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

# 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
- 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
- Early, enhancement is generally absent
- Later, enhancement is variable and may appear as:
Gyral enhancement
Leptomeningeal enhancement
Ring enhancement
Diffuse enhancement
- Gyral enhancement
- Leptomeningeal enhancement
- Ring enhancement
- Diffuse enhancement
- T2
Hyperintensity of affected white matter and cerebral cortex
- Hyperintensity of affected white matter and cerebral cortex
- DWI/ADC
More sensitive than T2 weighted images
Restricted diffusion is common due to cytotoxic edema
- More sensitive than T2 weighted images
- Restricted diffusion is common due to cytotoxic edema
- GE/SWI
May demonstrate blooming if hemorrhagic
- 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.