Cerebral malaria                      By             Dr Ranganath Koggnur S11/25/2010          Cerebral malaria   1
Objectives      •      Definition      •      Epidemiology      •      Pathophysiology      •      Clinical features      ...
Definition• Manifestation of severe plasmodium falciparum malaria• Unarousable coma more than 30 mts with a glasgow coma s...
EpidemiologyWORLD    300 – 500 million cases ( 90% in Africa)    1.1 - 2.7 million deaths annuallyINDIA    2.5 – 3 million...
PATHOGENESIS OF                     CEREBRAL MALARIA1. MECHANICAL HYPOTHESIS    Sequestration of RBC in the brain by    cy...
MECHANICAL HYPOTHESIS•   Cytoadherence    parasite after invading RBC membrane, 12/15 hrs later protruberances    appear o...
Toxin/cytokine HYPOTHESIS•   Glycolipid material released on merozite rupture initiates cytokine    cascade from macrophag...
HUMORAL HYPOTHESIS             MALARIAL TOXIN MACROPHAGE ACTIVATION                          TNF alpha & IL – 6           ...
•   CEREBRAL MALARIA MECHANICAL HYPOTHESIS CAN NOT EXPLAIN    RELATIVE ABSENCE OF NEUROLOGICAL DEFICIT EVEN AFTER DAYS OF ...
CLINICAL FEATURESOnset   Acute – following seizures   GradualConsciousness   Drowsiness, confusion, disorientation, deliri...
OTHER CLINICAL FEATURES•   Mild neck stiffness – no rigidity•   Papilloedema in < 1%•   Retinal hemorrhages – 15 %•   Pupi...
OTHER CAUSES OF NEUROLOGICAL                     DYSFUNCTIONVery high fever – febrile seizures, altered consciousness,Psyc...
Decerebrate and Decorticate rigidity11/25/2010               Cerebral malaria           13
Assymetric gaze and opisthotonus11/25/2010               Cerebral malaria       14
SEQUELE AND POST MALARIAL NEUROLOGICAL                      SYNDROMES3% in adults, 10% in children.     50% recover comple...
InvestigaionsMicroscopic examination of blood film is gold standard for diagnosis ofmalaria.•Thick blood film    – Species...
Microscopy• Thin blood film                         • Thick blood filmSchizonts         Trophozoite             Gamatocyte...
Treatment•   Medical emergency Requires ICU care.•   Ventilatory support, cardiac monitoring.•   Correction of fluids, ele...
CONCLUSION•     Changing profile of clinical features of plasmodium      falciparum – cerebral malaria jaundice / renal fa...
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Cerebral Malaria

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  • cerebral malaria
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  • Transcript of "Cerebral Malaria "

    1. 1. Cerebral malaria By Dr Ranganath Koggnur S11/25/2010 Cerebral malaria 1
    2. 2. Objectives • Definition • Epidemiology • Pathophysiology • Clinical features • Investigations • Treatment • Conclusion11/25/2010 Cerebral malaria 2
    3. 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)11/25/2010 Cerebral malaria 3
    4. 4. EpidemiologyWORLD 300 – 500 million cases ( 90% in Africa) 1.1 - 2.7 million deaths annuallyINDIA 2.5 – 3 million cases / yr 1000 deaths / yr ( under estimate )11/25/2010 Cerebral malaria 4
    5. 5. PATHOGENESIS OF CEREBRAL MALARIA1. MECHANICAL HYPOTHESIS Sequestration of RBC in the brain by cytoadherence / Rosetting2. Toxin/cytokine HYPOTHESIS Malarial toxin induced cytokines stimulating excessive Nitric oxide Production.11/25/2010 Cerebral malaria 5
    6. 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.11/25/2010 Cerebral malaria 6
    7. 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.11/25/2010 Cerebral malaria 7
    8. 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 ) ↓ COMA11/25/2010 Cerebral malaria 8
    9. 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.11/25/2010 Cerebral malaria 9
    10. 10. CLINICAL FEATURESOnset Acute – following seizures GradualConsciousness Drowsiness, confusion, disorientation, delirium and agitation.Seizures Repeated genaralised convulsions > 2/24 hrs.11/25/2010 Cerebral malaria 10
    11. 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 variable11/25/2010 Cerebral malaria 11
    12. 12. OTHER CAUSES OF NEUROLOGICAL DYSFUNCTIONVery high fever – febrile seizures, altered consciousness,Psychosis.Antimalarial drugs – chloroquine, mefloquine.HYPOGLYCEMIA – severe parasitemia,quinine.Hyponatremia – vomiting, elderly patients.Severe anemia11/25/2010 Cerebral malaria 12
    13. 13. Decerebrate and Decorticate rigidity11/25/2010 Cerebral malaria 13
    14. 14. Assymetric gaze and opisthotonus11/25/2010 Cerebral malaria 14
    15. 15. SEQUELE AND POST MALARIAL NEUROLOGICAL SYNDROMES3% 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. 11/25/2010 Cerebral malaria 15
    16. 16. InvestigaionsMicroscopic examination of blood film is gold standard for diagnosis ofmalaria.•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 24hrs11/25/2010 Cerebral malaria 16
    17. 17. Microscopy• Thin blood film • Thick blood filmSchizonts Trophozoite Gamatocytes Schizonts11/25/2010 Cerebral malaria 17
    18. 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 THERAPY11/25/2010 Cerebral malaria 18
    19. 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.11/25/2010 Cerebral malaria 19

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