CLINICAL FEATURES
Onset
Acute – following seizures
Gradual
Consciousness
Drowsiness, confusion, disorientation, delirium and agitation.
Seizures
Repeated genaralised convulsions > 2/24 hrs.
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11. OTHER CLINICAL FEATURES
• Mild neck stiffness – no rigidity
• Papilloedema in < 1%
• Retinal hemorrhages – 15 %
• Pupils and corneal reflex – normal
• Transient dysconjugate gaze- no paresis
• Jaw jerk may be brisk
• Forced jaw closure/ Bruxism
• Motor system
- Decorticate rigidity
- Decerebrate rigidity
- opisthotonus
-Tone may be increased, decreased or normal
-Cremasteric and Abdominal reflex normal
-DTR and Plantar reflex variable
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12. OTHER CAUSES OF NEUROLOGICAL
DYSFUNCTION
Very high fever – febrile seizures, altered consciousness,Psychosis.
Antimalarial drugs – chloroquine, mefloquine.
HYPOGLYCEMIA – severe parasitemia,quinine.
Hyponatremia – vomiting, elderly patients.
Severe anemia
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13. Decerebrate and Decorticate rigidity
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14. Assymetric gaze and opisthotonus
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15. SEQUELE AND POST MALARIAL NEUROLOGICAL
SYNDROMES
3% in adults, 10% in children.
50% recover completely
25% partial recovery
25% no recovery
• Hemiparesis, hemisensory deficits, cotical blindness,
• cranial nerve palsies,(isolated 6th nerve palsy) ,foot drop,
• Extra pyramidal symptoms(chorea,athetosis,tremors)
• Sudden blindeness due to vitreous haemorrhage.
• Cerebellar ataxia
Acute febrile stage - with complete recovery, Delayed onset - 3-4 wks after
malaria
recovers by 3- 16 wks
• Psychiatric disturbances –
Depression, Amnesia, psychosis, personality changes, Delusion and
Hallucinations.
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16. Investigaions
Microscopic examination of blood film is gold standard for diagnosis of
malaria.
•Thick blood film
– Species specific and inexpensive.
•Thin blood film
– Rapid, species specific and inexpensive.
•PfHRP2 dipstick card test
– Rapid and sensitive, Detects only p falciparum.
•Role of PCR
– most sensitive and specific
– Results only after 24hrs
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17. Microscopy
• Thin blood film • Thick blood film
Schizonts Trophozoite Gamatocytes Schizonts
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18. Treatment
• Medical emergency Requires ICU care.
• Ventilatory support, cardiac monitoring.
• Correction of fluids, electrolytes and acid base balance.
• Blood transfusion(where facilities are available)
• Specific treatment
– Artesunate is drug of choice - 2.4mg/kg(2vails) iv at 0hr and 24hrs
then daily till pt can take orally.
– Quinine in case of first trimester of pregnanacy – 20mg/kg in
5%dextrose saline in 4hrs then 8th hrly orally to complete 7 days
– Doxycycline 3.5mg/kg/day for 7 days
– Tetracycline/clindamycin(children and pregnancy)
• ACT- COMBINATION THERAPY
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19. CONCLUSION
• Changing profile of clinical features of plasmodium
falciparum – cerebral malaria jaundice / renal failure/
MODS.
• Cytoadherence, rosetting, Nitric oxide and biomass
of brain are important pathogenic mechanisms in cerebral
malaria.
• Quinine & doxy / Artesunate & doxy are effective
combinations in treating cerebral malaria.
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