Varicella-zoster Virus Myelitis Research Articles

Frequency of Aquaporin-4 Immunoglobulin G in Longitudinally Extensive Transverse Myelitis With Antiphospholipid Antibodies

Antiphospholipid (aPL) antibodies have historically been postulated to cause a poorly understood inflammatory myelitis. Neuromyelitis optica spectrum disorder (NMOSD) causes an inflammatory longitudinally extensive transverse myelitis (LETM). In 2004, aquaporin-4 immunoglobulin G (AQP4-IgG) was first reported as a highly specific (>99%) serum diagnostic biomarker of NMOSD, distinguishing it from other disorders (eg, multiple sclerosis). We sought to assess the frequency of AQP4-IgG (and thus NMOSD diagnosis) in LETM with aPL antibodies. We searched Mayo Clinic records (from January 1, 1996, through December 31, 2014) for patients with (1) LETM and (2) aPL or β2-glycoprotein I antibodies and (3) a serum sample available. AQP4-IgG was evaluated in the 24 included patients and in 20 controls with aPL antibodies but without myelitis. Seropositivity for AQP4-IgG was confirmed in 11 of 24 patients with LETM (46%), confirming an AQP4-IgG–seropositive NMOSD diagnosis rather than aPL-associated LETM. Six of 11 AQP4-IgG–seropositive patients (54%) were initially diagnosed as having aPL/lupus-associated myelitis. Recurrent LETM was exclusive to AQP4-IgG–seropositive patients (P=.003). Alternative diagnoses assigned to the remaining 13 AQP4-IgG–seronegative patients included idiopathic transverse myelitis (n=5), seronegative NMOSD (n=2), spinal cord infarct attributed to aPL antibodies (n=2), spinal cord sarcoidosis (n=1), varicella-zoster virus myelitis (n=1), postinfectious myelitis (n=1), and multiple sclerosis (n=1). All 20 controls were seronegative for AQP4-IgG. Clotting disorders occurred in 36% of patients (4 of 11) with LETM with both aPL antibodies and AQP4-IgG. AQP4-IgG should be tested in all patients with LETM and aPL antibodies because AQP4-IgG–seropositive NMOSD accounts for almost half of all cases. Clotting disorders are common in patients with LETM with dual positivity for AQP4-IgG and aPL antibodies.

Subacute histopathological features in a case of varicella zoster virus myelitis and post-herpetic neuralgia.

Post-herpetic neuralgia is a crippling complication of varicella zoster virus (VZV) reactivation, also known as zoster disease. In rare cases, VZV spreads to the spinal cord and causes myelitis. There is a paucity of data on spinal cord histopathology in the subacute phase of post-herpetic neuralgia and VZV myelitis. In this report, we present a case of post-herpetic neuralgia in a patient who died 5 weeks after initiation of symptoms. Autopsy limited to the spinal cord revealed severe tissue vacuolization associated with macrophage and lymphocytic infiltration that was most intense in the right posterior horn, corresponding to an area of magnetic resonance imaging (MRI) T2-weighted hyperintensity. There was some extension of the inflammatory response to the ipsilateral posterior column, dorsolateral column, precentral gray matter, and contralateral lateral column. No significant axonal or myelin loss was observed. Nerve roots and meninges were free of significant inflammation. Our findings provide histopathological insight into early subacute changes in post-herpetic neuralgia and suggest the involvement of the cord and subsequent macrophage and lymphocyte inflammatory response may lead to pain fiber irritation and the clinical pain syndrome of post-herpetic neuralgia.

Vanishing spinal cord after varicella-zoster virus myelitis.

Vanishing spinal cord after varicella-zoster virus myelitis.

Neurological Sequale of Varicella Zoster Virus Infection

Background: Varicella-zoster virus meningoencephalitis is an uncommon complication in immunocompetent adults. Typically, most patients present with neurological symptoms within 7-10 days of onset of rash . Also neurological symptoms preceding the rash or in the absence of the rash are rare. Methods: A 50 year-old female experienced urinary and bowel retention and numbness of heel for three days. She had a painful rash on her right thigh eight weeks earlier. MRI was normal. VZV PCR was positive in the CSF. Her neurological symptoms resolved with Acyclovir. A 23 year-old woman experienced left lower extremity weakness and numbness of right leg and abdomen and urinary retention for one week. She had decreased pin prick in right leg up to T8 level. Serum Hepatitis B and Varicella Zoster virus antibodies were positive. MRI showed restricted diffusion and T2/FLAIR hyperintensity in the pons, mid brain and medial temporal lobe. She was treated with steroids and IVIG. After one month she developed fever, blurry vision and vesicular rash on left forearm. Skin biopsy was positive for Varicella zoster virus antibody. Retinal necrosis was found to be consistent with Varicella zoster virus infection. Patient improved neurologically on Valtrex 1 gm TID. An 84-year-old male had symptoms of severe radicular thoracic pain, urinary and bowel incontinence for one week. MRI of the Thoracolumbar spine showed an intradural, intramedullary enhancing lesion at the T7-T8 level with extensive edema. Autopsy revealed viral encephalomyelitis involving the medulla and multiple foci within the spinal cord with inflammation, necrosis, along with Cowdry viral inclusions consistent with Varicella-zoster virus. Conclusion: The above mentioned cases high light atypical presentation of varicella zoster virus infection.The possibility of varicella zoster virus infection should be considered in patients presenting with un explained myelopathy and restricted diffusion changes, mass lesion or un usual CNS symptoms. Importance: Multiple neurologic complications may follow the reactivation of varicella-zoster virus (VZV), including herpes zoster, vasculopathies, myelitis, retinitis, and zoster sine herpete (pain without rash). Myelitis is one of the rarest neurological complications of vzv infection. Observations: We report three cases of VZV myelitis, two of them were immunocompetent and in two myelitis was associated with concomitant cerebral and brain stem strokes. Conclusions and Relevance: In immunocompetent patient VZV myelitis can manifest in the absence of a rash. Diffusion weighted images on MRI can be normal in the setting of acute myelitis due to VZV infection requiring CSF VZV PCR analysis to make prompt diagnosis and appropriate early treatment can lead to full recovery. Oral treatment for VZV rash does not preclude development of myelitis and may require intravenous antiviral medications to treat the infection subsequently. VZV infection can present as mass lesion of the spinal cord. Concomitant cerebral hemisphere and brain stem ischemic lesions and myelitis can occur due to vzv infection.

Longitudinally Extensive Varicella-Zoster Virus Myelitis in a Patient With Multiple Sclerosis

Case report. To report this rare varicella-zoster virus (VZV) complication in a patient with multiple sclerosis. Longitudinally extensive transverse myelitis is a spinal cord lesion that extends over 3 or more vertebral segments. A common feature in neuromyelitis optica, longitudinally extensive transverse myelitis can also occur in several other diseases. A 15-year-old boy with relapsing-remitting multiple sclerosis, who has been treated with immunomodulators for 6 months, developed a subacute left brachiocrural hemiparesis with ipsilateral decreased sensation in the trunk and limbs. This was interpreted as a new relapse and was treated consequently. During the evolution, the patient developed a cutaneous rash in the left C8 metameres, followed by asymmetric tetraparesis. Magnetic resonance imaging demonstrated an extensive cervical-thoracic myelopathy. Cerebrospinal fluid analysis revealed 17 leukocytes per microliter (95% mononuclear), protein 41 mg/dL, and negative VZV-DNA by polymerase chain reaction, but elevated anti-VZV immunoglobulin G cerebrospinal fluid/serum index, with a normal albumin cerebrospinal fluid/serum index, all of which were consistent with intrathecal synthesis of anti-VZV antibody. We were able to rule out all other causes included in the differential diagnosis, namely, vascular disease, tumor, and autoimmune conditions, especially those associated with neuromyelitis optica spectrum disorders. Awareness of the potentially varied presentation of VZV myelitis can enable earlier recognition and specific treatment.

Diagnostic value of a “wide‐range” quantitative nested real‐time PCR assay for varicella zoster virus myelitis

Myelitis is one of the rarest neurological complications of varicella zoster virus (VZV) infection. In this study, the authors remodeled the "wide-range" quantitative nested real-time (QNRT) polymerase chain reaction (PCR) assay to quantitatively detect a small amount of VZV-DNA in cerebrospinal fluid (CSF). For use as a specific internal control "calibrator," an original mutation-VZV (MZ) plasmid was developed. The initial copy number of VZV-DNA in CSF specimens was measured by the amplification rate of the MZ-plasmid. For 17 consecutive CSF specimens collected from three elderly patients with VZV myelitis, the diagnostic value of the wide-range QNRT-PCR assay was evaluated and compared with other conventional PCR assays and enzyme immunoassay (EIA). The MZ-plasmid demonstrated statistically uniform amplifications (F=1.016) against a wide range (1-100,000) of copy numbers of mimic VZV-DNA. The wide-range QNRT-PCR assay quantitatively and rapidly (within 48 hr) detected 5,863, 3,052, 958, and 6,721 copies/ml of VZV-DNA in the CSF specimens collected from all patients in the acute phase. Additionally, there was a significant difference (*P=0.023) in the copy number of VZV-DNA between before and after acyclovir treatment. Other conventional single PCR assays all revealed negative results, but were nevertheless time-consuming (7 days). The IgG EIA-value for VZV was continually elevated throughout the clinical course of all patients. The MZ-plasmid was thus regarded as an appropriate "calibrator" in the wide-range QNRT-PCR assay. This assay is a novel, rapid, accurate, quantitative, and highly sensitive technique, and will contribute as a reliable and useful clinical examination for the rapid diagnosis of VZV infection to central nervous system.

Complications of varicella zoster virus reactivation.

Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of cerebrospinal fluid (CSF), serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IgM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants, gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir.

Features of varicella zoster virus myelitis and dependence on immune status

BackgroundMyelitis is a rare complication of varicella zoster virus (VZV) infection and is more prevalent in immunocompromised individuals. Clinical features, outcomes, and presentations vary. The aim of the current study was to compare the clinical presentations of our patients with those reported in the literature, and to evaluate the differences in clinical features between immunocompromised and immunocompetent patients. MethodsA review of the literature on VZV myelitis was carried out by searching PUBMED from 1980 to 2012. Clinical features of our cases and those in the literature were compared. ResultsThere were 5 cases at our hospital and 26 were reported in the literature. Seventeen patients were immunocompromised (54.8%), and most had acquired immune deficiency syndrome (AIDS). Typical presentations (skin lesions followed by myelopathy at the corresponding level) were observed in 14 patients (45.2%). The immunocompromised patients were prone to atypical presentations (p<0.05). Outcomes were good in immunocompetent patients and relatively poor in immunocompromised patients (p<0.05). Anti-herpetic agents had no statistically significant effect on outcomes in immunocompromised patients (p=0.280), but could reduce mortality rate in AIDS patients (p<0.05). ConclusionImmunocompromised individuals are susceptible to this disease, and prone to atypical presentations and poorer outcomes. Timely recognition and anti-herpes therapy may be beneficial to the outcomes. In the AIDS patients, anti-herpes therapy can reduce mortality effectively.

抗体価指数による髄腔内抗体産生の評価が病因診断確定に有用であったｚｏｓｔｅｒ ｓｉｎｅ ｈｅｒｐｅｔｅにともなう脊髄炎の１例

A previously healthy 55-year-old woman developed abnormal sensation on the right occipital region. It expanded for the following three weeks. On admission, examination revealed abnormal and decreased sensation in touch and pinprick at right C2 to C6 dermatome without skin lesion. There was no muscle weakness. Deep tendon reflexes were more active in the right than in the left. MRI demonstrated a lesion of isointensity on T1-weighted, hyperintensity on T2-weighted, which was enhanced with contrast material on gadolinium-enhanced T1-weighted image at the upper cervical spinal cord corresponding to C2. Laboratory studies showed no immunosuppression and autoantibodies. The antibody index to varicella-zoster virus (VZV) was elevated in the cerebrospinal fluid (CSF). This finding prompted us to a diagnosis of myelitis of zoster sine herpete. VZV is thought to be a causative agent in cases of CNS infections of unknown etiology such as myelitis, even in the absence of skin manifestations. Amplification of VZV DNA by PCR in the CSF and the detection of an intrathecal production of anti-VZV antibodies have important diagnostic value, although their presence depends on the timing of the CSF sampling. The percentage of PCR-positive cases drops after seven or ten days, whereas that of specific antibodies-positive cases elevates. Because VZV myelitis are usually protracted, PCR does not always provide an exquisite sensitivity. Thus, the evaluation of antibody index provides the evidence of intrathecal production of anti-VZV antibodies. That is expressed as CSF antibody titer/serum antibody titer/CSF IgG/serum IgG. This quotient superior to 1.5 or 2.0 suggests CNS synthesis. As the sample of our patient was taken relatively late, this value was diagnostic. We would like to emphasize the importance of making precise diagnosis and adequate initial treatment in patients with myelitis of unknown etiology even if there is no skin lesions.

Atypical symptoms in patients with herpesvirus DNA detected by PCR in cerebrospinal fluid

Background Polymerase chain reaction (PCR) detection of herpesvirus DNA in cerebrospinal fluid (CSF) is an important tool in the diagnosis of central nervous system (CNS) syndromes. The corresponding viral infections present with diverse clinical signs, which are often classical although no sign can be considered as specific. This retrospective study aims to describe atypical symptoms in patients with herpesvirus DNA detected in CSF by PCR. A total of 3452 cerebrospinal fluid samples from patients with suspected herpesvirus infection of the CNS were investigated between 1998 and 2003 in our clinical virology laboratory. “In-house” PCRs for each herpesvirus [herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV), or human herpes virus 6 (HHV6)] were used until 2001 and a commercially available “Herpes Consensus PCR” was used thereafter. One of the five herpesviruses investigated in this study was found in 71 (2.1%) of CSF samples (37 HSV, 14 VZV, 1 CMV, 9 EBV and 10 HHV6). These samples were obtained from 62 patients whose clinical findings were generally consistent with the PCR data. However, some little known features of herpesvirus-related symptoms, such as partial seizure associated with HSV infection, and unusual VZV or HHV6-related myelitis were also observed.