1. ACUTE VIRAL
ENCEPHALITIS IN
CHILDREN
Dr D Kalpana, M.D(ped), D.M(Neuro), D.N.B (Neuro)
Sr. Consultant Pediatric Neurologist, KIMSHEALTH, Thiruvananthapuram, Kerala.

2. OUTLINE
• Definitions
• History
• Epidemiology
• Diagnostic approach
• Outline of management
• Prevention

6. WHO DEFINITION
• Used for syndromic surveillance in the context of JE
• Includes all etiologies of fever & altered sensorium - Infectious
, post infectious (ADEM, Autoimmune encephalitis) and non
infectious (toxins, metabolic, and endocrine causes)
• Systemic infections may cause encephalopathy without direct
CNS infection or inflammation of brain tissue(Septic
encephalopathy)
• Accurate diagnosis of underlying disease essential
6

7. DIAGNOSTIC CRITERIA FOR ENCEPHALITIS
(International consortium for encephalitis 2013)
Major criteria
• altered mental status
consisting of altered level of
consciousness , lethargy
• personality change
• for 24 hours
• with no alternate cause
identified
• Minor criteria (2 required for possible; 3 required for
probable/confirmed encephalitis)
1. Fever 380 C
2. New-onset seizures (not due to prior
seizure disorder)
3. New onset of FND
4. CSF white blood cell count > 5
cells/mm3
5. Abnormal neuroimaging
6. EEG demonstrates abnormality
consistent with encephalitis
7

8. EPIDEMIOLOGY
• Incidence – 1.5 to 7 per 1,00,000 population every year
• No etiology is identified in about 40% of cases even in US
• Viruses are the most common pathogen identified
• In adults Herpes simplex virus is the most common virus identified in US.
Followed by enterovirus, varicella zoster and arboviruses
• In India Japanese Encephalitis is the most common pathogen which
causes epidemics
• JE was identified in 1955, as a cause of encephalitis in India(Vellore)

9. HISTORY OF AES IN INDIA
• Phase I : before 1975 few cases of AES due to JEV identified
• Phase II : 1975 to1999 .More JEV cases were reported
• with frequent outbreaks or epidemics
• development of JE endemic regions near the Gangetic plains and in
parts of Deccan and Tamil Nadu, Kerala.
• Phase III : 2000- 2010, rise in non-JE outbreaks mostly caused
by viruses such as Chandipura virus (CHPV),Nipah virus (NiV),
and other enteroviruses
9

10. HISTORY OF AES IN INDIA
• After 2012: shift towards JE
• Indian states of UP , Bihar, Assam, WB ,
and TN identified as JE endemic zones
• Encephalitis outbreak from Bihar : Initial
suspicion of a new virus
• later detected to be an
encephalopathy with hypoglycaemia.
• toxin prevalent in the litchi fruit
(methylene cyclopropyl glycine due to use of
alpha cypermethrin above the
minimum safety levels)
10

11. OUTBREAK DATA FROM INDIAN STATES
• 2013: 2,205 JE,death -590
• 2014 data
• UP (3,329 cases, 627 deaths)
• Assam (2,194 cases, 360 deaths)
• West Bengal (2,381 cases, 169 deaths)
• Bihar (1,385 cases, 355 deaths)
• During 2018, in Kerala 23 cases of NiV(Nipah Virus) were identified, 18 lab
confirmed, case-fatality rate - 91%, ( 21 death)
11

12. VIRAL ENCEPHALITIS
RNA Virus
• JE
• WNV
• Dengue
• Chikungunya
• Nipah
DNA Virus
• HSV I & II
• VZV
• HHV-6
• Adeno
• Parvo
• EBV
• CMV
12
• KFD
• Chandipura
• Entero
• Rabies
• LCMV

13. APPROACH TO DIAGNOSIS
History
• Geographical location
• Season
• Any epidemic going on in that area
• Death of pigs, ducks in large numbers,
• h/o animal bites
• Gastrointestinal symptoms
• Skin rashes
• Immune status of the child

16. • H

18. SKIN AND MUCOSAL FINDINGS
Generalized Maculo-papular rash
• EBV
• Measles
• HHV-6( Roseola)
• WNV
• Dengue
• LCMV-Occasional
18

20. HERPES SIMPLEX VIRUS
• Single most common cause of
sporadic encephalitis world wide
• Bimodal age distribution
• HSV -1 in adults, HSV-2 Neonates
• predilection for selective brain
regions (focal encephalitis)
• Mostly unilateral - the anterior and
medial temporal lobe, inferior frontal
lobe, insular cortex, thalamus
• Brainstem encephalitis is possible
but uncommon
• Mortality <15% with Acyclovir
• Sequele: epilepsy, , long-term
neuropsychiatric deficits
• Anti NMDAR encephalitis can
follow HSV encephalitis
20

21. HSE
21

23. VARICELLA ZOSTER VIRUS
 Usually occurs a week after primary chickenpox rash
 Most common presentation as cerebellar ataxia, but may
also cause more diffuse encephalitis
 Primarily result from virus associated vasculopathy
23

25. VZV
25

26. EBV
occurs during primary EBV infection in children or
young adults, and is associated with nonspecific
systemic symptoms, such as fever, or frank IMN
Fever, lymphadenopathy, rashes, may be seen, but not
always
Features: seizures, confusion, “Alice in Wonderland”
syndrome, hemorrhagic meningoencephalitis
26

27. EBV
27

28. HHV-6
 Mostly occurs before age of 2 years
 a frequent cause of febrile seizures
 may also cause encephalitis with altered behavior, reduced consciousness,
and sometimes brainstem manifestations.
 Neurologic manifestations occur during the febrile period of infection,
sometimes before development of the characteristic rash of roseola
infantum
 good recovery
 In immuno-compromised adults ( post-transplant limbic encephalitis)
28

29. ARBOVIRUSES
 Neurologic symptoms usually emerge after a systemic
infectious prodrome
 can cause meningitis and/or encephalitis
 less frequently can affect the peripheral nerves or spinal
cord with a predilection for the AHC
 Can manifesting as AFP
29

30. JAPANESE ENCEPHALITIS
 most common cause of infectious encephalitis worldwide
esp south -east Asia
 predominantly affects children and young adults
 Seizures occur in most cases
 Extrapyramidal features, such as masklike facies, tremor,
rigidity are also common as a subacute or chronic
manifestation.
30

31. WEST NILE VIRUS
• common in India
• geographic prevalence & quantitative contribution to
acute encephalitis in India have not been systematically
studied
• fever, fatigue, headache, myalgia,  a diffuse non-pruritic
MP rash
• Extrapyramidal symptoms
31

32. WEST NILE VIRUS
• Encephalitis (50% to 60% of
neuroinvasive infections)
• predilection for the brainstem - coma
as an early manifestation, can affect
the basal ganglia, thalamus, and
cerebellum
• Movement disorders,- tremor,
dyskinesia, myoclonus, parkinsonism
frequent
• Mild weakness or hyporeflexia
without full-blown AFP (AHC
infection )
• Optic neuropathy & other cranial
neuropathies can be present
32

33. WNV
33

34. OTHER ARBO VIRUS IN ASIA ,AFRICA, SOUTH
AMERICA
• Dengue virus common in India, China, South-East Asia, Africa, and Central and
South America
• Neurologic manifestations in <10% of patients
• Chikungunya virus : similar geographic distribution as dengue virus
• CNS involvement is rare but encephalitis, encephalopathy, meningitis, and optic
neuropathy have all been reported
• Zika virus, important emerging virus, but presentation not as AES
34

35. “DOUBLE DOUGH NUT SIGN” IN DENGUE
ENCEPHALITIS

36. ARBOVIRUSES IN NORTH AMERICA
• WNV: mot common in North America
• La Crosse encephalitis: in eastern parts,
mild , low mortality, Seizures in 50%
• St. Louis encephalitis: outbreak pattern
• Eastern equine encephalitis in eastern
regions , severe encehalitis with
mortality is around 40%.
• Jamestown Canyon virus -mild
encephalitis, often in older people
• Powassan virus: North-Eastern and
Midwest states, frequently in older age
groups.
• causes a severe encephalitis, 10%
mortality rate
• long-term neurologic deficits in 50%
survivors( Oculomotor abn and
hemiplegia)
36

37. ENTEROVIRUSES & PARECHOVIRUSES
• most frequent in children
• encephalitis causing strains
• EV-D 68, 71, 75, 76 & 89
• coxsackie virus A9 & A10
• Echovirus 4, 5, 9, 11, 19 & 30;
• Human parechovirus 3
37

38. EV INFECTIONS
• usually occur in outbreaks
• spread - fecal-oral or
respiratory
• young children
• Features : pharyngitis, GI
illness, hand-foot-and-
mouth disease, or
herpangina
• Encephalitis in <30%
patients , mild (
• altered sensorium, seizures
,FND)
• EV-71 and EV-D68
• more severe neurologic
manifestations
• EV-71 & EV-D68 can cause a severe
brainstem encephalitis
• cranial nerve palsies, myoclonus,
ataxia, and respiratory depression
• AFP with encephalitis or in isolation
• Neurological sequele +
• Mortality 14%
38

39. ENTERO VIRUS RHOMBENCEPHALITIS
39

40. RABIES VIRUS
• Rabies virus is transmitted from an animal bite
• travels to the CNS trans-synaptically.
• still common in regions of Africa and Asia.
• Feature : early limbic encephalitis(furious rabies) , or as early radiculomyelitis (paralytic rabies
)
• .As the infection progresses encephalitis ensues in all patients.
• prodromal symptoms of mild weakness and neuropathic pain in the bitten extremity
• neurologic features include agitation, hydrophobia, aerophobia, fluctuating consciousness,
inspiratory spasms, and autonomic disturbance
• As the disease evolves, patients become comatose with flaccid paralysis.
40

41. RABIES
41

42. MUMPS AND MEASLES
• affect children and young adults
• Reduced incidence due to vaccination
• Mumps: Meningitis (<10% ), encephalitis
(0.1%), usually mild
• rarely severe -seizures, movt disorders, BS
signs , cortical blindness
• Systemic features +
• Acute measles encephalitis
• <0.3% of primary measles
• During phase of
morbilliform rash
• Rash not be present
in all cases of encephalitis
• usually severe
• seizures, coma, FNDICP
• Mortality -15%
• 25% survivors have sequele
( epilepsy ,
developmental delay)
42

43. HENIPAH VIRUSES
• Hendra and Nipah viruses
• Zoonotic
• Bats viral reservoir for both
• Hendra virus is transmitted from bats to horses.
• Nipah virus is transmitted to humans in the same manner via pigs.
• Rarely acquired by humans from contact with secretions/excretions of infected
horses/pigs/ bat bitten fruits
43

44. NIPAH VIRUSES
• severe encephalitis
• associated with influenza-like or respiratory illness
• Abnormal brainstem reflexes, autonomic
disturbance,(tachycardia, hypertension) segmental myoclonus,
seizures, and cerebellar signs are characteristic features common
with Nipah virus encephalitis
• Mortality of 40% to 70%
44

45. EBOLA VIRUS
• highly contagious infection
• largest epidemic in West Africa (2013 –
2016)
• acquired via direct contact with bodily fluids
or tissue of an infected animal or human
premortem or postmortem
• severe systemic features- fever,
profuse diarrhea, vomiting
,hypovolemic shock.
• hemorrhagic complications
• encephalitis or meningoencephalitis
reported sometimes
• occur in late course
• altered mental status, behavioral
disturbance, hallucinations, headache,
seizures, meningismus, tinnitus, hearing
loss, and blindness
• Mortality up to 90%,mostly due to
severe systemic complications
45

46. INFLUENZA
• Neurologic complications rare
• occur most frequently with influenza A, H1 N1
• encephalopathy /encephalitis most frequently reportedin children
in East Asia and Australia
• Elderly, pregnant ladies and patients with pre-existing neurologic
disease also susceptible
46

47. INFLUENZA
• An acute viral illness usually precedes neurologic manifestations
• Encephalopathy : Fever, altered consciousness, seizures, and vomiting in 9% to 37%
patients
• ataxia and focal neurologic deficits
• Severe syndrome of acute necrotizing encephalitis characterized by bilateral,
frequently hemorrhagic, thalamic lesions
•
• Syndrome mild encephalopathy with reversible splenial lesion
47

48. ANE
48

49. 49
BOOMARANG SIGN

50. DIAGNOSTIC APPROACH
• encephalitis vs differential etiology
• If encephalitis: infectious vs auto immune
• associated fever, rash, gastrointestinal, or respiratory symptoms favours infectious
cause
• But fever & movement disorders or FBD seizures may be characteristic of anti-
NMDARE or anti-LGI autoimmune encephalitis.
• presentation often nonspecific and both categories of encephalitis need to be
considered in the initial diagnostic evaluation
50

51. DIAGNOSTIC EVALUATION IN SUSPECTED VIRAL
ENCEPHALITIS
• Brain Imaging (MRI with Contrast if possible)
• Spinal imaging if associated myelopathy / radiculopathy
• Inability to perform imaging in critically ill patient should not delay
CSF study unless clinical features of impending herniation present
• Guarded LP after controlling cerebral edema should be attempted if
MRI /CT not possible
51

52. CSF
• Opening pressure
• Cell counts & WBC differential, protein & glucose
• Gram stain & Bacterial culture
• HSV 1& 2, VZV & EV PCR
• HSV 1 & 2, VZV Ig if > 1week
• Neural Specific auto Ab
• Additional studies for potential organisms
• OCB, Ig G index
Freeze extra sample for later testing
52

53. TARGETED TESTS OF SERUM AND CSF FOR
SUSPECTED VIRUSES
• EBV, HHV-6
• Arbo Viruses based on geographic location, season, vector exposure
• Mumps, measles , influenza based on clnical features and suspected contacts
• Henipa virus: based on region & animal exposure
• Consider other bacterial & fungal encephalitis
53

54. BLOOD INVESTIGATIONS
• Bacterial culture
• HIV serology
• Dengue PCR, NS 1 Ag
• Paired sera for JE Ig
• Serology for Leptospira, Scrub typhus
• Neural specific auto antibodies
• Additional studies according to potential organisms
• Store serum sample for later testing
54

55. ADJUVANT TESTS
• EEG :, PLEDs, Slowing, NCSE, extreme Delta Brushes
• Samples from associated sites of infection : Throat swab, stool culture, Stool EV
PCR
55

65. TREATMENT
• Initial treatment regime should broadly cover treatable infections with
subsequent narrowing to the suspected dx
• All patients presenting with a syndrome suggestive of AES should be treated
empirically with acyclovir (for HSV and VZV encephalitis)
• if there is any suspicion for a bacterial meningoencephalitis then third-generation
cephalosporin  Vancomycin
65

66. TREATMENT
• HSV, VZV: IV Acyclovir 10mg /kg 8th hrly X 14-21 days (Neonates : 20mg/kg)
• Oseltamivir : ? Effect on CNS outcome
• WNV: possible role for IVIG (particularly if pooled from endemic populations with
high levels of anti–WNV Ab )
• Azithromycin, Doxycycline : Mycoplasma, Scrub typhus
• Leptospira: Penicillin
• IVIG, IVMP, Plasmapheresis: ADEM/ Auto immune encephalitis
66

67. POST INFECTIOUS AUTOIMMUNITY
• ADEM: 1st episode of acute encephalopathy and multifocal CNS demyelination,
with no new symptoms, signs, or MRI findings 3 months after onset
• CSF studies :mild lymphocytic pleocytosis
• MRI brain : multifocal T2-hyperintense lesions measuring 5 mm to 50 mm, with some
or all lesions enhancing
• Myelitis : longitudinally extensive
• Relapsing or multiphasic ADEM : in up to 10% , NMOSD , MOG-Ab related
syndromes or MS
67

68. PREVENTION
• General measures
 Vector control measures
 Prevention of feco oral transmission in enteroviruses
 vaccination of pet dogs and cats
 Providing shelter for stray dogs, vaccination, sterilisation

69. VACCINATION
• JE Vaccination : affected districts brought under vaccination as part of UIP
• Live attenuated 14-2-2
• children bw 1-15 years,
• The vaccine efficacy is about 100% after two doses when administered at one or two years of age
• VZV Vaccination : live attenuated vaccine for mainly children : 2 doses
• MR and MMR vaccines
• Anti rabies vaccine – pre and post exposure prophylaxis
• Yearly Influenza vaccine
• Dengue vaccine
69

70. CONCLUSION
• Viral encephalitis accounts for 30-50% of AES
• Common clinical features + with few exceptions
• Imaging findings and EEG often give clues to the etiology
• Specific diagnoses often made by viral PCR film array, IgM/IgG antibodies in
serum/CSF
• Non viral causes like cerebral malaria, tuberculous meningitis, leptospirosis,
rickettsial and mycoplasma infections should not be missed as they have specific
treatment
• Non infectious etiologies like ADEM and Autoimmune encephalitis also are
eminently treatable

71. CONCLUSION
• Symptomatic and supportive care including
• Management of cerebral edema
• Fluid and electrolyte correction
• Seizure/ Status management
• Specific treatment is available against only a few viruses
• Symptomatic and supportive management helps A LOT in improving prognosis
and outcome

72. THANK YOU