Varicella Zoster Virus and the Nervous System

More than just shingles

Varicella zoster virus (VZV) is at the center of wide range of painful health conditions. Initially, it just causes chickenpox and then it leads to shingles.Usually, though the virus doesn’t actually go away when the rash subsides. Instead, the virus goes into hiding, lurking in ganglionic nerve cells near the spinal cord, waiting for an opportunity to make another appearance.

Shingles is one of the best-known ways VZV returns for round two. The virus creeps out along the skin innervated by one particular nerve, leading to an excruciating rash. Even after the rash vanishes, pain may persist in what is called postherpetic neuralgia.

Shingles is relatively well known but VZV can sometimes lead to vasculitis, meningoencephalitis, myelopathy, vasculopathy, or Ramsay Hunt syndrome.All of these disorders may occur without a rash or months after a rash. Common laboratory evaluations such as the presence of VZV DNA or abnormal cells in cerebrospinal fluid (CSF) are helpful if present, but the disease can occur even if these findings are absent. Even if clinically suspected, the treatment of neurologic diseases caused by VZV can be challenging.

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Herpes Zoster

Herpes zoster, also called shingles, is one of the most widely recognized forms of VZV infection. Because it presents with a characteristic rash, some people don’t think of it as a neurological disorder. However, the rash spreads over what is called a dermatomal distribution, meaning an area of skin innervated by one particular nerve root. This is because that nerve root, or ganglion, is where the virus laid dormant until it had the opportunity to activate again. In fact, magnetic resonance imaging (MRI) may show enhancement of the affected ganglion. The disorder is very painful. Treatment is with valacyclovir for about seven days.

Postherpetic Neuralgia

Postherpetic neuralgia further highlights the fact that herpes zoster is fundamentally a neurological illness. Even after the rash disappears, pain over that dermatome can persist. If it does so for more than three months, a diagnosis of postherpetic neuralgia (PHN) can be made. The most important risk factor for developing PHN is age, with 60–70%  of those over the age of 60 with shingles going on to develop PHN.

The disease may be due to chronic inflammation due to persistent viral infection, as chronic inflammatory cells have been found in people with PHN,,and VZV DNA and proteins found in the blood of many patients with PHN. 

It can be very difficult to control the pain of PHN. A tricyclic antidepressant, gabapentin, pregabalin or lidocaine patches are usually the first line of therapy, followed by opioids, tramadol, or capsaicin as second or third-line treatments. A combination of treatments may be more effective. Percutaneous peripheral nerve field stimulation, in which stimulating electrodes are placed under the area of most pain, may also offer relief.

Zoster Sine Herpete

Essentially, "zoster sine herpete" would be considered postherpetic neuralgia, but there was never any vesicular rash (herpete) to begin with. The disease can be detected by antibody in CSF. Other causes of radicular pain, such as diabetic radiculopathy or nerve impingement, must also be ruled out by neuroimaging studies. Treatment involves high-dose acyclovir, with the treatment of pain in a fashion similar to PHN.

Retinal Necrosis 

Infection of the eye with VZV can cause progressive cell death in the retina. This causes pain near the eye, as well as hazy vision. Peripheral vision is lost first. When a doctor does a fundoscopic exam they may see hemorrhages and whitening of the retina. Other viruses, like HSV and cytomegalovirus, can also cause retinal necrosis.


The term meningoencephalitis refers to inflammation of the brain and surrounding tissues. This can cause headaches, cognitive changes, and focal neurological symptoms or signs such as trouble speaking or weakness on one side of the body. This can all occur even without the telltale rash. An MRI may show enhancement of the tissues surrounding the brain, and a lumbar puncture may show anti-VZV IgG and IgM antibodies or VZV DNA in the cerebrospinal fluid. Treatment is with high-dose intravenous acyclovir.


Myelopathy means damage to the spinal cord. This can lead to progressive weakness of the legs, as well as numbness or incontinence of bladder and bowel. An MRI may show a large lesion or stroke within the spinal cord. Cerebrospinal fluid studies may show the same findings expected in VZV meningoencephalitis, with anti-VZV antibodies or VZV DNA. As with VZV meningoencephalitis, treatment is with high-dose intravenous acyclovir.


VZV can impact the blood vessels of the brain and nervous system, leading to complex patterns of symptoms caused by decreased blood flow.This may lead to headaches, cognitive changes, and focal neurological signs and symptoms. An MRI will show lesions predominantly near the grey-white junction, usually deep within the brain.Sometimes, VZV can target the temporal artery, resulting in a temporal arteritis with loss of vision and pain near the eye. CSF studies are similar to that found in meningoencephalitis or myelopathy, and treatment involves high-dose IV acyclovir.

Ramsay Hunt Syndrome

In addition to the dorsal root ganglia around the spine, VZV can be latent in the ganglia of the cranial nerves as well. When the virus reactivates in cranial nerve ganglia, it can produce distinctive symptoms known as Ramsay Hunt syndrome, which can cause facial weakness akin to Bell’s palsy, as well as several other symptoms. The classic sign of Ramsay Hunt is a vesicular rash within the membrane of the ear

Prevention of Zoster Related Illness

VZV is latent in up to 90% of people. A VZV vaccine was introduced in 2006 to boost immunity to VZV reactivation. The vaccine is currently recommended for immunocompetent individuals over the age of 60 if there has been no recent history of zoster. Despite its effectiveness, the vaccine is underused, and disparities in uptake based on race and ethnicity have also been noted.

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Additional Reading

By Peter Pressman, MD
Peter Pressman, MD, is a board-certified neurologist developing new ways to diagnose and care for people with neurocognitive disorders.