Varicella zoster virus (VZV) causes two distinct clinical diseases. Varicella, is the primary infection and results from exposure of a person susceptible to the virus. The virus remains latent in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia along the entire neuraxis. Years later, in association with a decline in cell-mediated immunity in the elderly and immunocompromised, VZV reactivates and can cause a wide range of neurologic disease, including herpes zoster, postherpetic neuralgia, vasculopathy, myelopathy, retinal necrosis, cerebellitis, and zoster sine herpete [1
]. Although varicella is mainly a childhood disease, VZV is associated with serious complications, such as CNS involvement, pneumonia, secondary bacterial infections, and death [2
]. Older age, immunocompromised state, and possibly pregnancy are risk factors associated with higher severity of varicella [3
]. The danger of dying from varicella is highest in infants and in elderly individuals. Although varicella is more severe in immunocompromised persons, most cases of severe morbidity and mortality are seen in healthy people [4
Most patients are over 60 or immunocompromised [5
]. Bone marrow transplant recipients and HIV-positive patients are at particular risk. Not surprisingly, zoster in otherwise young, healthy individuals may be the first manifestation of HIV infection [6
Extracutaneous sites of involvement include the central nervous system (CNS), as manifested by meningo-encephalitis or encephalitis. The clinical presentation is similar to other viral infections of the brain. Several studies conducted in patients with herpes zoster have demonstrated that subclincal meningeal irritation, indicated by a reactive CSF pleocytosis can occur in many cases [7
]. Herpes zoster can be associated with subtle signs of aseptic meningitis - mild CSF mononuclear pleocytosis with slight increase in protein levels - in up to 50% of patients. The application of PCR to the CSF can be used to detect VZV DNA and, therefore, infections of the CNS. The opportunity to study the characteristics of different viral infections of the CNS has been aided by viral PCR of CSF. While CSF protein levels greater than 1000 mg/dL are considered unusual in viral meningitis, in a recent retrospective study, patients with VZV CNS infection had significantly higher CSF protein levels (median > 974 mg/dL) than did patients with enteroviral CNS infection [8
] A rare manifestation of CNS involvement by herpes zoster is granulomatous cerebral angiitis, which usually follows zoster ophthalmicus [9
Acute inflammatory demyelinating polyneuropathy (AIDP, or Guillain-Barre syndrome) is also a rare neurologic complication of varicella and herpes zoster [10
]. Patients can have symptoms that are similar to other AIDP that follow other infections.
Myelitis is a common complication following herpes zoster and is sometimes referred to as “postinfectious myelitis”. Spinal cord involvement can occur in almost 50% of patients with spinal (cervical, thoracic, and lumbosacral) herpes zoster [11
]. Patients can present with paraparesis, impaired sensation with a level compatible with the segment of VZV reactivation, and sphincter dysfunction. Nevertheless, in the majority of patients, the involvement of the spinal cord is subtle and asymptomatic, and complete recovery is usually achieved.
Another form of VZV myelitis has come to be associated with AIDS patients and is often insidious, progressive, and sometimes fatal. Myeltis in HIV-infected patients involves the spread of VZV from the dorsal root ganglia centrally into the spinal cord parenchyma. CSF exam reveals findings typical of viral encephalitis. Magnetic resonance imaging (MRI) can show longitudinal, serpiginous enhancing lesions. Diagnosis is confirmed with the presence of VZV DNA in the CSF via PCR. Several reports describe zoster myelitis in HIV-infected patients in the absence of any rash and have documented VZV DNA within spinal cord specimens at autopsy [12
Large vessel granulomatous arteritis is usually a disorder of immunocompetent individuals and can follow herpes zoster or varicella [13
]. It is mainly a disorder of the elderly where a brain infarction develops weeks to months following ipsilateral trigeminal zoster and is associated with a mortality of up to 25% [14
]. Cerebral aneurysms and hemorrhage can also develop from viral invasion of the vessels. The CSF can show mild lymphocytic pleocytosis, increased protein, sometimes oligoclonal bands, and PCR is positive for VZV nucleic acid. In cases of VZV vasculopathy, the CSF does not always contain PCR-amplifiable VZV DNA, but does contain anti-VZV IgG [15
]. Because of the high mortality rate, testing via PCR for both VZV DNA and anti-VZV IgG should be done. Angiography reveals focal narrowing or occlusion of the blood vessel which on autopsy displays arterial inflammation with multinucleated giant cells, Cowdry type A inclusion bodies, and VZV nucleic acid [16
Small vessel multifocal vasculopathy usually occurs in immunocompromised patients. It usually occurs without any skin lesions and consists of subacute multifocal neurological deficits along with headache, fever, mental status changes, and seizures [17
]. A history of herpes zoster may precede the symptomatology by several weeks to months. Cerebrospinal fluid analysis is similar to that of large vessel granulomatous arteritis. The MRI typically demonstrates multifocal infarcts and autopsy reveals mixed necrotic and demyelinative lesions with small vessel vasculopathy.
Focal motor weakness is another neurologic complication that may follow herpes zoster. Motor impairment may follow herpes zoster anywhere from one day to several months and usually involves the same segment that was affected by the rash. Arm weakness and diaphragmatic paresis has been associated with herpes zoster in the cervical dermatomes [18
]. Lumbosacral herpes zoster has been associated with leg weakness. Neurogenic bladder and loss of anal sphincter control can follow sacral herpes zoster [19
]. Peripheral facial weakness has been reported with herpes zoster oticus. The prognosis of focal motor weakness is generally fair with more than half of patients regaining full motor power [20
In our patient, the argument can be made that the acyclovir could have been given intravenously. However, a common bedside challenge is to determine whether a case of meningitis has a bacterial or viral etiology, as this will effect antimicrobial selection, which in turn, has its risks and benefits. Seriously ill patients with suspected viral meningitis should probably receive intravenous antiviral therapy. Oral acyclovir can be tried on less severely ill patients, although data on efficacy are lacking. Oral acyclovir was chosen in our patient as she was hemodynamically stable and did not have focal neurological deficits.
Also, in our patient, the CSF glucose/serum glucose ratio was low. Glucose in the CSF normally approximates 60% of the serum glucose level. Low CSF glucose is often seen with bacterial meningitis and is also one of the hallmarks of meningeal carcinomatosis as well as CNS sarcoidosis. The CSF glucose level is typically normal during viral infections. However, low CSF glucose levels can occasionally be observed with mumps, enteroviruses, lymphocytic choriomeningitis, as well as herpes simplex and varicella zoster viruses [21
]. This aspect of our case makes it atypical of most cases of VZV meningitis.
In conclusion, herpes zoster is associated with a wide range of neurologic complications and presentations. Patients who have a dermatomal distribution of VZV and who have headaches should be considered to have VZV meningitis. Virologic confirmation requires testing the CSF for VZV DNA via PCR.