Presence Of Varicella-zoster Virus DNA Research Articles

Varicella Zoster Virus Related Myelo-Radiculo-Neuropathy: Case Report

Aim: Varicella zoster virus (VZV) infections can cause various neurological syndromes during primary infection or reactivation periods. We report two rare neurological complications of VZV, acute longitudinally extensive myelitis and acute motor axonal neuropathy due to primary chickenpox infection that occurred concomitantly. Case: A 76-year-old female patient presented with skin lesions consistent with chickenpox all over the body and walking difficulty ten days ago. Neurological examination revealed paraparesis and areflexia. Spinal cord magnetic resonance imaging revealed a long-segment transverse myelitis lesion involving the lower cervical and thoracic levels. Elevated protein and the presence of VZV DNA were detected in the cerebrospinal fluid, and VZV IgM was detected in the serum. Two days later, the patient's weakness in her legs increased. Electromyography showed signs of acute axonal motor polyneuropathy. The patient was treated with intravenous immunoglobulin after high-dose steroid and antiviral therapy. Partial recovery was observed. Conclusion: Transverse myelitis and Guillain Barré syndrome are rare complications of VZV infection. Our case is first case where these two neorological conditions related to VZV were seen in the same patient.

Central nervous system infections produced by varicella zoster virus.

Varicella zoster virus (VZV) causes varicella, establishes latency, then reactivates to produce herpes zoster. VZV reactivation can also cause central nervous system (CNS) disease with or without rash. Herein, we review these CNS diseases, pathogenesis, diagnosis, and treatment. The most common CNS manifestation of VZV infection is vasculopathy that presents as headache, cognitive decline, and/or focal neurological deficits. VZV vasculopathy has also been associated with cerebral amyloid angiopathy and moyamoya syndrome. Rarely, VZV will produce a meningitis, encephalitis, cerebellitis, and myelopathy. Pathogenic mechanisms include direct VZV infection of affected tissue, persistent inflammation, and/or virus-induced hypercoagulability. Diagnosis is confirmed by the temporal association of rash to disease onset, intrathecal synthesis of anti-VZV antibodies, and/or the presence of VZV DNA in CSF. Most cases respond to intravenous acyclovir with corticosteroids. VZV produces a wide spectrum of CNS disorders that may be missed as some cases do not have an associated rash or a CSF pleocytosis. Clinicians must be vigilant in including VZV in their differential diagnosis of CNS infections as VZV is a ubiquitous pathogen; importantly, VZV CNS infections are treatable with intravenous acyclovir therapy and corticosteroids.

Varicella-Zoster Virus Infections.

This article describes the clinical features and laboratory and imaging abnormalities of the protean neurologic disorders produced by varicella-zoster virus (VZV) reactivation. Diseases include not only zoster, but also chronic pain (postherpetic neuralgia), meningoencephalitis and cerebellitis, single or multiple cranial nerve palsies (polyneuritis cranialis), myelopathy (myelitis and spinal cord infarction), and VZV vasculopathy of intracerebral and extracerebral arteries that causes ischemic or hemorrhagic stroke, aneurysm, subarachnoid and intracerebral hemorrhage, arterial ectasia, and dissection. The article addresses accurate diagnosis of VZV infection of the nervous system in the absence of rash, and optimal treatment. All neurologic disorders produced by VZV can occur in the absence of rash. Diagnosis is confirmed by the presence of VZV DNA or anti-VZV antibodies in CSF. Based on evidence from recent studies, VZV has been implicated as a cause of giant cell arteritis. Clinicians must be aware that VZV reactivation produces multiple disorders of the central nervous system (CNS) and peripheral nervous system, often without rash. Rapid virologic verification and prompt treatment with antiviral agents can lead to complete recovery, even in patients with protracted disease.

Reply to Gilden et al

TO THE EDITOR—Dr Gilden and his group have proposed that persistent or low-grade productive varicella-zoster virus (VZV) infection occurs in sensory ganglia of patients with postherpetic neuralgia (PHN) [1]. In Nagel’s excellent article [2], an observation that more VZV DNA was present in the saliva of patients with PHN than in saliva from patients without PHN would probably have been interpreted as consistent with this hypothesis, regardless of whether the immune system does or does not control VZV in PHN patients [3]. The fact that the incidence and concentration of prolonged shedding of VZV DNA in saliva was similar in both groups of patients, however, does not support the idea that prolonged replication of VZV causes PHN, although it does not rule it out. We do not know why VZV DNA is present in saliva of patients with herpes zoster and those postinfection [2, 4]. As Dr Gilden and his colleagues note, ganglionitis in PHN has not been directly associated with VZV, possibly, in part, because human ganglia are not readily available for study [1]. Because it is unclear whether the pathogenesis of zoster sine herpete is similar to that of PHN [1], responses to antiviral therapy may not be comparable in each of these conditions. Therefore, because zoster sine herpete responds to antiviral therapy, it does not necessarily follow that PHN will respond in a similar manner. I believe, however, that we can agree that the presence of VZV DNA in saliva and the etiology of PHN remain mysterious and deserve further study [1, 4].

Acute meningoencephalomyelitis due to varicella-zoster virus in an AIDS patient: report of a case and review of the literature

Varicella-zoster virus (VZV) meningoencephalomyelitis is a rare but severe neurological complication of VZV reactivation in immunocompromised patients. We report the case of an HIV-infected individual who developed an acute and severe meningoencephalomyelitis accompanied by a disseminated cutaneous eruption due to VZV. The presence of VZV DNA in cerebrospinal fluid was confirmed by polymerase chain reaction (PCR) technique. The patient started undergoing an intravenous acyclovir therapy with a mild recovery of neurological manifestations. Varicella-zoster virus should be included as a cause of acute meningoencephalomyelitis in patients with AIDS. Early diagnosis followed by specific therapy should modify the rapid and fulminant course for this kind of patients.

Varicella Arthritis in Childhood

Nonbacterial arthritis is a rare but well-recognized complication of acute varicella in children. Reported cases usually described monoarthritis of the knee that occurs at the onset of the rash or shortly after. Herein, we describe a case of arthritis of the hip that occurred in a 4-year-old girl 6 days before the onset of rash. The presence of varicella-zoster virus DNA in synovial fluid was confirmed by real-time polymerase chain reaction. A review of the literature reported 26 previous cases of aseptic arthritis due to varicella infection among children.

Severe Meningoencephalitis Due to Late Reactivation of Varicella-Zoster Virus in an Immunocompetent Child

Recurrent reactivation of latent Varicella-Zoster virus may cause various neurological complications including encephalitis, myelitis, stroke episodes, and meningitis. It occurs mainly in elderly or immunocompromised patients and is very rare in children. We report a 14-year girl who presented with meningoencephalitis due to reactivation of Varicella-Zoster virus 10 years after she had chickenpox and 4 years after she had zoster. Characteristic skin lesions of varicella were absent. Varicella-Zoster virus DNA was detected in cerebrospinal fluid and magnetic resonance imaging (MRI) findings were consistent with small vessel cerebral vasculitis. Treatment with acyclovir and high dose methylprednisolone resulted in near-complete neurological recovery. Although rare, Varicella-Zoster virus may reactivate to cause significant central nervous system disease even in immunocompetent children. Diagnosis depends on a high degree of suspicion because the typical rash may not associate the disease. Characteristic lesions on MRI and the presence of Varicella-Zoster virus DNA in cerebrospinal fluid are key findings for the correct diagnosis.

Varicella‐Zoster Virus in the Saliva of Patients with Herpes Zoster

Fifty-four patients with herpes zoster were treated with valacyclovir. On treatment days 1, 8, and 15, pain was scored and saliva examined for varicella-zoster virus (VZV) DNA. VZV DNA was found in every patient the day treatment was started and later disappeared in 82%. There was a positive correlation between the presence of VZV DNA and pain and between VZV DNA copy number and pain (P <.0005). VZV DNA was present in 1 patient before rash and in 4 after pain resolved and was not present in any of 6 subjects with chronic pain or in 14 healthy subjects. Analysis of human saliva has potential usefulness in the diagnosis of neurological disease produced by VZV without rash.

Herpes Zoster Meningitis Confirmed by Detection of Varicella-Zoster Virus DNA Using the Polymerase Chain Reaction -A case report-

Acute viral meningitis and myositis are rare complications of varicella-zoster virus (VZV) reactivation. A 71-years-old immunocompetent man, who presented with lower back pain radiating to the left lower extremities, developed vesicles on the L5 dermatomal area. The next day, he had complained of aberrant vesicles on the trunk, face and scalp, with generalized myalgia, headache and dizziness. He was confirmed with VZV meningitis and myositis, as demonstrated by the presence of VZV DNA in the blood and cerebral spinal fluid using a polymerase chain reaction (PCR) amplification. PCR has been used in patients with a VZV infection associated neurological symptoms, and provides a useful tool for the early diagnosis of VZV-associated neurological disease. The patient was treated with bed rest, with intravenous acyclovir for the VZV infection, and intravenous Patient-controlled Analgesia for pain management and the prevention of postherpetic neuralgia. When he visited the outpatient department 3 months later, the skin lesion, leg pain, headache and myalgia had all improved, without sequelae. Here, this case is reported, with a discussion of the relevant literature on its diagnosis and management.

Detection of aerosolized varicella-zoster virus DNA in patients with localized herpes zoster.

We examined the excretion of varicella zoster virus (VZV) in hospitalized patients with herpes zoster localized to the thoracic region whose skin lesions were covered with either hydrocolloid dressing agents (hydrocolloid group) or conventional gauze bandages (gauze group). The presence of VZV DNA in swab samples from lesion coverings, the throat, and filters of air purifiers was examined by use of a sensitive polymerase chain reaction assay. For the hydrocolloid group, VZV was detected in none of the samples from lesion coverings or air purifier filters; for the gauze group, VZV DNA was detected in samples from gauze coverings and air purifier filters for all 6 patients. VZV DNA was detected less frequently in throat samples from patients in the hydrocolloid group than in those from patients in the gauze group. The results of the present study suggest that hydrocolloid dressing agents prevent excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster.

Herpes zoster and aseptic meningitis in a previously healthy child

We describe an 8-year-old boy with aseptic meningitis in association with herpes zoster, a rare complication in immunocompetent children. This previously healthy boy, who had a history of chickenpox at the age of 6 months, presented with grouped, painful vesicular lesions of the right thoracic dermatomes 7–9. A clinical diagnosis of herpes zoster was made and symptomatic local treatment was initiated. Five days later the child had an acute onset of intense headache. On physical examination, the boy was in a moderately well condition and subfebrile with an axillary body temperature of 37.8C; all other vital signs were normal. Herpes zoster of the right thoracic wall was still present, however, no vesicles could be found on the face, ear or mouth. Neurological examination revealed a stiffness of the neck with positive Kernig sign and constant bilateral fasciculation of the periorbicular muscles, albeit more pronounced on the right side. Peripheral facial muscle weakness was not present. Lumbar puncture revealed 47 leukocytes/ll with 87% lymphocytes and 13% polynuclear granulocytes. CSF glucose and protein levels were within the respective normal ranges. A differential diagnosis of aseptic meningitis caused by reactivated varicella zoster virus (VZV) or herpes encephalitis was made and treatment with acyclovir i.v. (1500 mg/m 2 /d in three divided doses) was started empirically. Periorbicular fasciculations stopped 6 h after the first dose of acyclovir. Bacterial culture of CSF yielded no growth. VZV DNA was recovered from CSF by polymerase chain reaction (PCR) whereas herpes simplex virus DNA was not detected. VZV antibodies in CSF were not analysed. However, the presence of VZV DNA in CSF was strong presumptive evidence of VZV infection of the central nervous system, and acyclovir treatment was continued for 7 days. The boy’s general condition normalised gradually over the next few days. During 12 months of follow-up, no neurological or cutaneous complications have occurred. Children who contract varicella in the 1st year of life are at increased risk for zoster during childhood, but it is

Detection of varicella-zoster virus DNA in tear fluid and saliva of patients with Ramsay Hunt syndrome

Ramsay Hunt syndrome develops when the varicella-zoster virus (VZV) is reactivated. In the present study, we examined the secretion kinetics of VZV DNA in the tear fluid, submandibular gland saliva and parotid gland saliva of 15 patients with Ramsay Hunt syndrome. The presence of VZV DNA was detected using PCR and a microplate hybridization method. Hybridization signals were measured using the fluorescence density of an enzymatic reaction product using fluoroscan and a system involving streptavidin-conjugated beta-galactosidase. The results were converted into numerical values and used to estimate the number of virus DNA copies. VZV DNA was detected in the tear fluid, submandibular gland saliva and parotid gland saliva of the Ramsay Hunt syndrome patients. The rate of VZV DNA detection in the submandibular gland saliva was 72%, and the detection rate in the parotid gland saliva was 57%. The detection rate in the tear fluid was 27%, which is significantly lower than other two detection rates. Regarding the submandibular gland saliva and the parotid gland saliva, the VZV DNA was detected in samples collected at a comparatively early stage of onset. In the tear fluid, the detection rate increased significantly in samples collected 2 weeks after onset or later. Thus, differences in the detection rate were observed depending on the type of secretory gland and the timing of the sample collection. The VZV DNA in the tear fluid is thought to derive from the ganglion trigeminale. The increase and decrease in the number of VZV DNA copies detected in samples collected at different times is considered to substantiate VZV reactivation in Ramsay Hunt syndrome.

Cutaneous reactions following herpes zoster infections: report of three cases and a review of the literature

Three patients, one healthy and two immunocompromised, developed cutaneous reactions that histologically mimicked granuloma annulare at sites of resolved varicella-zoster virus (VZV) reactivation infections. Variable latency periods between the infection and the granulomatous reaction were noted. As in other case reports, the presence of VZV DNA in these lesions was inconsistently demonstrated by the polymerase chain reaction (PCR) and appears more common in early, as opposed to late, post-zoster granulomas. In addition to various granulomatous reactions, vasculitic and neoplastic eruptions following resolved VZV infections have been described and are reviewed here. Therapeutically, topical, intralesional and systemic corticosteroids, as well as acyclovir, have been tried with inconsistent results. Although the pathogenesis remains unclear, the presence of VZV DNA in early lesions that histologically do not display viral cytopathic changes, suggests the virus induces an atypical delayed hypersensitivity reaction not affected by antiviral therapy.

Reactivated and latent varicella-zoster virus in human dorsal root ganglia.

Ganglia obtained at autopsy were examined by in situ hybridization from one patient with zoster (also called herpes zoster or shingles), two varicella-zoster virus (VZV)-seropositive patients with clinical evidence of zoster, one VZV-seronegative child, and one fetus. Ganglia positive for VZV had a hybridization signal in both neuronal and nonneuronal satellite cells. Ganglia obtained from the fetus and from the seronegative infant were consistently negative for VZV. Two striking observations were evident regarding the presence of VZV DNA in ganglia obtained from the individual with zoster at the time of death. First, ganglia innervating the sites of reactivation and ganglia innervating adjacent sites yielded strongly positive signals in neurons and satellite cells, whereas ganglia from distant sites were rarely positive. Second, VZV DNA was found in both the nuclei and the cytoplasm of neurons innervating areas of zoster. However, in neurons innervating zoster-free areas, VZV DNA was found only in the nucleus of neurons and their supporting satellite cells. Immunohistochemistry with a fluorescent monoclonal antibody to the VZV glycoprotein gpI, a late virus protein, revealed a positive signal in the cytoplasm of ganglia with clinical evidence of reactivation. These results illustrate that both neuronal and satellite cells become latently infected following primary VZV infection. The presence of VZV DNA and gpI in the cytoplasm of neurons demonstrates productive infection following reactivation at the site of latency.