This document provides guidance on the management of acute encephalitis. It defines encephalitis and related terms. The causes of acute encephalitis syndrome are discussed, including various viral, bacterial, and non-infectious etiologies. Signs and symptoms as well as clues from physical examination are outlined. A 6-step approach to evaluation and management is then described: 1) rapid assessment and stabilization, 2) clinical evaluation, 3) investigations such as CSF analysis and imaging, 4) empirical treatment, 5) supportive care and treatment, and 6) managing complications and rehabilitation. Key challenges in management are also reviewed.

1. Management of Acute
Encephalitis
Dr. Kiran Rajput
Guide - Dr. Pradeep Pazare
1

2. 2
DefinitionDefinition
• Encephalitis is an acute inflammatory
process involving brain tissue with
dysfunction of brain(diagnosis is strictly
histopathological but clinical/imaging markers
may provide evidence of inflammation)
• Meningoencephalitis is an acute
inflammatory process involving the meninges and, to
a variable degree, brain tissue.
• They are often found associated together.

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EncephalopathyEncephalopathy
Encephalopathy describes a clinical
syndrome of altered mental status,
manifesting as reduced consciousness or
altered behaviour without inflammation.

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Acute Encephalitis SyndromeAcute Encephalitis Syndrome (AES)
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)

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Causes of AESCauses of AES
• Viral encephalitis,
• Acute Pyogenic Meningitis,
• TBM,
• Cerebral Malaria,
• Acute Disseminated Encephalomyelitis (ADEM).

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Non-infective causes of epidemic AESNon-infective causes of epidemic AES
• Plant toxins
• Heat stroke,
• Reye’s syndrome.

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Causes of Encephalitis
• Infectious causes:
– Viral
– Bacterial (TBM)
– Ricketssial,
– Fungal,
– Parasites (pl falciparum)
• Non-infectious causes.

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

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Viral CausesViral Causes (continued)(continued)
• Dengue Virus,
• Measles virus,
• Chandipura virus:
– Outbreak: AP 2003, GJ 2004, Nagpur 2005 & 2007.
– Sporadic: AP 2005-2006.

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

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

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

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

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

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

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Clinical FeaturesClinical Features (continued)
• Behavioural changes,
• Impairment of consciousness,
• Focal neurological signs,
• Seizures.

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

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Encephalitis associated with
respiratory illness
• Influenza viruses:
• Paramyxoviruses,
• Bacteria.

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

20. 20
CluesClues (continued)(continued)
• Skin rash:Skin rash:
– Meningococcemia,
– Dengue,
– Measles,
– Varicella,
– Rickettsial diseases,
– Arboviral diseases,
– Enteroviral encephalitis.

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RickettsiaRickettsia
MenigoccocemiaMenigoccocemia
DengueDengue
MeaslesMeasles

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

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CluesClues (continued)(continued)
• Orchitis:
– Mumps
• Labial herpes in young children:
– Herpes simplex virus encephalitis.

24. Etiological agent based on clinical
presentation
• DEMENTIA Measles HIV
• Cerebellar ataxia VZV
• Retinitis CMV
• Lymphadenopathy HIV EBV CMV Measles Rubella
• Extrapyramidal manifestations: Japanese B virus, West Nile
virus, Nipah virus
• Diarrhea: Enterovirus
• Poliomyelitis like flaccid paralysis :Japanese B virus
poliovirus enterovirus West Nile virus Tick-borne encephalitis virus
• Respiratory tract infection : H1N1
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25. DIFFERNTIAL DIAGNOSIS:
• Autoimmune Encephalitis
• Sjogren Syndrome
• Hashimoto’s Thyroiditis
• SLE
• ADEM
• Vasculitis Of CNS
• Reye’s Syndrome
• Metabolic and Toxic diseases
• Nonconvulsive status
• Primary and metastatic brain tumors
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26. LUMBAR PUNCTURE
CONTRAINDICATIONS
Imaging Before LP In Raised ICT

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

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ManagementManagement

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Problems encountered in managemntProblems encountered in managemnt
• Paucity of data about the regional
epidemiology and etiology of viral
encephalitis.
• Lack of easily available, low-cost
microbiological testing for agents of viral
encephalitis.
• Lack of specific treatment for majority of
etiological agents.

32. 32
ProblemsProblems (continued)
• High incidence of mimickers:
– Pyogenic meningitis,
– Cerebral malaria,
– TBM,
– Acute Disseminated Encephalomyelitis (ADEM).
• Lack of facility for intensive care in periphery.

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ProblemsProblems (continued)
• Lack of facility for neuroimaging in periphery.
• Patient delay in seeking health care.
• Delay/not performing lumbar puncture.
• Inappropriate supportive care.

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ProblemsProblems (continued)
Inappropriate response during epidemic:
• What samples to take?
• How to store?
• Whom to inform?

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Steps of evaluationSteps of evaluation
and managementand management

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6 steps6 steps
• Step 1: Rapid assessment and stabilization.
• Step 2:Step 2: Clinical evaluation:
– History & Physical Examination.
• Step 3:Step 3: Investigations.
• Step 4:Step 4: Empirical Treatment
• Step 5:Step 5: Supportive care and treatment.
• Step 6:Step 6: Complications and Rehabilitation.

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1 2 3 4 5
6
Eyes
Does not
open eyes
Opens eyes in
response to
painful stimuli
Opens eyes in
response to
speech
Opens eyes
spontaneously
N/A N/A
Verbal
No verbal
response
Inconsolable,
agitated
Inconsistently
inconsolable,
moaning
Cries but
consolable,
inappropriate
interactions
Smiles, orients to
sounds, follows
objects, interacts
N/A
Motor
No motor
response
Extension to
pain
decerebrate
response
Abnormal
flexion to pain
for an infant
decorticate
response
Infant withdraws
from pain
Infant withdraws
from touch
Infant moves
spontaneously or
purposefully
GCSGCS

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Step 1: Rapid Assessment & StabilizationStep 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.

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Step 1Step 1 (continued)(continued)
•Treat/Prevent hypoglycemia.
•Identify signs of cerebral herniation and raised ICP.
•Manage fever.
•Control seizure.
•Correct acid-base and electrolyte imbalance, if any.

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

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HistoryHistory
• 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?

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Physical ExaminationPhysical Examination
• Vitals, GPE, and Systemic,
• Thorough CNS evaluation,
• GCS,GCS,
• Pupil:
– size, shape, symmetry, and response to light.

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Clue!Clue!
Unilateral pupillary dilatation in the
comatose patient should be
considered as evidence of 3rd
Nerve
compression from ipsilateral uncal
herniation, unless proved otherwise.

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Bickerstaff Brain-Stem EncephalitisBickerstaff Brain-Stem Encephalitis
Symptoms of progressive symmetrical
external ophthalmoplegia suggest
Bickerstaff brainstem encephalitis in
association with M. pneumoniae, and can
serve as a clue to the diagnosis,
especially when associated with ataxia.

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Herpes simplex encephalitis (HSE)Herpes simplex encephalitis (HSE)
• Personality changes, confusion, and
disorientation.
• Herpes labialis,
• Focal seizures,
• Unilateral neurological findings,
• Normal CT in first 4-6 days.
• MRI and FLAIR more reliable.
• Positive CSF PCR.

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FundusFundus
• Papilloedema,
• Haemorrhage (Clue for CM)

47. 47
Look for!Look for!
• Hepato-splenomegaly,
• Myocarditis
– (An important complication of EV 71 encephalitis)

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

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

50. 50
CSFCSF
• Gross appearance: colour, transparency
• Chemistry including CSF: Blood Sugar,
• Cytology,
• C/S,
• Latex Agglutination,
• PCR for HSV 1 & 2,
• IgM antibodies for JE & Dengue.

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52. 52

53. Investigation in immunocompromised
patients with altered consciousness
• CSF PCR for HSV, CMV, EBV, VZV,HHV-
6and-7 Influenza, ParvovirusB19
• CSF AFB staining for M. tuberculosis
• CSF culture for L. monocytogens
• Blood culture
• Indian ink staining and if positive cryptococcal
antigen testing in CSF
• Antibody testing and if positive CSF PCR for T.
gondii
• Antibody testing of serum and if positive CSF for
syphilis
53

54. 54
Step 4: Empirical TreatmentStep 4: Empirical Treatment
• Do not wait for report, start treatment
immediately.
• Ceftriaxone + Acyclovir + Artesunate
(stop artesunate if P/S and RDT are
negative).

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Step 5: Supportive Care & TreatmentStep 5: Supportive Care & Treatment
1. Maintain airway, breathing and circulation.
2. Control of seizures.
3. Treatment of raised ICT.
4. Manage fever ((Never give aspirin)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.

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Features of raised ICPFeatures of raised ICP

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5th
centile of systolic BP
Neonate= 60 mmHg
1mo-1yr = 70 mmHg
2-10yr =70+age(yr)x2
>10 yr = > 90 mmHg

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59. 59

60. 60

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62. 62
Specific Treatment
• Until a bacterial cause is excluded, parenteral antibiotics
therapy should be administered:
– Age 0 to 3 months:
• Inj. Cefotaxime + Inj. Ampicillin.
– Age 3 months to 12 years:
• Inj. Ceftriaxone/Inj. Cefotaxime/Inj. Ampicillin + Inj. Chloramphenicol.
• T/T for HSV:
– 3month to 12 yr Inj. Acyclovir 500 mg/m2 8 hrly
– >12yrs 10mg/kg 8 hrly
Duration
Confirmed cases for 14 to 21 days iv treatment and minimum 21
days for those aged 3month-12yr

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Role of Antibiotics
• Under most situations, it may be nearly
impossible to rule out a bacterial infection.
• Incidence of super-added bacterial infection
is high.
• Therefore, a good antibiotic shield is
recommended.

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Dosage
• Inj. Chloramphenicol:
– 100 mg/kg/day in 4 divided doses for 10 days.
• Inj. Ceftriaxone:
– 100 mg/kg/day in 2 divided doses for 10 days.
• Inj. Cefotaxime:
– 200 mg/kg/day in 3-4 divided doses for 10-14 days..
• Inj. Ampicillin:
– 300 mg/kg/day in 4 divided doses for 10 days.

65. 65
Step 6: Prevention/Treatment ofStep 6: Prevention/Treatment of
complications and rehabilitationcomplications 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.

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

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PreventionPrevention

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

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

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IAP RecommendationIAP Recommendation
• JE vaccine not recommended for
routine use.
• Needed only for individuals living in
endemic area.

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VaccinesVaccines
• Inactivated Mouse Brain Vaccine (JE-VAXJE-VAX), not in India
• Inactivated Primary Hamster Kidney Cells-P3-China,
• Live Attenuated Primary Hamster Kidney (PHK) Cells-
SA14-14-2SA14-14-2 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)

72. 72
Live Attenuated SA-14-14-2 Vaccine
• The IAP thinks there is a need of a second
dose of the vaccine to provide more complete
and sustained protection.
• 1st
dose at 9 months along with Measles
vaccine.
• 2nd
dose at 16 to 18 months at the time of 1st
booster of DPT vaccine.

73. 73
Dosage (SA-14-14-2)Dosage (SA-14-14-2)
• Amount: 0.5 ml
• Route: SC
• Single dose between 1 and 15 years of age.
• UIP: 16 – 18 months with 1st
booster of DPT.
• Store at 80
C
• Protect from sunlight
• Efficacy- 94.5%

74. 74
Inactivated Vero Cell culture-derived Kolar
strain, 821564XY, JE Vaccine (JENVAC)
• 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.

75. 75
JENVAC (Kolar Strain)JENVAC (Kolar Strain)
• Lacks the experience of multinational trials,
• 2 doses of the vaccine, 0.5 ml IM at 4 weeks
interval for the primary immunization for
children ≥≥ 1 year of age.
• Need of booster dose at later stage (further
study required for exact timing).

76. IN A NUTSHELL
• Inadequately investigated and managed
• MRI and CT mandatory. PCR testing attempted.
• Supportive therapy mainstay.
• Treatable DD should always be considered.
• Acyclovir should be given empirical therapy.
• Once etiological agent of encephalitis identified
antimicrobial therapy targeted to that infectious agent.
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78. Thank You
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