VZV encephalitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

Synonyms and keywords: Varicella zoster virus encephalitis; Herpes zoster encephalitis; Varicella zoster encephalitis; Varicella encephalitis;

Overview

VZV encephalitis is a viral infection of the central nervous system. Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic. The exact pathogenesis of VZV encephalitis is not fully understood. The immune system eliminates the virus from most locations upon initial infection, but it remains latent in the dorsal root ganglion and the trigeminal ganglion near the base of the skull. VZV encephalitis may be caused by either varicella (chickenpox) or herpes zoster (shingles). VZV encephalitis must be differentiated from other diseases that cause fever, headache, vomiting, and altered mental status. The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with varicella, most often neonates and the elderly. If left untreated, immunocompromised patients with VZV encephalitis may progress to mortality. Common complications include shock, hypoxemia, and meningitis. Signs of VZV encephalitis include fever, headache, ataxia, and aphasia. Laboratory findings consistent with the diagnosis of VZV encephalitis include leukocytosis and pleocytosis. Magnetic resonance imaging is the imaging modality of choice for VZV encephalitis. Acyclovir is the drug of choice to treat VZV encephalitis.

Classification

Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic.

Pathophysiology

The exact pathogenesis of VZV encephalitis is not fully understood. It is known that VZV encephalitis is the result of the varicella zoster virus, a double-stranded DNA virus within the Herpesviridae family of viruses. The immune system eliminates the virus from most locations upon initial infection, but it remains latent in the dorsal root ganglion and the trigeminal ganglion near the base of the skull. Initial infection by VZV presents as chickenpox, often in children between the ages of 1-9. VZV reactivation, which presents as shingles in adults, is the result of a decline in the frequency of VZV-specific T cells. The molecular basis of reactivation remains unknown. Some histopathologic studies suggest of a postinfectious demyelinating process, while other findings cite direct viral cytopathology.

Causes

VZV encephalitis may be caused by either varicella (chickenpox) or herpes zoster (shingles).

Differentiating VZV Encephalitis from Other Diseases

VZV encephalitis must be differentiated from other diseases that cause fever, headache, vomiting, and altered mental status, such as:

Disease	Similarities	Differentials
Meningitis	Classic triad of fever, nuchal rigidity, and altered mental status	Photophobia, phonophobia, rash associated with meningococcemia, concomitant sinusitis or otitis, swelling of the fontanelle in infants (0-6 months)
Brain abscess	Fever, headache, hemiparesis	Varies depending on the location of the abscess; clinically, visual disturbance including papilledema, decreased sensation; on imaging, a lesion demonstrates both ring enhancement and central restricted diffusion
Demyelinating diseases	Ataxia, lethargy	Multiple sclerosis: clinically, nystagmus, internuclear ophthalmoplegia, Lhermitte's sign; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”) Acute disseminated encephalomyelitis: ; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders
Substance abuse	Tremor, headache, altered mental status	Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, paranoia, sudden panic, anxiety, hallucinations
Electrolyte disturbance	Fatigue, headache, nausea	Varies depending on deficient ions; clinically, edema, constipation, hallucinations; on EKG, abnormalities in T wave, P wave, QRS complex; possible presentations include arrhythmia, dehydration, renal failure
Stroke	Ataxia, aphasia, dizziness	Varies depending on classification of stroke; presents with positional vertigo, high blood pressure, extremity weakness
Intracranial hemorrhage	Headache, coma, dizziness	Lobar hemorrhage, numbness, tingling, hypertension, hemorrhagic diathesis
Trauma	Headache, altered mental status	Amnesia, loss of consciousness, dizziness, concussion, contusion

Epidemiology and Demographics

Incidence

The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with varicella.

Age

VZV encephalitis most commonly affects infants or the elderly.

Gender

Men and women are affected equally by VZV encephalitis.

Risk Factors

Common risk factors in the development of VZV encephalitis include:

• Varicella zoster virus infection
• Immunosuppression
• HIV or AIDS
• Age extremes
• Stress
• Chronic corticosteroid usage
• Skin inflammation
• Pregnancy
• Living in tropical climate
• Working as a physician or other health care provider
• Absence of varicella vaccine

Natural History, Complications, and Prognosis

Natural History

Herpes zoster usually clears in 2 to 3 weeks and rarely recurs. However, if left untreated, immunocompromised patients with VZV encephalitis may progress to mortality.

Complications

Common complications of VZV encephalitis include:

• Shock
• Hypoxemia
• Hypotension
• Aphasia
• Seizures
• Meningitis
• Loss of motor skills
• Coma
• Mortality

Prognosis

Prognosis for VZV encephalitis is generally good in most individuals. Prognosis for VZV encephalitis is poor in immunocompromised individuals.

Diagnosis

History and Symptoms

If possible, a detailed and thorough history from the patient is necessary. Symptoms of VZV encephalitis include:

• Fever
• Headache
• Loss of body control
• Inability to produce or comprehend language
• Seizures
• Cough
• Shortness of breath or labored breathing
• Coughing up blood
• Rash
• Lethargy

Physical Examination

Common physical examination findings of VZV encephalitis include:

• Fever
• Aphasia
• Ataxia
• Nuchal rigidity
• Nystagmus
• Hypertonia or hypotonia
• Hyperreflexia or hyporeflexia
• Positive plantar reflexes
• Hemiparesis

If rash and ataxia are present simultaneously, the clinical presentation is sufficient to establish a diagnosis.

Laboratory Findings

Rapid diagnostic methods, which include polymerase chain reaction (PCR) and direct fluorescent antibody (DFA) assay, are the methods of choice. Polymerase chain reaction testing, the most sensitive test for VZV, can be used for detecting invasive disease, and detects varicella zoster virus in vesicle fluid, serum, cerebrospinal fluid, and other tissues. Direct fluorescent antibody assay is performed on scrapings taken from the base of a skin lesion, and is a rapid and reliable method for diagnosing VZV disease. Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis. Therefore, lumbar puncture may be warranted. Laboratory findings consistent with the diagnosis of VZV encephalitis include leukocytosis and pleocytosis.

CT

Computed tomography may be helpful in the diagnosis of VZV encephalitis. Findings on CT suggestive of VZV encephalitis include subtle low density within the anterior and medial temporal lobe and the insular cortex. Subtleties become more apparent over time and may progress to hemorrhage, and may eventually spread to the other temporal lobe after 7-10 days.

MRI

Magnetic resonance imaging is the imaging modality of choice for VZV encephalitis. Findings on MRI suggestive of VZV encephalitis include:

• T1
  • General edema in the affected region
  • Hyperintense signal if complicated by subacute hemorrhage
• T1 C+ (Gd)
  • Early, enhancement is generally absent
  • Later, enhancement is variable and may appear as:
    • Gyral enhancement
    • Leptomeningeal enhancement
    • Ring enhancement
    • Diffuse enhancement
• T2
  • Hyperintensity of affected white matter and cerebral cortex
• DWI/ADC
  • More sensitive than T2 weighted images
  • Restricted diffusion is common due to cytotoxic edema
• GE/SWI
  • May demonstrate blooming if hemorrhagic

Lumbar Puncture

Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis. Therefore, lumbar puncture may be helpful in the diagnosis of VZV encephalitis. Findings on lumbar puncture suggestive of VZV encephalitis include pleocytosis.

Treatment

Medical Therapy

The mainstay of therapy for VZV encephalitis is antiviral therapy. Acyclovir is the drug of choice to treat VZV encephalitis. Ganciclovir and adjunctive corticosteroids can be considered as alternatives.

Prevention

Varicella vaccine or zostavax is recommended for the most individuals to prevent VZV encephalitis. Other primary prevention strategies include avoiding contact with affected individuals, disinfecting surfaces, and hand washing.