Acute Viral Central Nervous System Diseases

Donald H. Gilden, M.D.
University of Colorado Health Sciences Center

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Viral Aseptic Meningitis

Viral Encephalitis

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Differential Diagnosis


Herpes Simplex Virus Type 1




Herpes Simplex Virus Type 2

Varicella-Zoster Virus

Localized Herpes Zoster (HZ)

Postherpetic Neuralgia


Arthropod-Borne Encephalitis Viruses

  • RNA viruses
  • Infection occurs primarily in summer and fall
  • Transmission from infected horses, birds, or rodents via bites from mosquitoes or ticks
  • Headache, photophobia, myalgia, fever, lethargy, confusion, seizures
  • Tremor, focal deficit may develop

St. Louis Encephalitis

  • Aseptic meningitis in 15%
  • Usually self-limited; mortality 3%–4%

Western Equine Encephalitis

  • Mortality ~ 10%
  • More severe in infants and children
  • May produce transient parkinsonism

Eastern Equine Encephalitis

  • Mortality > 50%
  • Mental, visual, auditory, speech, motor deficits in 80% of survivors

West Nile Virus Encephalitis

  • Most human cases acquired by bites from infected mosquitoes
  • Infected blood products or transplanted organs may transmit infection
  • Wide range of possible presentations
    • Meningoencephalitis
    • Rhombencephalitis
    • Opsoclonus-myoclonus cerebellar ataxia
    • Unilateral brachial plexopathy with meningoencephalitis
    • Guillain-Barré syndrome
  • MRI often shows deep-seated lesions in the basal ganglia and thalamus
  • Polymerase chain reaction (PCR) of CSF often reveals West Nile virus RNA

LaCrosse Virus Encephalitis (California Virus Encephalitis Subset)

  • Affects primarily school-age children
  • Disease usually mild
  • Seizures in 50%
  • Focal deficits, focal EEG abnormalities in 20%–40%
  • Hyponatremia common

Colorado Tick Fever

  • Transmitted in mountainous areas of western U.S. and Canada
  • Meningitis or encephalitis in 5%–10% of children


Congenital CMV

  • Most infections asymptomatic
  • Sensorineural hearing loss, intellectual deficits in some
  • Microcephaly, seizures, hypotonia, spasticity also seen

Adult Disease

  • Guillain-Barré syndrome most common neurologic complication in immunocompetent adults
  • Immunocompromised patients
    • Transplant recipients
      • Encephalitis
    • AIDS patients
      • Most common opportunistic infection in nervous system
      • Retinitis, encephalitis, progressive myelitis, polyradiculitis
      • Encephalitis
        • Subacute
        • Headache, seizures, progressive dementia, diffuse weakness
        • MRI: enhancement in ventricular ependyma (may also suggest ventriculitis)
        • CSF: neutrophilic or mononuclear pleocytosis; elevated protein; decreased glucose
        • Polyradiculitis
        • Cauda equina syndrome
          • Insidious onset
          • Asymmetrical paresthesias, distal weakness
          • Incontinence
          • Sacral-distribution sensory loss


  • Aseptic meningitis
    • Affects 5%–10% of patients early in infection
    • Headache, fever, altered mental status, focal or generalized seizures
  • Subacute encephalitis


    • Meningitis
      • Up to 23% of patients with mumps affected; encephalitis rare
      • Fatality rare
      • May be followed by aqueductal stenosis and hydrocephalus
      • Associated with typical parotitis, pancreatitis, or oophoritis


    • Encephalitis
      • Seizures and mental status changes common

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    Best Tests


    • Glucose
    • Cells
    • Gram stain
    • PCR to detect viral RNA or DNA
    • Viral culture
    • Antigen or antibody testing
    • Serologic testing (e.g., enzyme immunoassay, Western blot)


    • CT
    • MRI

      Best Therapy

      Nonspecific Therapy

      • Bed rest
      • Analgesia (headache)
      • Anticonvulsant therapy
      • Respiratory support
      • Nutritional support
      • Fluid restriction (encephalitis)
      • Monitoring for secondary infections
      • Physical therapy

        Drug Therapy

          Antiviral Agents

          • Acyclovir
            • HSV-1 encephalitis
            • HSV-2 encephalitis
            • VZV multifocal and unifocal vasculopathy
            • Dose: 15–30 mg/kg/day I.V. in three divided doses × ≥ 10 days
          • Famciclovir or valacyclovir
            • Maintenance therapy after acyclovir in AIDS patients with HSV encephalitis or VZV vasculopathy
            • Dose: famciclovir, 500 mg t.i.d., or valacyclovir, 1 g b.i.d.
          • Ganciclovir
            • CMV encephalitis
            • Dose: 5 mg/kg every 12 hr I.V. × 2 wk initially; 5 mg/kg I.V. q.d. maintenance (or 1,000 mg p.o., t.i.d., with food or 500 mg p.o., 6×/day with food)
            • Cost/mo (oral maintenance): $1,478
            • Discontinue if WBCs < 750/mm3)
          • Foscarnet
            • CMV
            • Dose: I.V. infusion, 90 mg/kg q. 12 hr or 60 mg/kg q. 8 hr over 2–3 wk
              • Adjust dose for renal impairment

          Preventive Therapy for Arthropod-Borne Viral Encephalitis

          • Routine use of insect repellents
          • Protective clothing while outdoors

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              Best References

              Gilden DH: J Neurol Sci 195:99, 2002 [PMID 11897238]

              Nash D, et al: N Engl J Med 344:1807, 2001 [PMID 11407341]

              Tedder DG, et al: Ann Intern Med 121:334, 1994 [PMID 8042822]

              Wainwright MS, et al: Ann Neurol 50:612, 2001 [PMID 11706967]

              The author has no commercial relationships with manufacturers of products or providers of services discussed in this module.

              April 2006

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