2. Introduction
Encephalitis is defined as an inflammation of the brain caused either
by infection, usually with a virus, or from a primary autoimmune
process .
Many patients with encephalitis also have evidence of associated
meningitis (meningoencephalitis) and, in some cases, involvement of
the spinal cord or nerve roots (encephalomyelitis,
encephalomyeloradiculitis)
3. Definitions
Meningoencephalitis - is an acute inflammatory process involving
the meninges and to a variable degree, brain tissue. Is a common
term that recognizes the overlap
Encephalopathy - describes a clinical syndrome of altered mental
status, manifesting as reduced consciousness or altered behaviour.
9. Viral encephalitis
WHO Clinical case definition of acute encephalitis syndrome
• Person of any age, at any time of year, with
• Acute onset of fever AND
• 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)
• Other early clinical findings can include an increase in irritability,
somnolence or abnormal behaviour greater than that seen with usual
febrile illness
10. herpes simplex virus type 1 (HSV1) is reportedly the commonest
cause of adult sporadic encephalitis while varicella zoster virus (VZV)
account for most of paediatric encephalitis
Recent studies have identified many emerging encephalitic viruses
such as Chandipura and Nipah viruses particularly in South Asia
11.
12.
13. Scenario in Nepal
Although Japanese encephalitis virus (JEV) was thought to be a
major cause for acute encephalitis syndrome, more non-Japanese
encephalitis virus cases are reported.
N 52 –
Encephalitis 9
JE -33%
HSV 1- 22.2%
cause not known – 44.8%(4)
19. Specific sites of viral predilection
Temporal and inferior frontal lobes (HSV)
Periventricular areas (CMV)
Limbic system (RV)
Cerebellum (VZV)
Basal ganglia (JEV)
20. Clinical manifestations
Fever
Headache
Lethargy
Vomiting
Impairment of consciousness (confusion, behavioral abnormalities,
lethargy to coma )
Focal neurological signs 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).
Seizures.
21. may have hallucinations, agitation, personality change, behavioral
disorders, and, at times, a frankly psychotic state.
Involvement of the hypothalamic-pituitary axis may result in
temperature dysregulation, diabetes insipidus, or the development
of SIADH
22. occasionally accompanied by photophobia and a stiff neck.
Physical examination characteristically reveals signs of nuchal
rigidity, but its absence does not rule out the diagnosis.
23. Clinical clues
Encephalitis associated with GIT symptoms
-Enteroviruses,
-Rotavirus,
- Parechovirus.
Encephalitis associated with respiratory illness
-Influenza viruses: Myositis may also be associated.
-Paramyxoviruses,
- Bacteria.
27. CSF examination
CSF pleocytosis ( >5 cells/μL) - 95% patients
rare cases, a pleocytosis may be absent on the initia lumbar
puncture (LP) but present on subsequent LPs.
Mildly elevated protein
Normal glucose concentration
CSF pressure normal or slightly raised
28. Arboviruses (e.g., EEE virus or California encephalitis virus), mumps,
and lymphocytic choriomeningitis virus (LCMV) may occasionally
cell counts >1000/μL
Atypical lymphocytes -EBV , CMV, HSV
plasmacytoid or Mollaret-like large mononuclear cells –WNV
About 20% of patients with encephalitis will have a significant
number of red blood cells (>500/μL) in the CSF in a nontraumatic tap.
hemorrhagic encephalitis of the type seen with HSV
29. CSF PCR
primary diagnostic test for CNS infections caused by CMV, EBV, HHV-6,
and enteroviruses.
sensitivity (~96%) and specificity (~99%) of HSV CSF PCR
negative HSV CSF PCR tests that were obtained early (≤72 h) following
symptom onset and that became positive when repeated 1–3 days
later.
PCR results are generally not affected by ≤1 week of antiviral therapy
30. CSF culture is generally of limited utility in the diagnosis of acute
viral encephalitis.
Serum antibody determination is less useful for viruses with high
seroprevalence rates in the general population such as HSV,VZV,
CMV, and EBV
antibodies to HSV-1 glycoproteins and HSV glycoprotein antigens
have been detected in the CSF. 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.
Useful in detecting illness is >1 week in duration and who are CSF
PCR–negative for HSV .
31. EEG
EEG is strongly recommended in any suspected case of acute
encephalitis since it may help in distinguishing focal encephalitis
from generalised encephalopathy.
non-specific (slowing) with more characteristic changes (2–3 Hz
periodic lateralised epileptiform discharges originating from the
temporal lobes) limited to about half the cases in the later stages
32. Imaging
CT
subtle low density within the anterior and medial parts of the
temporal lobe and the island of Reil (insular cortex)
MRI
33. Temporal lobe involvement is strongly suggestive of herpes simplex
virus (HSV) encephalitis, although other herpes viruses (eg,VZV,
Epstein-Barr virus, human herpesvirus 6)
areas of increased signal intensity in the frontotemporal, cingulate,
or insular regions of the brain on T2 ,(FLAIR), or dwi MRI common in
HSV encephalitis.
thalamus or basal ganglia may be observed in the setting of
encephalitis due to respiratory viral infection, Creutzfeld-Jacob
disease, arbovirus, and tuberculosis
38. Management
Emergent issues
-ABC of resuscitation
-Consider admission to ICU
-Fluid restriction
-Avoidance of hypotonic intravenous solutions
-Suppression of fever
-Management of raised ICP
39. Acyclovir is of benefit in the treatment of HSV and should be
started empirically in patients with suspected viral encephalitis .
deoxypyrimidine (thymidine) kinase
acyclovir acyclovir-5′-monophosphate
inhibiting viral DNA polymerase and by causing premature
termination of nascent viral DNA chains
40. IV Acyclovir 10mg/kg every 8 hrly ( 30mg/kg total daily dose)
* 21 days
acyclovir should be diluted to a concentration ≤7 mg/mL , Each dose
should be infused slowly over 1 h minimize the risk of renal
dysfunction .
Oral antiviral drugs with efficacy against HSV,VZV, and EBV,
including acyclovir, famciclovir, and valacyclovir, have not been
evaluated
41. IV Dexamethasone (10 mg every 6 h intravenously for 4 days) is
efficacious .
Ganciclovir and foscarnet, either alone or in combination, are
often used in the treatment of CMV-related CNS infection.
-Induction Ganciclovir 5 mg/kg every 12 h given IV over 1 h. -
maintenance therapy of 5 mg/kg every day for an indefinite period
-induction Foscarnet 60 mg/kg every 8 h administered by constant
infusion over 1 h. For 14-21 days
maintenance therapy (60–120 mg/kg per day) cont.
42. Intravenous ribavirin (15–25 mg/kg per day in divided doses given every
8 h) California encephalitis (LaCrosse) virus.
No specific antiviral therapy of proven efficacy is currently available for
treatment of WNV encephalitis
Patients have been treated with interferon-α, ribavirin, an Israeli IVIg
preparation that contains high-titer anti-WNV antibody (Omr-IgG-am)
43. Seizures should be treated with standard anticonvulsant regimens,
and prophylactic therapy should be considered in view of the high
frequency of seizures in severe cases of encephalitis
44. Features of raised ICP
Asymmetric pupil,
Tonic posturing,
Papilloedema
Managemant
- Proper positioning: Head elevated 15-300.
-Fluid Restriction: 2/3rd of maintenance.
• 20% Mannitol 5 ml/kg over 10 – 15 min followed by 3
ml/kg every 6 hourly for 48 hrs then SOS, or
-Acetazolamide: 50 – 75 mg/kg/day, or
-Glycerin: 1 ml/kg/day through NGTube
45.
46.
47. Japanese encephalitis
JEV is the most important cause of viral encephalitis in Asia.
Primarily affects children under age 15 .
Most JEV infections are mild (fever and headache) or without
apparent symptoms
transmitted to humans through bites from infected mosquitoes of
the Culex species
WHO recommends testing for JEV-specific IgM antibody in a single
sample of cerebrospinal fluid (CSF)
There is no antiviral treatment for patients with JE
48. Nipah virus encephalitis
first recognised among pig farmers in Malaysia between 1998 and 1999
paramyxovirus (named Nipah virus)
human illness was characterised by a history of direct contact with pigs
in the livestock farm.
short incubation period (two weeks), rapidly declining level of
consciousness, prominent brain stem dysfunction, and high fatality
rates.
segmental myoclonus, areflexia, hypotonia, and dysautonomia
Supportive care is the mainstay of treatment
49. Sequele
Behavioural and psychiatric disturbances
Epilepsy
Post-encephalitic parkinsonism
Memory difficulties
Speech disturbances
Permanent home care
50. Prognosis
Factors of bad prognosis
• Severe neurologic impairment
• Older age
• High viral load in CSF
• Delay in initiation of therapy
52. Take home message
-Acute viral encephalitis is frequently devastating-
-All patients with a febrile illness and altered behaviour or
consciousness should be investigated promptly for viral
encephalitis
-Patients suspected need a lumbar puncture as soon as
possible
-Early institution of therapy improves prognosis