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Acute Viral
Encephalitis/
Meningitis
Dr. Shatdal Chaudhary, M.D.
Associate Professor
Universal College of Medical Sciences,
Bhairahawa, Nepal
Email: shatdalchaudhary@yahoo.com
Introduction
• Encephalitis is an acute inflammatory process affecting the brain
parenchyma
• Meningoencephalitis
• Encephalomyelitis
• Encephalomyeloradiculitis

• Viral infection is the most common and important cause, with
over 100 viruses implicated worldwide
• Incidence of 3.5-7.4 per 100,000 persons per year
• ~20,000 cases reported anually in USA
Causes of Viral Encephalitis
• Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, EpsteinBarr virus, human herpes virus 6
• Adenoviruses
• Influenza A
• Enteroviruses, poliovirus
• Measles, mumps, and rubella viruses
• Rabies
• Arboviruses – examples: Japanese encephalitis; St. Louis encephalitis virus;
West Nile encephalitis virus; Eastern, Western and Venzuelan equine
encephalitis virus; tick borne encephalitis virus
• Bunyaviruses – examples: La Crosse strain of California virus
• Reoviruses – example: Colorado tick fever virus
• Arenaviruses – example: lymphocytic choriomeningitis virus
What Is An Arbovirus?
• Arboviruses = arthropod-borne viruses
• Arboviruses are maintained in nature through biological
transmission between susceptible vertebrate hosts by bloodfeeding arthropods
• Vertebrate infection occurs when the infected arthropod
takes a blood meal
Major Arboviruses That Cause
Encephalitis
• Flaviviridae
• Japanese encephalitis
• St. Louis encephalitis
• West Nile

• Togaviridae
• Eastern equine encephalitis
• Western equine encephalitis

• Bunyaviridae
• La Crosse encephalitis
Japanese
Encephalitis
Japanese Encephalitis
• Flavivirus related to St. Louis
encephalitis
• Most important cause of
arboviral encephalitis worldwide,
with over 45,000 cases reported
annually
• Transmitted by culex mosquito,
which breeds in rice fields
• Mosquitoes become infected by
feeding on domestic pigs and wild
birds infected with Japanese
encephalitis virus. Infected
mosquitoes transmit virus to
humans and animals during the
feeding process.
History of Japanese
Encephalitis
• 1800s – recognized in Japan

• 1924 – Japan epidemic. 6125 cases, 3797 deaths
• 1935 – virus isolated in brain of Japanese patient
who died of encephalitis
• 1938 – virus isolated from Culex mosquitoes in
Japan
• Today – extremely prevalent in South East Asia.
30,000-50,000 cases reported each year.
Distribution of Japanese
Encephalitis in Asia, 1970-1998
West Nile Virus
West Nile Virus
• Flavivirus
• Primary host – wild
birds
• Principal arthropod
vector – mosquitoes
• Geographic distribution
- Africa, Middle East,
Western Asia, Europe,
Australia, North
America, Central
America
http://www.walgreens.com/images/library/healthtips/july02/westnilea.jpg
St. Louis
Encephalitis
St. Louis Encephalitis
• Flavivirus
• Most common
mosquito-transmitted
human pathogen in the
US
• Leading cause of
epidemic flaviviral
encephalitis
Eastern Equine Encephalitis
• Togavirus
• Caused by a virus transmitted to
humans and horses by the bite of
an infected mosquito.
• 200 confirmed cases in the US
1964-present
• Human cases occur relatively
infrequently, largely because the
primary transmission cycle takes
place in swamp areas where
populations tend to be limited.
Western Equine Encephalitis
• Togavirus
• Mosquito-borne
• 639 confirmed cases in
the US since 1964
• Important cause of
encephalitis in horses
and humans in North
America, mainly in the
Western parts of the US
and Canada
La Crosse Encephalitis
• Bunyavirus
• On average 75 cases per year
reported to the CDC
• Most cases occur in children under
16 years old
• Zoonotic pathogen that cycles
between the daytime biting treehole
mosquito, and vertebrate amplifier
hosts (chipmunk, tree squirrel) in
deciduous forest habitats
• 1963 – isolated in La Crosse, WI from
the brain of a child who died from
encephalitis
Summary – Confirmed and Probable
Human Cases in the US
Virus

Years

Total cases

Eastern Equine

1964-2000

182

Western Equine 1964-2000

649

La Crosse

1964-2000

2,776

St. Louis

1964-2000

4,482

West Nile

1999-present

> 9,800
Acute Viral Meningitis
• Enterovirus(coxaschie viruses, echovirus,human
enterovirus68-71
• HSV 2
• HIV
• Arbovirus
• VZV
• EBV
Clinical
Manifestations
Symptoms
• Fever

• Headache,
• Malaise, Anorexia, Nausea and Vomiting
• Abdominal pain
• Altered level of consciousness
• Mild lethargy to Coma

• Behavioral changes, hallucinations, agitations,
personality changes, frank psychosis
• Focal neurologic deficits:
• Virtually every possible focal neurological disturbance
has been reported.
• Aphasia
• Ataxia
• Weakness: Hemiparesis with hyperactive tendon
reflexes
• Cranial nerve deficits
• Involantary movements- tremors, myoclonic jerks
• Seizures >50% patients

• SIADH
Patient History
• Detailed history critical to determine the likely cause of encephalitis.
• Prodromal illness, recent vaccination, development of few days →
Acute Disseminated Encephalomyelitis (ADEM) .
• Biphasic onset: systemic illness then CNS disease → Enterovirus
encephalitis.
• Abrupt onset, rapid progression over few days → HSE.
• Recent travel and the geographical context:
• Africa → Cerebral malaria
• Asia → Japanese encephalitis
• High risk regions of Europe and USA → Lyme disease

• Recent animal bites → Tick borne encephalitis or Rabies.
• Occupation

• Forest worker, exposed to tick bites
• Medical personnel, possible exposure to infectious diseases.
Lab Investigation
• CSF examination: Should be performed in all the
patients until contraindicated
• Diagnosis is usually based on CSF
•
•
•
•
•

Mild increase in protein
Inrease cells with predominantly lymphocytes
Normal glucose
Absence of bacteria on culture.
Viruses occasionally isolated directly from CSF
• Less than half are identified
Laboratory Diagnosis
• CSF PCR techniques
• Detect specific viral DNA in CSF
• Usually available for HSVCMV, EBV, HHV6, ENTEROVIRUS, VZV

• CSF CULTURE
MRI/ CT Scan
• Can exclude subdural bleeds, tumor, and sinus
thrombosis
• Help by
• Focal or diffuse ence4phalitis process
• In HSV encephalitis- 80% abnormalities in temporal lobe
MRI
MRI
EEG
• In HSV: Periodic focal temporal lobe spikes on a background of
slow or low amplitude activity.
Brain Biopsy
• Is generally reserved for patients in whom CSF PCR fail to lead
a specific diagnosis
•

Reserved for patients who are worsening, have an undiagnosed
lesion after scan, or a poor response to acyclovir.
D/D
•
•
•
•
•
•
•
•
•
•
•
•

Tuberculosis, Fungal, Rickettsia, Mycoplasma, Bacterial
Anoxic/Ischemic conditions
Metabolic disorders
Nutritional deficiency
Toxic (Accidental & Intentional)
Systemic infections
Critical illness
Malignant hypertension
Hashimoto’s encephalopathy
Traumatic brain injury
Epileptic (non-convulsive status)
CJD (Mad Cow)
Treatment
• Suppportive
•
•
•
•
•
•
•

Vital monitoring
ABC
IVF
Treatment of raised ICP
Bed Care
Nutrition
DVT prophylaxis
Supportive Therapy
• Fever, dehydration, electrolyte imbalances, and
convulsions require treatment.
• For cerebral edema severe enough to produce
herniation, controlled hyperventilation,
mannitol, and dexamethasone.

• Patients with cerebral edema must not be overhydrated.
• If these measures are used, monitoring ICP should be considered.

• If there is evidence of ventricular enlargement,
intracranial pressure may be monitored in
conjunction with CSF drainage.
Acyclovir
• Acyclovir is a synthetic purine nucleoside analogue with
inhibitory activity against HSV-1 and HSV-2, varicella-zoster
virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus
(CMV)
• In order of decreasing effectiveness
• Acyclovir 10 mg/kg 8 hrly 14-21day
Acyclovir Action
• Thymidine Kinase (TK) of uninfected cells does not use acyclovir as a
substrate.
• TK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovir
monophosphate.
• The monophosphate is further converted into diphosphate by
cellular guanylate kinase and into triphosphate by a number of
cellular enzymes.
• Acyclovir triphosphate interferes with Herpes simplex virus DNA
polymerase and inhibits viral DNA replication.
• Acyclovir triphosphate incorporated into growing chains of DNA by
viral DNA polymerase.
• When incorporation occurs, the DNA chain is terminated.
• Acyclovir is preferentially taken up and selectively converted to the
active triphosphate form by HSV-infected cells.
• Thus, acyclovir is much less toxic in vitro for normal uninfected cells
because: 1) less is taken up; 2) less is converted to the active form.
• Ganicyclovir/Foscarnet: For CMV related CNS infection
• Ganicyclovir 5mg/kg (over 1 hr) 12 hrly during induction therapy
the od in maintenance therapy
• Foscarnet: 60mg/kg 8hrly during induction then maintenance 60120 mg/kg
Dexamethasone
• Synthetic adrenocortical steroid
• Potent anti-inflammatory effects
• Dexamethasone injection is generally administered initially via
IV then IM
• Side effects: convulsions; increased ICP after treatment;
vertigo; headache; psychic disturbances
Prognosis
• The mortality rate varies with etiology, and epidemics
due to the same virus vary in severity in different years.
• Bad: Eastern equine encephalitis virus infection, nearly 80% of
survivors have severe neurological sequelae.
• Not so Bad: EBV, California encephalitis virus, and Venezuelan
equine encephalitis virus, severe sequelae are unusual.
• Approximately 5 to 15% of children infected with LaCrosse virus
have a residual seizure disorder, and 1% have persistent
hemiparesis.

• Permanent cerebral sequelae are more likely to occur in
infants, but young children improve for a longer time
than adults with similar infections.
• Intellectual impairment, learning disabilities, hearing loss, and
other lasting sequelae have been reported in some studies.
Prognosis w/ Treatment
• Considerable variation in the incidence and severity of sequelae.
• Hard to assess effects of treatment.

• NIAID-CASG trials:

• The incidence and severity of sequelae were directly related to the age
of the patient and the level of consciousness at the time of initiation of
therapy.
• Patients with severe neurological impairment (Glasgow coma score 6) at
initiation of therapy either died or survived with severe sequelae.
• Young patients (<30 years) with good neurological 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).

• Recent studies using quantitative CSF PCR tests for HSV indicate that
clinical outcome following treatment also correlates with the
amount of HSV DNA present in CSF at the time of presentation.
Vaccination
• None for most Encephalitides
• JE
• Appears to be 91% effective
• There is no JE-specific therapy other than supportive
care
• Live-attenuated vaccine developed and tested in China
• Appears to be safe and effective
• Chinese immunization programs involving millions of children

• Vero cell-derived inactivated vaccines have been
developed in China
• 2 millions doses are produced annually in China and Japan

• Several other JE vaccines under development

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Acute Viral encephalitis Dr. Shatdal Chaudhary

  • 1. Acute Viral Encephalitis/ Meningitis Dr. Shatdal Chaudhary, M.D. Associate Professor Universal College of Medical Sciences, Bhairahawa, Nepal Email: shatdalchaudhary@yahoo.com
  • 2. Introduction • Encephalitis is an acute inflammatory process affecting the brain parenchyma • Meningoencephalitis • Encephalomyelitis • Encephalomyeloradiculitis • Viral infection is the most common and important cause, with over 100 viruses implicated worldwide • Incidence of 3.5-7.4 per 100,000 persons per year • ~20,000 cases reported anually in USA
  • 3. Causes of Viral Encephalitis • Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, EpsteinBarr virus, human herpes virus 6 • Adenoviruses • Influenza A • Enteroviruses, poliovirus • Measles, mumps, and rubella viruses • Rabies • Arboviruses – examples: Japanese encephalitis; St. Louis encephalitis virus; West Nile encephalitis virus; Eastern, Western and Venzuelan equine encephalitis virus; tick borne encephalitis virus • Bunyaviruses – examples: La Crosse strain of California virus • Reoviruses – example: Colorado tick fever virus • Arenaviruses – example: lymphocytic choriomeningitis virus
  • 4. What Is An Arbovirus? • Arboviruses = arthropod-borne viruses • Arboviruses are maintained in nature through biological transmission between susceptible vertebrate hosts by bloodfeeding arthropods • Vertebrate infection occurs when the infected arthropod takes a blood meal
  • 5. Major Arboviruses That Cause Encephalitis • Flaviviridae • Japanese encephalitis • St. Louis encephalitis • West Nile • Togaviridae • Eastern equine encephalitis • Western equine encephalitis • Bunyaviridae • La Crosse encephalitis
  • 6.
  • 8. Japanese Encephalitis • Flavivirus related to St. Louis encephalitis • Most important cause of arboviral encephalitis worldwide, with over 45,000 cases reported annually • Transmitted by culex mosquito, which breeds in rice fields • Mosquitoes become infected by feeding on domestic pigs and wild birds infected with Japanese encephalitis virus. Infected mosquitoes transmit virus to humans and animals during the feeding process.
  • 9. History of Japanese Encephalitis • 1800s – recognized in Japan • 1924 – Japan epidemic. 6125 cases, 3797 deaths • 1935 – virus isolated in brain of Japanese patient who died of encephalitis • 1938 – virus isolated from Culex mosquitoes in Japan • Today – extremely prevalent in South East Asia. 30,000-50,000 cases reported each year.
  • 12. West Nile Virus • Flavivirus • Primary host – wild birds • Principal arthropod vector – mosquitoes • Geographic distribution - Africa, Middle East, Western Asia, Europe, Australia, North America, Central America http://www.walgreens.com/images/library/healthtips/july02/westnilea.jpg
  • 14. St. Louis Encephalitis • Flavivirus • Most common mosquito-transmitted human pathogen in the US • Leading cause of epidemic flaviviral encephalitis
  • 15. Eastern Equine Encephalitis • Togavirus • Caused by a virus transmitted to humans and horses by the bite of an infected mosquito. • 200 confirmed cases in the US 1964-present • Human cases occur relatively infrequently, largely because the primary transmission cycle takes place in swamp areas where populations tend to be limited.
  • 16. Western Equine Encephalitis • Togavirus • Mosquito-borne • 639 confirmed cases in the US since 1964 • Important cause of encephalitis in horses and humans in North America, mainly in the Western parts of the US and Canada
  • 17. La Crosse Encephalitis • Bunyavirus • On average 75 cases per year reported to the CDC • Most cases occur in children under 16 years old • Zoonotic pathogen that cycles between the daytime biting treehole mosquito, and vertebrate amplifier hosts (chipmunk, tree squirrel) in deciduous forest habitats • 1963 – isolated in La Crosse, WI from the brain of a child who died from encephalitis
  • 18. Summary – Confirmed and Probable Human Cases in the US Virus Years Total cases Eastern Equine 1964-2000 182 Western Equine 1964-2000 649 La Crosse 1964-2000 2,776 St. Louis 1964-2000 4,482 West Nile 1999-present > 9,800
  • 19. Acute Viral Meningitis • Enterovirus(coxaschie viruses, echovirus,human enterovirus68-71 • HSV 2 • HIV • Arbovirus • VZV • EBV
  • 21. Symptoms • Fever • Headache, • Malaise, Anorexia, Nausea and Vomiting • Abdominal pain • Altered level of consciousness • Mild lethargy to Coma • Behavioral changes, hallucinations, agitations, personality changes, frank psychosis
  • 22. • Focal neurologic deficits: • Virtually every possible focal neurological disturbance has been reported. • Aphasia • Ataxia • Weakness: Hemiparesis with hyperactive tendon reflexes • Cranial nerve deficits • Involantary movements- tremors, myoclonic jerks • Seizures >50% patients • SIADH
  • 23. Patient History • Detailed history critical to determine the likely cause of encephalitis. • Prodromal illness, recent vaccination, development of few days → Acute Disseminated Encephalomyelitis (ADEM) . • Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis. • Abrupt onset, rapid progression over few days → HSE. • Recent travel and the geographical context: • Africa → Cerebral malaria • Asia → Japanese encephalitis • High risk regions of Europe and USA → Lyme disease • Recent animal bites → Tick borne encephalitis or Rabies. • Occupation • Forest worker, exposed to tick bites • Medical personnel, possible exposure to infectious diseases.
  • 24. Lab Investigation • CSF examination: Should be performed in all the patients until contraindicated • Diagnosis is usually based on CSF • • • • • Mild increase in protein Inrease cells with predominantly lymphocytes Normal glucose Absence of bacteria on culture. Viruses occasionally isolated directly from CSF • Less than half are identified
  • 25. Laboratory Diagnosis • CSF PCR techniques • Detect specific viral DNA in CSF • Usually available for HSVCMV, EBV, HHV6, ENTEROVIRUS, VZV • CSF CULTURE
  • 26. MRI/ CT Scan • Can exclude subdural bleeds, tumor, and sinus thrombosis • Help by • Focal or diffuse ence4phalitis process • In HSV encephalitis- 80% abnormalities in temporal lobe
  • 27. MRI
  • 28. MRI
  • 29. EEG • In HSV: Periodic focal temporal lobe spikes on a background of slow or low amplitude activity.
  • 30. Brain Biopsy • Is generally reserved for patients in whom CSF PCR fail to lead a specific diagnosis • Reserved for patients who are worsening, have an undiagnosed lesion after scan, or a poor response to acyclovir.
  • 31. D/D • • • • • • • • • • • • Tuberculosis, Fungal, Rickettsia, Mycoplasma, Bacterial Anoxic/Ischemic conditions Metabolic disorders Nutritional deficiency Toxic (Accidental & Intentional) Systemic infections Critical illness Malignant hypertension Hashimoto’s encephalopathy Traumatic brain injury Epileptic (non-convulsive status) CJD (Mad Cow)
  • 33. Supportive Therapy • Fever, dehydration, electrolyte imbalances, and convulsions require treatment. • For cerebral edema severe enough to produce herniation, controlled hyperventilation, mannitol, and dexamethasone. • Patients with cerebral edema must not be overhydrated. • If these measures are used, monitoring ICP should be considered. • If there is evidence of ventricular enlargement, intracranial pressure may be monitored in conjunction with CSF drainage.
  • 34. Acyclovir • Acyclovir is a synthetic purine nucleoside analogue with inhibitory activity against HSV-1 and HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) • In order of decreasing effectiveness • Acyclovir 10 mg/kg 8 hrly 14-21day
  • 35. Acyclovir Action • Thymidine Kinase (TK) of uninfected cells does not use acyclovir as a substrate. • TK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovir monophosphate. • The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. • Acyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inhibits viral DNA replication. • Acyclovir triphosphate incorporated into growing chains of DNA by viral DNA polymerase. • When incorporation occurs, the DNA chain is terminated. • Acyclovir is preferentially taken up and selectively converted to the active triphosphate form by HSV-infected cells. • Thus, acyclovir is much less toxic in vitro for normal uninfected cells because: 1) less is taken up; 2) less is converted to the active form.
  • 36. • Ganicyclovir/Foscarnet: For CMV related CNS infection • Ganicyclovir 5mg/kg (over 1 hr) 12 hrly during induction therapy the od in maintenance therapy • Foscarnet: 60mg/kg 8hrly during induction then maintenance 60120 mg/kg
  • 37. Dexamethasone • Synthetic adrenocortical steroid • Potent anti-inflammatory effects • Dexamethasone injection is generally administered initially via IV then IM • Side effects: convulsions; increased ICP after treatment; vertigo; headache; psychic disturbances
  • 38. Prognosis • The mortality rate varies with etiology, and epidemics due to the same virus vary in severity in different years. • Bad: Eastern equine encephalitis virus infection, nearly 80% of survivors have severe neurological sequelae. • Not so Bad: EBV, California encephalitis virus, and Venezuelan equine encephalitis virus, severe sequelae are unusual. • Approximately 5 to 15% of children infected with LaCrosse virus have a residual seizure disorder, and 1% have persistent hemiparesis. • Permanent cerebral sequelae are more likely to occur in infants, but young children improve for a longer time than adults with similar infections. • Intellectual impairment, learning disabilities, hearing loss, and other lasting sequelae have been reported in some studies.
  • 39. Prognosis w/ Treatment • Considerable variation in the incidence and severity of sequelae. • Hard to assess effects of treatment. • NIAID-CASG trials: • The incidence and severity of sequelae were directly related to the age of the patient and the level of consciousness at the time of initiation of therapy. • Patients with severe neurological impairment (Glasgow coma score 6) at initiation of therapy either died or survived with severe sequelae. • Young patients (<30 years) with good neurological 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). • Recent studies using quantitative CSF PCR tests for HSV indicate that clinical outcome following treatment also correlates with the amount of HSV DNA present in CSF at the time of presentation.
  • 40. Vaccination • None for most Encephalitides • JE • Appears to be 91% effective • There is no JE-specific therapy other than supportive care • Live-attenuated vaccine developed and tested in China • Appears to be safe and effective • Chinese immunization programs involving millions of children • Vero cell-derived inactivated vaccines have been developed in China • 2 millions doses are produced annually in China and Japan • Several other JE vaccines under development