Encephalitis Overview

1. Encephalitis
Presented by
Dr.Ashish Chowdhury
Phase- B Resident
Dept. Of Neurology, BSMMU

2. Overviews
• Definition
• Etiology- World wide, Bangladesh
• Acute Encephalitis-Introduction of Common
Encephalitis world wide and Bangladesh.
• Investigations, Management, Prognosis Of
Acute Encephalitis
• Autoimmune Encephalitis
• Subacute And Chronic Encephalitis.

3. Definition
• Generalized or focal involvement of brain tissue by an
inflammatory process in the cerebral hemispheres,
cerebellum, or brainstem is referred to as encephalitis.
• Many patients with encephalitis also have evidence of
associated meningitis (meningoencephalitis) in some
cases, involvement of the spinal cord or nerve
roots(encephalomyelitis,encephalomyeloradiculits)

4. Etiology
Viral:
Herpes Group: HSV 1&2, VZV, CMV, EBV, HHV-6
Arbo virus Group:
Alpha virus: EEE, Western EEV
Flavi virus: WNV, Japanese-B EV, St. Louis virus
Dengue, Chikungunya
Entero virus: Echo, Coxsackie
Others: Nipah, H1N1, HIV, Mumps, LCMV, Rabies

5. Bacterial: Mycoplasma, L. Monocytogenes,
Rickettsia, Legionnaire, Lyme disease, Brucella
Others: Protozoa (Negleria fowleri), Fungus,
Helminth, Prion disease
Non infective: Autoimmune encephalitis(Anti
NMDA )

6. Common Causes of Encephalitis In Bangladesh
 Epidemic
 Japanese encephalitis
 Nipah Virus
 Dengue
 Chikungunya
 Sporadic
 Herpes simplex
 Enterovirus
 Mumps
 Varicella zoster
 Measles

7. Surveillance for Encephalitis In
Bangladesh:
• Epidemiology and aetiology of encephalitis
remain largely Unknown in Bangladesh even
in Asia.
• Done by ICDDR,B;CDC,Atlana,USA
• Center: DMCH,RMCH,MMCH
• Duration: June2003 – 10 July,2004
• Total Number Of enrolled Case: 264
• Result shown depending on First 176 cases.

8. Surveillance
• Every Fourth encephalitis patients admitted To
hospital who met the case definition, Proper
Investigations , Clinical and epidemiological data
were Collected.
• Serum , CSF, Saliva, Oropharyngeal swabs, urine and
Stool Samples tested Over 100 pathogens in 12
laboratories at CDC,USA.
• Follow up visit : 4-6 weeks after recruitment into the
Study to evaluate short term Neurological and
functional outcome.
• 25% patient died in hospital or before completing
follow up.

9. Pathogens associated with Study:
• Japanese Encephalitis :(10/176)=6%
• Dengue: 6
• Neisseria meningitidis :11
• Streptococcus Pneumoniae: 7
• HSV: 2
• Mumps: 2
• HHV:1
• EBV :1
• Echovirus:1

10. Clinical Presentation
• Acute febrile illness .
• Altered level of consciousness (confusion, behavioral
abnormalities), or a depressed level of consciousness
ranging from mild lethargy to coma
• Focal deficit : aphasia, ataxia, upper or lower motor
neuron patterns of weakness, involuntary movements
(e.g., myoclonic jerks, tremor), and cranial nerve deficits
(e.g., ocular palsies, facial weakness).

11. Clinical Presentation : contd…
• Patients with encephalitis may have hallucinations,
agitation, personality change, behavioral disorders, and
frank psychotic state.
• Focal or generalized seizures
• Involvement of the hypothalamic-pituitary axis may result
in temperature dysregulation, diabetes insipidus, or the
development of the syndrome of inappropriate secretion
of antidiuretic hormone (SIADH).

12. Differentiating viral Encephalitis from
ADEM
• Direct invasion of brain and meninges (true viral encephalitis)
and a post infectious encephalomyelitis an autoimmune reaction
to the systemic viral infection
• ADEM occurs after a latency of several days to weeks, as the
infectious illness is subsiding.
• Associated features of spinal cord involvement & bilateral optic
neuritis favors ADEM
• There are usually characteristic confluent, scattered, bilateral
lesions in the white matter in imaging studies, findings that differ
from those of viral encephalitis(Focal, grey matter, cortical)

13. Arboviral encephalitis
• Arthropod-borne viruses, mostly Flavi virus
• Transmitted by Mosquito/ tick bite
• Seasonal incidence: limited to the summer and early
fall (August- October)
• Clinical manifestations are almost indistinguishable
• A special syndrome of febrile, flaccid, paralytic
poliomyelitis resulting from West Nile virus
• Proportion of patients: Hyponatremia, raised
intracranial pressure with cerebral swelling

14. • Diagnosed by antiviral immunoglobulin IgM
antibody is present in the serum and CSF
• MRl may be normal or show signal changes and
edema in the cortex, basal ganglia, or thalamus
• No antiviral agents are known to be effective; only
supportive measures

15. Japanese Encephalitis
• Most Common Mosquito borne encephalitis .
• Caused by Group B Flavivirus.
• Endemic In Temperate and Tropical region Of Asia.
• 35000-50000 annual Cases Of which 10000-15000 annual
death world wide.
• First Recognized in 1871 in japan and 1935 Virus Isolated
from Human brain named Nakayama strain, Tokyo ,Japan.
• Transmission Cycles include Mosquitoes( Culex),
Birds,Pigs,Horse.
• Affects All Age Groups, Most Common less than 15 years of
ages.

16. Bangladesh overview
• First Outbreak in Mymensingh in 1977.
• A Novel study estimated the incidence of JE found
rates as high as 2.7 per 100000 population in
Rajshahi divison.
• Outbreaks typically occur during or shortly after the
rainy season .
• UN Data shows "Japanese encephalitis cases"
for Bangladesh contains data from the year 2009
until 2012. 2009-15 cases,2010-15 cases,2011-103
cases,2012-52 cases.
• Environmental Determinant: Irrigated Rice
Agriculture

17. Japanese Encephalitis : contd…
• Incubation period: 6-16 days.
• Infection with JEV is often asymptomatic. Man to
man transmission has not been reported.
• Onset of the illness can be abrupt, acute, sub acute,
or gradual.
• The course of the disease can be conveniently
divided into three stages:
(i) A prodromal stage preceding CNS features
ii) An encephalitis stage marked by CNS Symptoms
(iii) A late stage noticeable by recovery or persistence
of signs of CNS Injury.

18. Japanese Encephalitis : contd…
• CSF: Elevated Protein, Pleocytosis with 10 to 500/μL
early polymorphs later replaced by lymphocyte.
• Specific Diagnosis: IgM Ab in Serum and CSF,Four
fold IgG Ab between acute and convalescent sera.
• Virus Isolation : CSF,Blood.
• MRI :Abnormal signal in thalamus and basal ganglia.
• Fatality : 30-40%
• Neurological Sequelae : Parkinsonism, Seizure
Disorder, Paresis, Mental retardation, Psychiatric
disorder

19. Japanese Encephalitis : contd…
• Treatment: No specific therapy, Supportive
only.
• Prevention: Vaccination-There are two types of
JEV vaccines currently available: 1) inactivated,
mouse brainderived JEV vaccine( Two dose 7-14
days interval, Booster yearly, Revaccination 3yr
interval) 2) live attenuated JEV vaccine
• Vector Controll, Prevention of mosquito bite ,
Protection of reservoir .

20. Herpes Simplex Encephalitis
• Most common, sporadic, all age, throughout the year, all
over world, Gravest, 10% of all encephalitis,30-70% Fatal.
• Predilection for inferomedial or lateral portions of the
frontal and temporal lobes and the insula
• So complex partial seizure, amnesia, personality change,
psychosis, olfactory hallucination
• Hemorrhagic swelling and herniation of temporal lobes
leading to coma

21. Herpes Simplex Encephalitis:contd...
• CSF: lymphocytic pleocytosis, mildly increased protein,
normal glucose, red cell
• Serum & CSF HSV1 , HSV2 antibody, PCR
• MRI shows signal changes in almost all (increased signal in
T2-weighted images), scattered hemorrhage, contrast
enhancement
• EEG changes consisting of lateralized periodic high-voltage
sharp waves in the temporal regions and slow-wave
complexes at regular 2 to 3/s intervals

22. Dengue Encephalitis
• Endemic > 100 countries
• Vector :Aedes aegypti
• Various manifestations, Multisystem
derangement by severe dengue infection causing
cerebral insult.
• Neurotropism
• Clinical features: Fever, Headache, reduce
conciousness, Seizure, meningism, extensor
plantars, frontal release signs, abnormal
posturing, facial nerve palsy, and quadriparesis.
• Others neurologic manifestations : Transverse
myelitis, GBS, ADEM, Myositis

23. • Laboratory diagnosis:
 Detection of viral antigens by immunochemistry-NS1
antigen ( 89% sensitive).
 Viral RNA detection by PCR.
 Viral Culture
 ELISA For dengue IgM Ab
 CSF study
 MRI: general findings consistent with viral encephalitis
include cerebral edema, white matter changes, and
(later) necrosis and brain atrophy. Infarction or
hemorrhage may also be visible.
 Treatment : No Specific therapy
supportive management as dengue

24. Chikungunya Encephalitis
• The possibility of encephalitis may be around one to five
per 1000 chikungunya infections
• Patients who had neurological symptoms at disease
onset and were still affected 3 years later.
• Encephalitis was more likely to occur in young infants
and adults older than 65 years. The incidence rate in
infants was 187 per 100,000 people; it was 37 per
100,000 people in people older than 65 years.
• The death rate for those with chikungunya virus–
associated encephalitis was 16.6%, and 30% to 45% of
those with the disease had persisting disabilities, which
included behavioral changes and problems with thinking
and memory skills in infants

25. • long-term disabilities (lifelong in infants) such as cerebral
palsy, neurocognitive delays and learning difficulties, and
postinfective dementia in older adults.
• There is no vaccine to prevent chikungunya and no
medicine to treat it, people who are traveling to these
areas should be aware of this infection and take steps to
avoid mosquito bites, such as wearing repellent and
long-sleeves .

26. Brainstem Encephalitis
• This presents with ataxia, dysarthria, dysphagia, diplopia
or other cranial nerve palsies.
• The causative agent is presumed to be viral. The CSF is
lymphocytic, with a normal glucose
• However, Listeria monocytogenes may cause a similar
syndrome with meningitis (and often a
polymorphonuclear CSF pleocytosis) and requires
specific treatment with ampicillin 500 mg 4 times daily.

27. Nipah Encephalitis
• Paramyxovirus ,1998, Malaysia, Sungai Nipah
• In 2001, outbreak of human disease in Bangladesh
• Raw date palm sap contaminated with infectious bat
excretions
• Bat eaten fruits.

28. Nipah Encephalitis:contd…
• After exposure and an incubation period of 5 to 14 days,
illness presents with fever and headache, followed by
drowsiness, disorientation and mental confusion
progress to coma within 24-48 hour
• PCR from throat and nasal swabs, cerebrospinal fluid,
urine, and blood
• Antibody detection by ELISA (IgG and IgM) can be
used

29. Nipah Encephalitis:contd…
• Supportive care.
• Proper barrier nursing techniques are important in
preventing hospital-acquired infections
• The drug Ribavirin has been shown to be effective

30. Viral Cerebellitis
• Chickenpox, childhood exanthems (measles, pertussis,
and scarlet fever), enteroviruses (mainly Coxsackie
virus), EBV, Mycoplasma, CMV, HSV
• Acute gait & limb ataxia having bilateral cerebellar
features
• MRI is normal in the majority some show
enhancement of cerebellar cortical ribbon
• Slow recovery, but permanent residua may follow.

31. Investigations
• Hb%, TC,DC,ESR,PBF,Blood Culture
• S. electrolytes, S. creatinine, Urine R/E
• RBS,LFT, CXR P/A View, MT
• Serum viral Antibody & PCR
• MRI of brain with contrast
• CSF study: ADA, Antibody, PCR, virus isolation
• EEG

32. Investigations:contd…
CSF Study:
• The characteristic CSF profile is lymphocytic
pleocytosis, a mildly elevated protein concentration, and
a normal glucose concentration.
• Cell counts exceed 500/μL,certain arboviruses, mumps
and LCMV may occasionally result in cell counts
>1000/μL
• Polymorphonuclear pleocytosis WNV encephalitis
and CMV myeloradiculitis

33. Investigations:contd…
• A significant number of red blood cells (>500/μL) in the
CSF in hemorrhagic encephalitis seen with HSV
• A decreased CSF glucose unusual in viral encephalitis
and should suggest the possibility of bacterial, fungal,
tuberculous, parasitic, leptospiral, syphilitic, sarcoid, or
neoplastic meningitis.
• Rare patients with mumps, LCMV, or advanced HSV
encephalitis and many patients with CMV
myeloradiculitis have low CSF glucose concentrations.

34. Investigations:contd…
CSF PCR:
• CSF PCR has become the primary diagnostic test for
CNS infections caused by HSV, CMV, EBV, HHV-6, and
enteroviruses
• The sensitivity (∼96%) and specificity (∼99%) of HSV
CSF PCR
• Enteroviral CSF PCR appears to have a sensitivity and
specificity of >95%. The specificity of EBV CSF PCR has
not been established

35. Investigations:contd…
• May initially negative HSV CSF PCR obtained early
(≤72 h) following symptom onset and that became
positive when repeated 1–3 days later.
• The frequency of positive HSV CSF PCRs decreases
with duration of illness, with only ∼20% of cases
remaining positive after ≥14 days.
• PCR results are generally not affected by ≤1 week of
antiviral therapy

36. Investigations:contd…
Serological Study & Antigen Detection:
• In patients with HSV encephalitis, both antibodies &
antigens have been detected in the CSF & serum
• Optimal detection of both HSV antibodies and antigen
typically occurs after the first week of illness, limiting
the utility of these tests in acute diagnosis
• Nonetheless, HSV CSF antibody testing is of value in
selected patients whose illness is >1 week in duration
and who are CSF PCR–negative for HSV

37. Investigations:contd…
Neuroimaging:
• These tests help identify or exclude alternative
diagnoses and assist in the differentiation between a
focal (HSV), as opposed to a diffuse, encephalitic
process
• In HSV encephalitis orbitofrontal, anterior, and
medial temporal lobes in the 90% cases
• WNV: deep brain structures, including the thalamus,
basal ganglia, and brainstem

38. Investigations:contd…
• VZV encephalitis may show multifocal areas of
hemorrhagic and ischemic infarction
• CMV often have enlarged ventricles with areas of
increased T2 signal on MRI outlining the ventricles
• L. monocytogenes may have brainstem leision
• Nipahvirus causes diffuse MRI changes

39. Herpes Simplex Encephalitis-Neuroimaging
• Typically, T2 wieghted MRI reveals hyperintensity corresponding to edematous
changes in the temporal lobes, inferior frontal lobes, and insula, with a
predilection for the medial temporal lobes. Foci of hemorrhage occasionally
can be observed on MRI.
T2 weighted image in a 62-year-old woman
with confusion and herpes encephalitis shows
T2 hyperintensity involving the right temporal
lobe.

40. Top Image: Axial diffusion-weighted image reveals
restricted diffusion in the left medial temporal lobe
consistent with herpes encephalitis.
Bottom Image: Coronal T2-weighted image
reveals hyperintensity in the left temporal
lobe (arrows) in a distribution similar to the
restricted diffusion abnormality seen in the
previous image. This finding is typical for
herpes encephalitis.
Herpes Simplex Encephalitis-Neuroimaging

41. Japanese encephalitis
The most consistent finding on MRI is bilateral
increased T2 signal abnormality in the thalami
with or without hemorrhage.

42. Japanese encephalitis. Axial fluid attenuated inversion recovery images in two
different patients with Japanese encephalitis demonstrate bilateral symmetric
increased signal intensity (A) and asymmetric right thalamus signal abnormality B)
respectively.
Japanese encephalitis

43. Nipah virus encephalitis
 MRI shows fairly
characteristic findings
with small T2
hyperintense white or
grey matter lesions with
transient T1
hyperintense punctate
cortical lesions in
subacute phase
infection of brain and its linings43

44. EEG:
• HSV encephalitis have a distinctive EEG pattern
consisting of periodic, stereotyped, sharp and slow
complexes originating in one or both temporal lobe
• EEG in patients with WNV encephalitis typically show
generalized slowing that may be more anteriorly
prominent

45. HSV

46. Brain Biopsy:
Reserved for patients in:
• whom CSF PCR studies fail to lead to a specific
diagnosis,
• who have focal abnormalities on MRI, and
• who continue to show progressive clinical deterioration
despite treatment with acyclovir and supportive therapy.

47. Treatment
• In the initial stages of viral encephalitis many
patients will require care in a ICU
• Basic management include
 Careful monitoring of ICP
 Fluid restriction, avoidance of hypotonic IV
solutions
 Supression of fever
 Prophylactic anti convulsive therapy

48. Treatment:cont…
• Acyclovir is of benefit in the treatment of HSV
and should be started empirically in patients
with suspected viral encephalitis, especially if
focal features are present, while awaiting viral
diagnostic studies
• Adults should receive a dose of 10 mg/kg of
acyclovir intravenously every 8 h (30 mg/kg per
day total dose) for 14-21 days

49. Sequelae
• Cognitive impairment
• Weakness (Hemiparesis, quadriparesis)
• Hyper- or hypokinetic movement disorders,
tremor, myoclonus, and parkinsonism
• Seizure disorder
• Personality change
• Behavioral abnormality
• Cranial nerve palsy

50. Prognosis
• Directly related to the age of the patient and the level
of consciousness at the time of initiation of therapy.
• Patients with severe neurologic impairment (Glasgow
coma score 6) at initiation of therapy either died or
survived with severe sequelae.
• Young patients (<30 years) with good neurologic function
at initiation of therapy did substantially better (100%
survival, 62% with no or mild sequelae) compared with
their older counterparts (>30 years; 64% survival, 57%
no or mild sequelae)

51. Auto immune Encephalitis

52. Anti NMDA Encephalitis
• Paraneoplastic encephalitis present with an acute or sub
acute psychiatric syndrome, seizure, memory disturbance
• Associated with antibodies against a component of the
NMDA receptor
• CSF: lymphocytic pleocytosis, majority had oligoclonal
bands
• MRI showed abnormal T2 hyperintensity in medial
temporal lobes
• Resection of tumor, IVIG

53. Subacute / Chronic
Encephalitis

54. Subacute sclerosing panencephalitis
• Result of chronic measles virus infection
• Children and adolescents are affected
• Typically there is a history of primary measles
infection at a very early age followed by a 6- to 8
years asymptomatic period
• Initially decline in proficiency at school, changes
in personality, difficulty with language
• progressive intellectual deterioration with focal
or generalized seizures, myoclonus, ataxia
• As the disease advances, rigidity, hyperactive
reflexes, Babinski signs, final stage- decorticated.

55. Subacute sclerosing panencephalitis:contd…
• CSF: Protein, anti measles Antibody, Oligoclonal band
• EEG: periodic (every 5 to 8 s) bursts of 2 to 3 / s high
voltage waves
• MRI changes the subcortical white matter and
periventricular region
• No effective treatment, amantadine and inosine
pranobex, alpha interferon prolong survival
• Usually steadily progressive, death occurring within 1
to 3 years

56. Sclerosing panencephalitis (SSPE). Axial T2-weighted image
demonstrates symmetric regions of increased signal intensity
in the subcortical white matter, predominantly in the
posterior cerebrum. Serology titers and electroencephalogram
findings were compatible with SSPE.

57. Progressive Rubella Panencephalitis
• Associated with congenital rubella infection of brain
• Progressive neurologic deterioration occurred after a
stable period of 8 to 19 years
• Similar to SSPE ,progressive deterioration in behavior
and school performance, often associated with
seizures, a impairment of mental function
• CSF: Rubella specific oligoclonal bands
• No specific therapy

58. Progressive Multifocal Leukoencephalopathy
• Caused by viral infection of the CNS in patients with
impaired immunologic responses(HIV-80%)
• Characterized by widespread demyelinating lesions, mainly
cerebral hemispheres but sometimes in brainstem and
cerebellum
• Personality changes, intellectual impairment, dementia,
focal deficit, ataxia evolves over days to weeks
• Diagnosis: MRI, Virus isolation in CSF
• Treatment: anti retroviral, steroid

59.  This is an MRI of the brain of a PML survivor (PML-S). On the
left is a fluid attenuated inverse recovery (FLAIR) image,
which shows a large hyperintense lesion in the left cerebral
hemisphere, sparing the cortex. On the right is the
corresponding T1 with gadolinium (contrast) image, which
shows no enhancement within the PML lesion.

60. THANK YOU