Encephalitis Introduction

    • Definition:
      • Inflammation of brain parenchyma + neurologic dysfunction
      • Meninges are frequently involved ("encephalitis" and "meningoencephalitis" used interchangeably). 
    • Most common causes in US:  ( >100 different agents)
      • Herpes Simplex Virus Type I
        • Reactivation of latent virus in 2/3 of cases.
        • Clinically: fever, temporal lobe seizures.
        • Diagnose with CSF polymerase, treat with acyclovir.
      • West Nile Virus
        • Mosquito-borne infection worldwide.  
        • Cases in US started 1999, peaked in 2003, then variable (up and down).
        • Clinically: Acute flaccid paralysis, encephalitis, myoclonus. 
        • Dx: IgM of CSF for West Nile Virus.
      • 50% cause not identified despite many investigations. 
      • Other Types:
        • Eastern Equine Encephalitis, HHV 6, JC virus, PML, rabbies, St. Lous encephalitis virus.
    • Another approach to causes: 
      • Arthropod-borne
        • Mosquitoes
          • Arboviruses (alphavirus, flavivirus, bunyavirus)
          • West Nile
            • Crows susceptible - finding dead crows = investigation.
            • ***Mosquito protection*** is #1
      • Person-to-Person
        • MUMPs
        • Measles
        • Varicella
        • HHV-6
        • HSV1 (not HSV2)
        • Other Rare (EBV, Enterovirus, CMV)
      • Animal-to-Person
      • Rabies (bats and animals) 
    • Rarely: bacteria, protozoa, helminths
    • Herpes Simplex Encephalitis
      • Acute, necrotizing, asymmetrical hemorrhagic process with lymphocytic and plasma cell reaction (medial temporal and inferior frontal lobes). 
      • Often HSV1, but can be HSV2.
    • Symptoms:
      • Defined as:
        • Altered Mental Status lasting >24hrs.  (memory, confusion, agression, hallucinations --> temporal lobe effects) 
        • Decreased LOC (can be anywhere from mild confusion to coma).
        • Seizures (up to 40% of patients)
        • Other Symptoms:
          • Hallucinations
          • Ataxia
          • Cranial Neuropathies
          • Focal neurologic findings (if focal neuro area involved).
          • Meningeal involvement (meningoencephalitis):
          • hemicranial headache, nuchal rigidity.
          • Cerebral cortex: hallucinations, peculiar motor functions (placing underwear over pants)
      • Clinically cannot tell between viruses.  They all present the same, except rabies:
        • brainstem involvement, nucleus ambuguus, and medulla, resulting in:
          • Pt's get "hydrophobia", attemping to swallow = paryngeal spasms. 
          • Rapid, short respirations
          • Hyperactivity/autonomic dysfunction, rarely ascending paralysis.
    • Investigations:
      • Standard of care for encephalitis includes:
        • 1.  LP
        • 2.  MRI
        • 3.  EEG
      • LP for CSF
        • Lymphocytic pleocytosis, but CSF can be acellular.
        • LP be normal in 5-10% of patients in viral encephalitis
        • Test CSF for PCR HSV1 + other organisms based on edidemiologically relevant (seasons, geography, exposures, rash, etc..)
          • West Nile IgM
      • MRI is needed to detect encephalitis (more sensitive than CT)
        • Can also do CT and EEG based on sx.
    • See specific causes of encephalitis below for more specific signs/symptoms/treatment.


    HSV1 Encephalitis

    • Most common in US, mostly affects young and elderly patients.
    • Organism:
      • HSV1 >90%, and HSV2 10%.
      • More than 2/3 due to re-activation of latent HSV1 rather than primary infection.
    • Mortality rate 15-30%, and those that survive commonly have neuropsychiatric sequelae.
    • Symptoms:
      • mostly headache, fever, mental status change (present within a week).
        • <10% of pts have oral/labial herpetic lesions. 
        • Partial complex seizures can occur (involves temporal lobes). 
      • If not recognized, progress to bilateral temporal lobe hemorrhagic necrosis --> severe
    • Labs:
      • LP demonstrates lymphocytic pleocytosis, but normal in ~5%
      • Diagnosis:
        • PCR HSV (Sn >95%, Sp ~100%), --> diagnostic!
        • PCR can be negative early in infection.  IF PCR negative, but suspect encephalitis treat anyway and repeat LP 3-7d later. (should remain positive >7 days).
        • NOTE: viral cultures insensitive, and serologic studies are non-specific.
          • Can biopsy in extreme cases.
          • Presence of RBC in CSF without trauma can suggest HSV.
    • EEG: Periodic latererlizing epileptiform discharges (PLEDs), localize to temporal lobes.
    • Neuroimaging: Localize lesions to one or both temporal lobes.
    • Treatment:
      • IV acyclovir (begin empiric IV acyclovir before PCR results).
        • If PCR positive, continue IV acyclovir for 14-21 days.
        • NOTE: Oral antivirals (i.e. valacyclovir) have poor CSF penetration, MUST use IV acyclovir. 
        • Can discontinue if negative PCR and suspision becomes low.

    West Nile Virus

    • First detected in 1999.
    • Spread by bite of a mosquito, peak in late summer and early fall.
    • Symptoms (3 possibilities)
    1. Asymptomatic (80%)
    2. Symptomatic fever (20%)
      • Feverfatiguerash, headache, anorexia, back pain, myalgia.
    3. Neuroinvasive disease (<1%)
      • Typically adults > 50y affected.
      • Meningitisencephalitismyelitis (often overlapping).
      • Objective finding of Focal Weakness - IMPORTANT CLUE, characteristic.
        • Manifests as an acute flaccid paralysis, can even involve diaphragm (similar to polio).
      • Extrapyramidal signs: tremors, bradykinesia (as in Parkinsons).
      • Rash (possible, but uncommon in neuroinvasive.  Typically sign of symptomatic fever group).
    • Labs:
      • Lumbar Puncture:
        • Lymphocyte dominant pleocytosis, but more neutrophils than other viral CNS infections. 
        • Send CSF for West Nile Virus IgM = diagnostic
          • Reliably detected within 9 days of onset of fever, and persists for >1yr.
          • Some cross-reaction to other flavi-viruses (st. louis encephalitis, Japanese encephalitis, dengue, yellow fever - false positives.
          • PCR gives false negatives, likely because brief period of viremia in WNV.
      • MRI:
        • Bilateral enhancement of thalamus and basal ganglia on T2 MRI images.
    • Treatment
      • Supportive
      • Evaluating roles of aminotherapy, some unpublished studies with IVIG.
      • Prevention is most important by mosquity protection. 




    • Wash bite wound with 20% soap
    • irrigate with virucidal agent (i.e. povidone iodine).
    • Inject Rabies Ig (20 IU/kg) around the wound (via IM)
    • Rabies vaccine: on days 0, 3, 7, 14, 28


    Non-Infectious Encephalitis

    • Anti-NMDA Receptor Encephalitis

      • Paraneoplastic Syndrome
        • Often associated with ovarian teratomas
      • Symptoms:
        • Usually a prodomal flu-like syndrome
        • Followed by:
          • Memory Disturbance
          • Personality Change
          • Psychosis
          • Encephalopathy
          • Seizures
          • Oral Dyskinesia (involuntary mouth movements)
      • Findings:
        • Usually MRI FLAIR - shows signal in temporal lobes.
        • CSF can be normal, but usually mild lymphocytic pleocytosis with mild elevated protein.
      • Diagnosis:
        • Finding Anti-NMDA receptor antibodies in CSF or serum
      • Treatment:
        • Treat Teratoma (i.e. Oophorectomy)
        • Cover for HSV encephalitis until cause known.
    • Anti-Hu (Anti-ANNA-1)

      • Paraneoplastic Syndrome (autoantibody)
        • Usually older patients
        • Associated with: Small Cell Lung Ca
      • Symptoms (MOTOR or SENSORY)



    • HSV1: 50-60% mortality
    • Rabies mortality: 100%
    • Eastern equin encephalitis 70%
    • West Nile - > often mild and subclinical disease (worse in elderly --> flaccid paralysis).
    • Venezuelan equine encephalitis --> mild
    • Japanese encephalitis --> varies



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