Encephalitis

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Encephalitis

• Atman Shah

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Encephalitis

• Definition
• Inflammation of the brains meninges which also
  can include the parenchyma and/or spinal cord or
  nerve roots.

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Encephalitis

• In the United States 20,000 reported cases of
  encephalitis.
• Herpes virus encephalitis is MC in the US.
• Japanese virus encephalitis is the most common
  viral encephalitis outside the United States.

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Encephalitis

• Untreated Herpes encephalitis has a mortality
  rate of 50-75
• Affects males and female equally.
• Individuals at the extremes of age are at highest
  risk, particularly for herpes simplex
  encephalitis.

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Etiology

• MC causes in immunocompetent adults is HSV-1, VZV
  and enteroviruses.
• Epidemics of encephalitis are caused by
  Arboviruses

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Etiology

• Arboviruses?
• Alphaviruses Eastern Western equine
  encephalitis virus
• Flaviviruses St. Louis enceph. Virus, WNV
• Bunyaviruses California enceph. Virus serotypes

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Etiology

• Causes in immunocompromised (from organ
  transplantation, AIDS) include?
• HSV-1
• Varicella-zoster virus (VZV)
• Epstein-Barr virus (EBV)
• cytomegalovirus (CMV)
• human herpesvirus-6 (HHV-6)
• Enteroviruses

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Clinical Presentation

• Any degree of altered consciousness, ranging from
  mild lethargy to deep coma.
• Personality changes, hallucinations, agitations
  and other behavior disorders.
• Focal or generalization seizures may occur.
• Neurological disturbances

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Clinical Presentation (cont.)

• MC focal findings include
• (depending on location of inflammation)
• aphasia ataxia
• hemiparesis,
• DTR, Babinski reflex ve,
• myoclonic jerks other movement disorders
• tremors and cranial nerve deficits.

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Clinical Presentation (cont.)

• Hypothalamic-Pituitary axis (HPA) may be involved
  resulting in?
• Temperature dysregulation
• SIADH

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Pathophysiology (1)

• Primary infection with HSV-1 usually occurs in
  the oropharyngeal mucosa and is typically
  asymptomatic.
• Symptomatic disease is characterized by fever,
  pain, and an inability to swallow caused by
  lesions on the buccal and the gingival mucosa.
  The duration of illness is 2 to 3 weeks.

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Pathophysiology (2)

• After primary infection, HSV-1 is spread by
  retrograde transport via a division of the
  trigeminal nerve
• The virus then establishes latency in the
  trigeminal ganglion. Reactivation of latent
  ganglionic infection with replication of virus
  leads to viral encephalitis

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Pathophysiology (3)

• HSV-1 encephalitis may also be the result of
  primary infection from either intranasal
  inoculation of virus with direct invasion of the
  olfactory bulb and tract leading to ? infection
  in the temporal cortex and limbic system
  structures.

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HSV-1 encephalitis showing extensive destruction
of inferior frontal and anterior temporal lobes.
(seizures, personality change, and neurologic
deficits)
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Histopathology

• Necrotizing inflammatory process characterizes
  the acute herpes encephalitis
• Perivascular inflammatory infiltrates are usually
  present, and Cowdry type A intranuclear viral
  inclusion bodies may be found in both neurons and
  glia.

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Necrotizing inflammatory process characterizes
the acute herpes encephalitis
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Differential Diagnosis

• Brain Abscess
• Epidural and Subdural Infections
• Neoplasms
• Meningitis
• Stroke (Hemorrhagic or Ischemic)

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Diagnosis

• Cerebrospinal fluid analysis
• CSF analysis typically reveals a mononuclear
  pleocytosis (5-500 cells/mm) with mildly
  elevated protein and normal or mildly reduced
  glucose
• Because of the hemorrhagic nature of the process
  within the brain parenchyma, the red blood cell
  (RBC) count is usually elevated.

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Diagnosis

• Polymerase chain reaction
• PCR analysis of CSF is sensitive and specific for
  the diagnosis of HSE, even in patients already
  taking antiviral therapy. (has replaced brain
  biopsy as the criterion standard for establishing
  the diagnosis)
• Results are usually available within 24 hours of
  receipt of the CSF specimen.

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Diagnosis

• Imaging Studies Magnetic resonance imaging
• MRI of the brain is the preferred imaging study.
• The MRI shows pathologic changes, which are
  usually bilateral, in the medial temporal and
  inferior frontal areas.
• Findings of localized temporal abnormalities are
  highly suggestive of HSE, but confirmation of the
  diagnosis depends on identification of HSV by
  means of PCR or brain biopsy.

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Treatment

• The DOC for HSE is acyclovir, an antiviral agent
  that selectively inhibits viral replication.
  Intravenous acyclovir (10 mg/kg every 8 hours for
  2-3 weeks) is standard
• Acyclovir has relatively few serious adverse
  effects. The drug is excreted by the kidney, and
  the dose should be reduced in patients with renal
  dysfunction.
• Acyclovir is considered to be appropriate for
  serious infections during pregnancy.

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Case Presentation

• 65 year old man who presented with a seizure
  after a three day h/o abdominal pain, odd smells,
  and low grade fever.
• Six weeks previously he had numbness and tingling
  of the right arm, face and leg which resolved.CT
  scan performed at that time was normal.
• On admission, the temperature was 104 degrees F.

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Case Presentation (cont.)

• Spinal fluid contained?
• 113 WBCs
• 40 RBCs
• protein 97
• glucose 80
• Unit (mg/dl)

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Case Presentation (cont.)

• He was treated with acyclovir, and multiple blood
  and CSF cultures were negative.
• On examination
• The patient was awake and alert with good
  attention.
• His language was fluent and spontaneous, though
  he perseverated and confabulated.
• Comprehension of simple verbal commands and word
  repetition were normal.
• Memory was intact to three of three objects at
  three minutes.

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Case Presentation (cont.)

• Magnetic resonance imaging was performed 5 days
  after onset of his current symptoms.

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In this set of images, there is a region of very
bright signal on MR in the medial temporal lobe
at left (patient's right).
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Case Presentation (cont.)

• Treatment Outcome
• The patient improved dramatically after a three
  week course of acylovir.
• (Intravenous acyclovir (10 mg/kg every 8 hours
  for 3 weeks)
• Impaired renal function developed, presumed due
  to acyclovir.