gen approach of acute encephalitis syndrome

1. Acute Encephalitis syndrome
1
Presenter; Dr. Sachin giri
Gen Medicine
Moderator; Dr A.C. Shrivastava

2. Definition
2
• TheEncephalitis is an acute inflammatory
process involving brain tissue.
• Meningoencephalitis is an acute
inflammatory process involving the meninges and, to
a variable degree, brain tissue.
• They are often found associated together.

3. Encephalitis
3
Two Components:
1. Inflammation of brain, and
2. Dysfunction ofbrain.

5. Encephalopathy
5
• Encephalopathy describes a clinical
syndrome of altered mental status,
manifesting as reduced consciousness or
altered behaviour.

6. Causes of Encephalopathy
6
• Systemic infection,
• Metabolic derangement (e.g. DKA),
• Toxins,
• Drugs & Poisoning,
• Hypoxia,
• Trauma,
• Vasculitis,
• CNS infection.

7. Acute Encephalitis Syndrome (AES)
7
Clinically, a case of acute encephalitis
syndrome is defined as a person of any age, at
any time of year with the acute onset of fever
and a change in mental status (including
symptoms such as confusion, disorientation,
coma or inability to talk) AND/OR new onset of
seizures (excluding simple febrile seizures)

8. Causes of AES
8
Infectious cause
• Viral encephalitis,
• Acute Pyogenic Meningitis,
• TBM,
• Cerebral Malaria,
• Acute Disseminated Encephalomyelitis (ADE).

9. Causes…..
Srtuctural CNS lesions
•Hypothalamic lesion
•Brain stem lesion
•Intraventricular /SAH
•Cerebral venous sinus thrombosis

10. Non-infective causes of epidemic AES
• Plant toxins
• Neuroleptic malignant syndrome
• Heat stroke
• Malignant hyperthermia
• Reye’s syndrome.
• Thyrotoxic encephalopathy
10

11. Causes of Encephalitis
11
• Infectious causes:
• Viral
• Bacterial (TBM)
• Ricketssial,
• Fungal
• Parasites
Pl. falciparum
Protozoal(Naegleria,Acanthamoeba,
balamuthia )

12. VIRAL CAUSES
12
• Enteroviruses: More than 80% of all cases.
• Arboviruses: e.g. Japanese-B Encephalitis which is
more common during summer months.
• Herpesvirus.
• CMV.
• EBV.
• Mumps.
• RSV, Rubeola, Rubella or Rabies (Occasionally).

13. Viral Causes (continued)
13
• Dengue Virus,
• Measles virus,
 Chandipura virus:
– Outbreak:
– Sporadic:
 KFD

14. Viral Encephalitis
14
• Direct viral infection:
– Primary Viral Encephalitis.
• Indirect immune mediated mechanism:
– Post-infectious viral encephalitis.

15. Viral Encephalitis
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• Epidemic:
– Japanese Encephalitis,
– Dengue virus.
• Sporadic:
– Herpes simplex Encephalitis,
– Enterovirus (EV71),
– Chandipura virus,
– Nipah virus,
– Chikangunya virus.

16. Other virus causing sporadic encephalitis
• Varicella zoster virus,
• Mumps,
• Human herpesvirus 6 & 7,
• EB Virus,
• Herpes simplex virus.
16

17. Emerging viral agents
17
• Human parvovirus 4,
• West Nile virus,
• Bagaza virus,
• Coxsackie virus.

18. Non-Infectious Causes
18
1.Acute Disseminated Encephalomyelitis
(ADEM),
2.Antibody-associated encephalitis,
3.Allergy: Post Vaccine.
4.Heat Hyperpyrexia.

19. Signs & Symptoms of Encephalitis
• Fever,
• Headache,
• Lethargy,
• Vomiting,
19

20. 20
Continued…
• Behavioural changes,
• Impairment of consciousness,
• Focal neurological signs,
• Seizures.

21. Encephalitis associated with GIT symptoms
21
• Enteroviruses,
• Rotavirus,
• Parechovirus.

22. Encephalitis associated with respiratory illness
• Influenza viruses:
– Myositis may also be associated.
• Paramyxoviruses,
• Bacteria.
22

23. Clue on physical examination
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• Pallor:
– Cerebral Malaria,
• Icterus:
– Leptospirosis,
– Hepatic Encephalopathy,
– Cerebral Malaria.

24. Clues (continued)
24
• Skin rash:
– Meningococcemia,
– Dengue,
– Measles,
– Varicella,
– Rickettsial diseases,
– Arboviral diseases,
– Enteroviral encephalitis.

25. Clues (continued)
25
• Petechiae:
– Meningococcemia,
– Dengue,
– Viral Hemorrhagic Fever,
• Parotid swelling:
– Mumps.

26. Clues (continued)
26
• Lymphadenopathy
 EBV,Leptospira,Lymphoma,TB
• Orchitis:
– Mumps
• Labial herpes in young children:
– Herpes simplex virus encephalitis.

27. Investigations
Routine blood examination
Renal function test
Liver function test
Serum electrolytes
PBS for malarial parasites

28. CSF in viral encephalitis
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• Pressure: normal or slightly raised,
• Sugar: normal,
• Cells: acellular (no cell) or mild
leukocytosis (mostly lymphocytes)

29. Imaging
29
• CT Scan:
– Normal.
• MRI:
– Localized areas of inflammation,
– Diffuse brain swelling.

30. Management
30

31. DR. M. S. PRASAD 83
Principles of Management
• Hospitalization.
• Save Life.
• Relieve symptoms.
• Provide specific treatment
• Prevent neurological residues

32. Steps of evaluation
and management
32

33. 6 steps
•Rapid assessment and stabilization.
•Clinical evaluation:
History & PhysicalExamination.
Investigations.
Supportive care and treatment.
Empirical Treatment
Complications and Rehabilitation.
33
• Step 1:
• Step 2:
• Step 3:
• Step 4:
• Step 5:
• Step 6:

34. 34
Step 1: Rapid Assessment & Stabilization
• Maintain ABC.
• Intubate SOS (children with GCS < 8).
• Oxygen.
• Ventilation.
• Establish IV line and take samples.
• Fluid bolus (RL/NS 20 ml/kg) SOS.

35. Step 1 (continued)
35
• Fluid bolus (RL/NS 20 ml/kg) SOS.
• Treat/Prevent hypoglycemia.
• Identify signs of cerebral herniation and raised ICP.
• Manage fever.
• Control seizure.
• Correct acid-base and electrolyte imbalance, if any.

36. Step 2
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• Clinical evaluation:
– History including environmental details and
– Thorough Physical Examination.

37. History
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• Onset & duration,
• Fever, headache, vomiting, diarrhoea,
irritability, seizures, and rash.
• Contact with TB, Chicken Pox, Mumps,
• Place of residence
– Endemic for JE?
– Near rice-field?
– Cattle, Pigs?

38. Physical Examination
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• Vitals, General physical Examination, and
Systemic examination
• Thorough CNS evaluation,
• GCS,
• Pupil:
– size, shape, symmetry, and response tolight.

39. Step 3: Investigations
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• Blood/Serum, Urine,Microscopy
• CXR
• CSF,
• Throat Swab, Nasopharyngeal
Swab,
• MRI (if available), avoid sedation.

40. Basic Investigations
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• CBC including platelet count,
• Blood Glucose,
• Serum Electrolytes,
• Liver & Kidney Function Test,
• Blood C/S,
• ABG,
• P/S for MP.

41. CSF
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• Gross appearance: colour, transparency
• Chemistry : Blood Sugar,Protein
• Cytology,
• C/S,
• Latex Agglutination,
• PCR for HSV 1 & 2,
• IgM antibodies for JE & Dengue.

42. Step 4: Empirical Treatment
42
• Do not wait for report, start treatment
immediately.
• Ceftriaxone + Acyclovir + Artesunate
(stop artesunate if P/S and RDT are
negative).

43. Step 5: Supportive Care & Treatment
43
1. Maintain airway, breathing and circulation.
2. Control of seizures.
3. Treatment of raised ICT.
4. Manage fever (Never give aspirin).
5. Maintain fluid & electrolyte balance.
6. Maintain blood-sugar level.
7. Feeding: NPO initially then NG Tube Feeding.
8. Specific Treatment.
9. Methylprednisolone or dexamethasone must be
given to children with suspected ADEM.

44. 44
Step 6: Prevention/Treatment of
complications and rehabilitation
• Physiotherapy, posture change, prevent bed-
sore and exposure keratitis.
• Prevent complications: aspiration pneumonia,
nosocomial infection, coagulation
disturbances.
• Nutrition: early feeding.
• Psychological support to patient and family.

45. UK Regimen
45
(till culture-report is available)
• Aciclovir: 10 mg/kg 8 hrly
– to cover HSV,
• 3rdgeneration cephalosporin:
– to cover bacterial cause,
• Erythromycin/Azithromycin:
– to cover mycoplasma.

46. Japanese-B
Encephalitis
46

47. Japanese Encephalitis (JE)
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• One of the commonest cause of AES.
• Assam, West Bengal, Uttar Pradesh
and Jharkhand.

48. Japanese Encephalitis (JE)
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• Leading viral cause of acute encephalitis syndrome
(AES) in Asia.
• Primarily affects children under age 15.
• Acute onset, fulminant course, and high mortality &
morbidity.
• 70% of patients either die or survive with long term
neurological disability.

49. JE
49
• Group-B arbovirus (Flavivirus).
• Mosquito borne Encephalitis.
• Transmitted by Culicine (culex) mosquitoes.
• Zoonotic Disease.
• Rice or Pig Farming.
• Peak season: JUN – SEP.

50. Virus
50
• Japanese Encephalitis Virus (JEV),
• Single stranded RNA virus,
• Genus: flaviviridae

51. Emerging Problem in
• West Bengal,
• Bihar,
• Assam,
• Madhya Pradesh,
• Maharastra,
• Manipur,
• Haryana,
• Odisha,
• Goa, and
• Puduchery.
51

52. Spread
52
• Spreads by mosquito bite only,
• Man is an incidental dead end host,
• Man-to-man transmission not reported.

53. Life-cycle of virus
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Pig Mosquito Pig
Bird Mosquito Bird
MAN IS AN INCIDENTAL “DEAD END” HOST

54. 54

55. HOSTS
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• Infected pigs do not manifest any overt
symptoms of illness.
• AMPLIFIER OF VIRUS.
• Others:
– Cattle
– Buffaloes
– Horses
– Birds.

56. Japanese-B Encephalitis
56
• Incubation Period: 5-15 days.
• Ratio of overt disease to unapparent infection =
1:300 to 1: 1000.
• Cases represent tip of iceberg.
• Case Fatality Rate: 10 –70%.
• Incidence: 1- 10/10, 000 population.

57. Pathology
57
• Mosquito bite transmission to man JEV
multiplies Neurologic invasion enters CNS
JEV replicates in endoplasmic reticulum and Golgi
apparatus and destroys them.
• Changes mainly in gray matter.
• Growth of the virus across vascular endothelium
mainly thalamus, basal ganglia, brain-stem,
cerebellum, hippocampus and cerebral cortex.

58. Pathology outside CNS
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• Hyperplasia of germinal centers of lymph-nodes,
• Enlargement of malpigian bodies in spleen.
• Interstitial myocarditis, swelling and hyaline
changes in Kuffer’s cells of liver, pulmonary
interalviolitis, and focal hemorrhages in kidneys.

59. Clinical Features.
59

60. Japanese-B Encephalitis
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Sudden onset with high fever, headache, vomiting,
Mental Confusion, Irritability, Loss of consciousness.
• Severe Encephalomyelitis.
– With Radiculitis.
– Without Radiculitis.

61. 3 Stages
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1. Prodromal Illness [2 - 3 days]
2. Encephalitis stage
• Acute Stage [3 - 4 days]
• Sub-acute Stage [7 - 10 days]
1. Convalescence [4 - 7 weeks]

62. Prodromal Stage
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• High grade fever +/- rigor,
• Headache,
• General malaise,
• Nausea and Vomiting.
• During this stage, a definitive clinical
diagnosis is not possible.

63. Encephalitic Stage
63
•
•
Altered mental status:
– Confusion, agitation, coma
Generalized weakness,
• Hypertonia & Hyper-reflexia,
• Seizures,
• Papilloedema and/or Cranial Nerve
involvement,
• GIT bleed & Pulmonary Hemorrhage.

64. Late Stage
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• Stage of convalescence,
• Recovery,
• Persistence of signs of CNS injury:
– Residual neurologicalimpairments
• Secondary infections are frequent in this stage.

65. Residual neurological impairments
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• Involuntary movements:
– Choreoathetosis or extrapyramidal symptoms,
• Paralysis & Paresis,
• Speech disorders.
• Decorticate or Decerebrate Posturing.
• Post-Encephalitis Cerebral Palsy.

66. DIAGNOSIS
66
• Clinical Manifestations.
• Epidemiology.
• CSF:
– Pleocytosis: Initially Polymorphs then Lymphocytes.
– Increased protein.
– Normal sugar.
• EEG: Diffuse slow-wave activity.
• CT or MRI: Swelling of the brain parenchyma.

67. Diagnosis (Contd)
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• Virus isolation
• Detection of viral component
(antigen detection)
• Viral serology

68. Virus Isolation
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• CSF
• Nasopharynx
• Faeces
• Urine

69. Detection of antigen and specific antibody
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• Nucleic Acid Probe
• PCR
• RIA
• ELISA

70. Viral Serology
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IgM & IgG:
IgM appears early within 2 weeks of infection
IgG appears later, peaking around 8 weeks.

71. Two Samples
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1. Acute Serum (at admission).
2. Convalescent Serum
(after at least four weeks).

72. Differential Diagnosis
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• Polio
• Cerebral Malaria
• TBM.

73. D/D with Febrile Seizure
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• Age:
– Febrile seizures limited to age group from 6
months to 6 years.
– Encephalitis and CM occur at any age.
• Recovery from unconsciousness:
– Patients with febrile seizures become fully
conscious and alert after control of seizure.
– Patients with CM or Encephalitis do not gain
consciousness even after control of seizures.

74. Suspected JE
74
• All cases of Acute Encephalitis Syndrome, i.e.
Any presenting with acute onset of fever, and
altered state of consciousness with or without
seizures.
• Patient regains consciousness after control of seizures in
simple febrile seizure but continues to have altered state of
consciousness in JE.

75. Probable JE
75
A suspected case that occurs in close
geographic and temporal relationship to
a laboratory-confirmed case of JE, in the
context of an outbreak.

76. 76
Confirmed JE
A probable case that has been
confirmed by laboratory tests.

77. Management
77

78. Prognosis
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• Mortality: 10 –70%.
• Mortality highest in age 5 –9 yrs.
• Sequelae: 5 - 70%.

79. Prevention
79

80. Control Measures
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a. Vector Control:
1. Fogging.
1. Indoor mosquito spray
b. Vaccination.

81. Personal Protection
81
• Avoid mosquito bites:
– Use mosquito-net
– House Screening
– Mosquito Repellents.
– Avoid evening outdoor exposure.
– Cover body with clothing
• Vaccination

82. 82
Vaccination
• Vaccination against JE is advised
in endemic areas
• In such areas, it is given routinely
to children above 1 year of age,

83. Vaccines
83
• Inactivated Mouse Brain Vaccine (JE-VAX),
• Inactivated Primary Hamster Kidney Cells-P3-
China,
• Live Attenuated Primary Hamster Kidney (PHK) Cells-
SA14-14-2 strain – China: Marketed for both domestic
use and for use in Nepal, S. Korea, Sri Lanka and India.
• Inactivated Vero Cell Culture Derived SA-14-14-2 JE vaccine
(IC51)-(IXIARO)

84. Live Attenuated SA-14-14-2 Vaccine
84
• Launched in India in 2006.
• Single Dose.
• Efficacy: 94.5%
• JE Vaccine efficacy:
– 60% in UP and 70% in Assam
– Results better in Nepal.

85. Dosage (SA-14-14-2)
85
• Amount: 0.5 ml
• Route: S.C
• Single dose between 1 and 15 years of age.
• Store at 80C
• Protect from sunlight

86. 86
• JENVAC is a Vero Cell culture-derived,
inactivated, adjuvanted and thiomersal
containing vaccine.
• The original virus strain used in the
vaccine was isolated from a patient in
the endemic zone in Kolar, Karnataka,
India.

87. Vaccination
87
• Protective immunity develops in
about a month’s time after the
second dose.
• Revaccination after 3 yrs.
• Best used in inter-epidemic period.

88. THANK YOU….