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

Mathew, Thomas; Avati, Amrutha; D'Souza, Delon; Therambil, Manjusha; Baptist, Anita Angela; Shaji, Asha; Nadig, Raghunandan; Rockey, Smitha Mary; Parry, Gareth

doi:10.1016/j.msard.2018.11.014

Cited by 15 publications

(8 citation statements)

References 17 publications

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“…The theory that a viral infection can trigger NMOSD pathogenesis is supported by several case series and case reports demonstrating an association between NMOSD and various viral infections including epstein barr virus, influenza virus, human immunodeficiency viruses (HIV), and varicella zoster virus (9,(44)(45)(46)(47). SARS-CoV-2 infection has joined these other viral agents as a potential risk factor for PNS and CNS demyelinating disease (48,49).…”

Section: Discussionmentioning

confidence: 99%

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review

Harel¹,

Gorman²,

Wallin³

2023

Front. Neurol.

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BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations.ObjectiveThis study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations.MethodsA Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination.ResultsA total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3–120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died.ConclusionThis systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

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Section: Discussionmentioning

confidence: 99%

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review

Harel¹,

Gorman²,

Wallin³

2023

Front. Neurol.

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“…The factors responsible for this clinical heterogeneity, as sought in a study of 14 Asian mother-daughter pairs of familial NMOSD [ 2 ], are uncertain. We cannot directly ascribe case one’s more severe and delayed manifestation of NMOSD to HIV infection because although HIV associated NMOSD is described [ 3 ], HIV’s role in clinical heterogeneity of familial NMOSD is not. Furthermore, NMOSD onset and relapse post COVID-19 vaccination has been described [ 4 ] and therefore each one of our described cases may have an independent pathogenic mechanism for NMOSD but genetic factors are not excluded.…”

Section: Discussionmentioning

confidence: 99%

Different clinical phenotypes of AQP4-IgG positive NMOSD in two first degree relatives

Ssemmanda,

Musubire

2023

BMC Neurol

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Background Neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the CNS in which patients have severe relapses of optic neuritis and myelitis. Aquaporin-4 antibody (AQP4-IgG) positive NMOSD has not been reported in members of the same family in Sub Saharan Africa. We report the uncommon scenario in which both a Ugandan HIV positive woman and her HIV negative daughter were diagnosed with AQP4-IgG positive NMOSD. We discuss pathogenic mechanisms that may underlie familial presentation of AQP4-IgG positive NMOSD. Case Presentation Case 1, a 54-year-old female teacher with a 20-year history of HIV infection and virally suppressed on Tenofovir, Lamivudine and Dolutegravir HAART regimen, presented with 8 months of progressive quadriparesis and urinary incontinence with a T6 sensory level. She had gadolinium enhancing longitudinally extensive transverse myelitis on MRI and was AQP4-IgG positive on serum studies. She received IV Methylprednisone 1 g daily for 3 days as a pulse and was continued on tapering doses of oral Prednisone with maintenance doses of Azathioprine. She showed slow improvements in limb motor function. Her daughter, case 2, is a 35-year-old HIV negative nutritionist, independently ambulant, with no known comorbidities or precedent autoimmune disease. She presented 1 year before her mother’s AQP4-IgG positive NMOSD diagnosis with 7 months history of bilateral visual loss of rapid onset, with gadolinium-enhancing optic nerves on Brain and orbit MRI, in keeping with bilateral optic neuritis. She was AQP4-IgG positive on serum studies. She stabilized on tapered doses of oral Prednisone and continues daily oral Azathioprine with moderate improvement in her vision and no further relapses as yet. Conclusions We add to existing literature and hypothesize that NMOSD appears to show a complex genetic background. To our knowledge, this is the first report in Sub-Saharan Africa, of familial AQP4-IgG positive NMOSD presenting with clinical heterogeneity between first degree relatives. A better understanding of the pathogenic mechanisms involved, including genome wide studies for particular risk loci for familial NMOSD, will be pivotal for future preventative and therapeutic strategies.

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“…A separate discussion needs to be conducted regarding HIV infection associated with NMOSD, an entity that has been recognized only relatively recently. To date, seven cases of HIV-NMOSD have been described worldwide, including both AQP4-positive and AQP4-negative patients and the peculiarity of this disease is the concomitant presence in the same patients of hypo- and hyperactivation of the immune system [ 171 ]. The mechanism of autoimmunity during HIV infection is unclear; however, autoimmune disease may occur when immune competence is still present around the time of seroconversion or during retroviral therapy.…”

Section: Nmosdmentioning

confidence: 99%

“…The mechanism of autoimmunity during HIV infection is unclear; however, autoimmune disease may occur when immune competence is still present around the time of seroconversion or during retroviral therapy. Nevertheless, in one of the reported cases, the onset of NMO was accompanied by a decrease in lymphocyte levels, suggesting the active role of the virus in the development of the disease [ 171 ]. It has been observed that HIV can trigger the immune system through the production of alloantigens, the stimulation of immune cells, the induction of interferon gamma production and the release of pro-inflammatory cytokines [ 171 , 172 ].…”

Section: Nmosdmentioning

confidence: 99%

The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases

Frau¹,

Coghe²,

Lorefice³

et al. 2023

Life

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Multiple sclerosis (MS), neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are inflammatory diseases of the central nervous system (CNS) with a multifactorial aetiology. Environmental factors are important for their development and microorganisms could play a determining role. They can directly damage the CNS, but their interaction with the immune system is even more important. The possible mechanisms involved include molecular mimicry, epitope spreading, bystander activation and the dual cell receptor theory. The role of Epstein–Barr virus (EBV) in MS has been definitely established, since being seropositive is a necessary condition for the onset of MS. EBV interacts with genetic and environmental factors, such as low levels of vitamin D and human endogenous retrovirus (HERV), another microorganism implicated in the disease. Many cases of onset or exacerbation of neuromyelitis optica spectrum disorder (NMOSD) have been described after infection with Mycobacterium tuberculosis, EBV and human immunodeficiency virus; however, no definite association with a virus has been found. A possible role has been suggested for Helicobacter pylori, in particular in individuals with aquaporin 4 antibodies. The onset of MOGAD could occur after an infection, mainly in the monophasic course of the disease. A role for the HERV in MOGAD has been hypothesized. In this review, we examined the current understanding of the involvement of infectious factors in MS, NMO and MOGAD. Our objective was to elucidate the roles of each microorganism in initiating the diseases and influencing their clinical progression. We aimed to discuss both the infectious factors that have a well-established role and those that have yielded conflicting results across various studies.

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

Cited by 15 publications

References 17 publications

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review

Different clinical phenotypes of AQP4-IgG positive NMOSD in two first degree relatives

The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases

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