Neuromyelitis optica spectrum disorder after presumed coronavirus (COVID-19) infection: A case report.

Neuromyelitis optica spectrum disorder is an inflammatory autoimmune condition, predominantly affecting the optic nerves and spinal cord. It has been stated that viral infections play a role in the development of neuromyelitis optica. Several murine coronaviruses can cause inflammatory demyelinating diseases, including optic neuritis. Here we report, to the best of our knowledge, the first human case linking a presumed SARS-CoV-2 infection to the development of NMOSD.

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

HIV infection associated neuromyelitis optica spectrum disorder: Clinical features, imaging findings, management and outcomes.

INTRODUCTION: HIV Infection associated NMOSD (HIV-NMOSD) is a recently recognized entity. Management of patients with HIV-NMOSD is a challenge. Here we report our own experience of HIV-NMOSD along with a complete review of all the cases of HIV-NMOSD reported in literature. OBJECTIVE: Describe the clinical features, radiological findings, treatment patterns and outcomes in patients with HIV-NMOSD. METHODS: The details of all cases of HIV- NMOSD were searched from our NMOSD registry. A literature search was also done using the terms NMO, NMOSD and HIV infection in PUBMED, Google Scholar and EMBASE. The details of all the reported cases and cases from our registry were collected and analyzed. RESULTS: Six cases of HIV-NMOSD were identified from the literature and one from our registry. There were four males and three females with age ranging from 8 years to 49 years. Duration of HIV infection ranged from newly detected to 15 years. Optic neuritis followed by myelitis was the commonest presentation, occurring in 5 out of 7 patients. 3 patients were anti-aquaporin 4 antibody positive while 3 were negative and in one anti- aquaporin 4 antibody assay was not done. All patients received immunomodulatory treatment. 5/7 patients had poor recovery from acute attacks but no patient had further relapses while on immunomodulatory treatment and antiretroviral therapy. CONCLUSION: HIV associated NMOSD is a recently recognized entity. A high index of suspicion is needed to diagnose these patients. In all patients with HIV infection presenting with optic neuritis or/and myelitis, anti aquaporin 4 antibody status should be checked and in all patients of NMOSD, HIV infection should be ruled out.

Neuromyelitis Optica and Herpes Simplex Virus 2: A Viral Trigger for Aquaporin-4 Autoimmunity?

The clinical and radiographic spectrum of Neuromyelitis optica spectrum disorder has broadened following the description of the aquaporin-4 antibody. The initial triggering event and reason for disease quiescence between relapses is unclear. We present a case of myeloradiculitis associated with aquaporin-4 antibody and concomitant herpes simplex virus 2 infection.

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

A case of anti aquapolin-4 antibody positive myelitis with hyperhidrosis, following herpes zoster.

We report an acute myelitis in a 53-year-old woman that occurred in 7 days after the diagnosis of Th5-6 herpes zoster. Clinical examination revealed hyperhidrosis of left side of her face, neck, arm and upper chest. She also had muscle weakness of her left leg and sensory impairment for light touch and temperature in her chest and legs. Spinal cord MRI demonstrated a longitudinal T2-hyperintense lesion extending from Th1 to 7. In the axial imaging, the lesion dominantly located in the left side gray matter. Hyperhidrosis, weakness and sensory impairment were improved after intravenous therapy with acyclovir and methylprednisolone. VZV (varicella zoster virus) IgG index of the cerebrospinal fluid was high and serological anti aquaporin-4 antibodies were positive at the time of the admission. This case had both characteristics of VZV myelitis and neuromyelitis optica spectrum disorder. Myelitis relapsed 19 months after the first attack. We believe that sympathetic hyper reactivity due to thoracic spinal cord lesion was responsible for the hyperhidrosis in our patient.

Immunization of mice with a peptide derived from the HTLV-1 TAX1BP1 protein induces cross-reactive antibodies against aquaporin 4.

Antibodies against aquaporin-4 (AQP4) are specific and pathogenetic for Neuromyelitis Optica (NMO). In a previous study, three linear intracellular AQP4 B-cell epitopes were uncovered in NMO patients. A particular epitope showed high-sequence similarity with a segment of the human TAX1BP1 protein, which is necessary for the replication of HTLV-1 virus. The aim of the present study was to investigate whether immunization of mice with the TAX1BP1 peptide could produce specific antibodies against AQP4 epitopes or induce symptoms. Eight C57Bl/6 mice were immunized with TAX1BP1pep in Complete Freund's Adjuvant and eight with adjuvant only. Animals received three subcutaneous injections and sera were obtained before each immunization and at sacrifice. All sera were evaluated by ELISA for antibodies against the TAX1BP1peptide, the homologous AQP4 peptide and all linear AQP4 epitopes. Homologous and cross-inhibition assays were performed to ensure binding specificity, and reactivity against conformational AQP4 epitopes was evaluated by a cell-based assay. Sera from immunized animals showed high reactivity against the immunization peptide, and the homologous AQP4 epitope. Inhibition assays confirmed binding specificity. No antibodies were produced against any other epitopes, either linear or conformational. No clinical or brain inflammatory signs were observed in the animals. The induction of antibodies to an AQP4 epitope in mice immunized with the TAX1BP1-derived peptide suggests that a latent HTLV-1 infection could lead to TAX1BP1 antigen presentation and the production of anti-AQP4 antibodies, probably through T cell-mediated mechanisms. Further studies are needed for exploring triggering factors for NMO especially in HTLV-1-endemic regions.

Epstein-Barr virus persistence and reactivation in neuromyelitis optica.

OBJECTIVE: Epstein-Barr virus (EBV) infection has been thought to be a key environmental factor in the development of multiple sclerosis (MS). The aim of this study is to investigate the association of EBV infection with neuromyelitis optica (NMO). METHODS: We measured levels of serum antibodies against EBV antigens, including anti-viral capsid antigen (VCA) IgM, anti-VCA IgG, anti-early antigen (EA) IgM, anti-EA IgG and anti-EBV nuclear antigen-1 IgG, in 50 patients with NMO (including 12 partial form with antiaquaporin 4 antibodies), 51 patients with MS, and 52 healthy controls, and cerebrospinal fluid (CSF) antibodies in 37 patients with NMO and 33 patients with MS with ELISA. RESULT: Compared with patients with MS and normal participants, patients with NMO more frequently had serum anti-EA IgG antibodies (52%), indicating more active viral replication than patients with MS (26%) and controls (25%). The antibody titres were significantly higher in the NMO group than in the MS (p=0.005) and control (p=0.005) groups. The CSF antibody titres were also higher in patients with NMO than in those with MS (p=0.03). CONCLUSIONS: Our results raise the hypothesis that persistent, active EBV replication is present in NMO, and may contribute to the immunological alterations that play a pathogenetic role in the disorder.

A recurrent longitudinally extensive transverse myelitis with Aquaporin-4(AQP4) antibody after herpes zoster.

Longitudinally extensive transverse myelitis (LETM) is a syndrome that involves three or more vertebral segments in the spinal cord lesion, and it is one of the characteristic features of neuromyelitis optica (NMO) differentiating it from multiple sclerosis. Many studies proved the importance of aquaporin-4 (AQP4) antibody, which plays a vital role in the pathogenesis of NMO. Recent reports suggest that recurrent LETM patients with positive anti-AQP4 antibody titers have a higher chance of converting to NMO, and they are now termed as NMO spectrum disorders (NMOSD). The specific role of AQP4 antibody in NMO is yet to be elucidated but there are reports to bring up the pathogenesis in relation with infectious events. Interestingly, parainfectious NMOSD tends to spare the optic nerve unlike classic NMOSD. Here we report a young woman who was once diagnosed as herpes zoster-related LETM, but later developed as recurrent LETM with positive AQP4 antibody titers, which renders the diagnosis of parainfectious LETM without optic neuritis.

Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

Detection of mumps virus RNA in cerebrospinal fluid of patients with neuromyelitis optica.

Neuromyelitis optica (NMO) is an acute inflammatory disease that preferentially involves the optic nerves and spinal cord. Although many infectious agents, including mumps virus, are postulated to have a role in the pathogenesis of multiple sclerosis (MS), the relationship between NMO and infectious agents remains uncertain. To investigate the relationship between NMO and viruses that have special affinity for the central nervous system, we performed a nested polymerase chain reaction (PCR) to detect mumps virus or enterovirus RNA in cerebrospinal fluid samples from 13 patients with MS, 8 with NMO and 20 with other neurological diseases (ONDs). Nested PCR was positive for mumps virus in 2 (25%) of NMO patients, but in none of those with MS and ONDs. Moreover, nested PCR results became negative in the remission phase in the two PCR-positive NMO patients. Mumps virus may have some role in the pathogenesis of NMO.

A serological analysis of viral and bacterial infections associated with neuromyelitis optica.

To evaluate the role of infections in the development of neuromyelitis optica (NMO), 19 patients positive for anti-aquaporin-4 antibody were screened for 24 viral and bacterial infections. Serological evidence of recent viral infection was found in 7 of 15 patients screened during the acute phase of the neurologic illness, which was a significantly more frequent rate of infection than seen in the control group of 33 patients with neurodegenerative, metabolic, or vertebral diseases (47% versus 15%). Mumps virus and human herpes viruses were the frequent causal agents, although there was no statistical difference in frequency between the two groups. Most patients with identified recent infection had monophasic or recurrent myelitis without evidence of optic nerve involvement and small number of total clinical relapses. Disease history tended to be shorter in patients with identified recent infection than those without, and an expanded long spinal cord lesion in magnetic resonance imaging was rarely found in patients with identified recent infection, although statistical significance could not be shown. These findings indicate that, not single, but various viral infections, can be associated with the development of NMO during the early stages of the illness, although the exact pathogenesis of NMO has yet to be clarified.

Neuromyelitis optica associated with subacute human T-lymphotropic virus type 1 infection.

Although human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy, or tropical spastic paraparesis (HAM/TSP), is usually considered as a progressive myelopathy, a subacute variant has been described. It is unusual for optic neuritis (ON) to be associated with an HTLV-1 infection. Neuromyelitis optica (NMO) is characterised by severe attacks of acute transverse myelitis and ON of unknown aetiology. We report a 61-year-old Afro-Caribbean male patient with subacute HAM/TSP associated with bilateral ON that occurred 5years previously. To our knowledge this is the first report of recurrent NMO syndrome associated with HTLV-1 infection.

Neuromyelitis optica following CMV primo-infection.

We report the case of an acute optic neuromyelitis with rhabdomyolysis in a 34-year-old immunocompetent transsexual patient following a recent cytomegalovirus (CMV) infection. The combination of optic neuropathy and myelopathy is recognized as Devic's syndrome. Clinical presentation was unusual as the recent CMV infection induced rhabdomyolysis and was the suspected trigger of neuromyelitis.

Post-dengue neuromyelitis optica: case report of a Japanese-descendent Brazilian child.

Monophasic neuromyelitis optica (NMO) is a rare form of post-infection acute disseminated encephalomyelitis (ADEM). Cases occurring after dengue virus infection are rare, despite the high prevalence of this disease in tropical and subtropical countries. We report a female patient, 11 years old, of Japanese ancestry and living in North Brazil, who developed NMO 1 week after having had a benign form of dengue fever. The disease was confirmed by the detection of dengue IgM antibodies in serum and cerebrospinal fluid (CSF). Restricted distribution of the lesions in the optic nerve and spinal cord was confirmed by ophthalmological evaluation and magnetic resonance imaging of the brain and spinal cord. Therapeutic intervention with corticotherapy resulted in benign evolution. This is the second report of optic spinal syndrome following dengue virus infection in patients of Japanese ancestry, suggesting an influence of the genetic background in the susceptibility to post-dengue NMO.

[Devic's optic neuromyelitis and viral hepatitis type A. A paediatric case report]. / Neuromyélite optique de Devic et hépatite virale A. A propos d'une observation pédiatrique.

INTRODUCTION: Devic optic neuromyelitis is a rare clinical disease that involves severe transverse myelitis and unilateral or bilateral optic neuropathy. Its pathogenesis would be explained by demyelinization triggered by bacterial or viral infections phenomena. According to several author, prognosis would be better in children. CASE REPORT: We report a case of optic neuromyelitis in an 8-year-old child with an uneventful history who was admitted because he suffered from flaccid tetraplegia and sudden decline of the visual acuity. The ophthalmologic examination revealed bilateral neuropapillitis. The medullary MRI visualized a spreading myelitis with bifocal arachnoiditis. Search for a precipitating infectious factor showed positive IgM for viral hepatitis A. With corticosteroid treatment the child achieved total recovery of vision and recovered motor and sensorial function of the upper limbs and the trunk. Paraplegia with sphincteral disorders persisted. CONCLUSION: This case characterized by the precipitating factor (hepatitis virus A), illustrates this rare syndrome. We present a general review of the pediatric cases reported in the literature.