This document discusses cerebral malaria, beginning with its definition as an unarousable coma caused by Plasmodium falciparum infection. It then covers the disease's epidemiology, noting it causes 300-500 million cases and over 1 million deaths annually worldwide, especially in Africa. The pathophysiology section explores the mechanical hypothesis of sequestration and rosetting of infected red blood cells in the brain vasculature and the toxin/cytokine hypothesis of an inflammatory response. Clinical features include seizures, altered consciousness, and possible neurological deficits upon recovery. Diagnosis relies on blood smears identifying the parasite, and treatment involves intensive care, antimalarial drugs like artesunate, and supportive care.

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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