Case Of Neuromyelitis Optica Spectrum Disorder Research Articles

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder

BackgroundSphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). MethodsWe measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). ResultsWe investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14—a significant contributor to differentiating EDSS > 3.0—positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. ConclusionPlasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Big Data Analysis of Inflammatory Conditions Associated With Optic Neuritis.

Previous studies in the United States established multiple sclerosis (MS) as the most common cause of optic neuritis (ON). ON can be associated with other systemic inflammatory conditions including sarcoidosis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and lupus; however, prospective studies to establish risk of ON associated with these diseases are lacking. Furthermore, appropriate workup for ON is still debated. A deidentified electronic medical record of a tertiary care academic center was searched for ON and rheumatologic/neuro-inflammatory diseases in the medical history, diagnoses, and laboratory results; followed by the intersection of ON with each condition. We calculated frequency of systemic conditions among patients with ON and prevalence of ON in those conditions. We also calculated relative risk (RR) of underlying systemic conditions among patients with ON compared with the study patient population. In 6.7 million charts, 5,344 cases of ON were identified. Among those, MS occurred most commonly (20.6%), followed by NMOSD (10.5%). Conversely, ON occurred in 98.4% of NMOSD cases, 53.3% of MOGAD, and 10.0% of MS. NMOSD (RR = 1,233), MOGAD (RR = 688), and MS (RR = 126) had the highest RR among the conditions we evaluated. The subset analysis showed similar findings. The high RR for ON among patients with NMOSD and MOGAD suggests that clinical suspicion for ON should be high among patients with these conditions presenting with vision changes. Conversely, MS and NMOSD should initially be high on the differential diagnosis for any patient presenting with optic neuritis.

Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-related demyelinating defect. Long non-coding RNAs (lncRNAs) might influence the pathobiology and progression of NMOSD. The current study assessed expression level of NEAT1, PANDAR, MEG3 and TUG1 lncRNAs in the peripheral blood of NMOSD patients compared with healthy individuals. All mentioned lncRNAs were shown to be over-expressed in total NMOSD cases, male NMOSD cases and female NMOSD cases compared with the matching control subgroups. MEG3 had the most robust over-expression in patients subgroups compared with normal subjects. There was no noteworthy difference in the expression of any of lncRNAs between female and male patients. MEG3 had an ideal performance in the differentiation of NMOSD cases from healthy persons (Sensitivity and specificity values = 100%). Other lncRNAs could also efficiently separate NMOSD cases from control subjects (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively). Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD.

Epidemiologic and clinical characteristics of neuromyelitis optica spectrum disorder patients, A seven years follow-up study from Iran.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare neuroinflammatory disease characterized by recurrent relapses. The most common signs are myelitis and optic neuritis. It can also present by cerebral or brain stem syndromes. There are still many challenges in its diagnosis and treatment, and long-term follow-up studies are needed to see the disease course over time. We established an electronic registration system of NMOSD patients starting from October 2015 in Kashani hospital, Isfahan, Iran. Every suspected patient was documented and included in the follow-up system to survey their disease course. Anti-aquaporine 4 (AQP4) antibody checked for all by cell-based assay method. All information such as demographic and clinical data and laboratory and MRI findings were documented. Participants were followed up for any relapses, new paraclinical tests and drug changes. This study is based on the definite NMOSD cases (according to the 2015 criteria) characteristics and clinical course during 7 years of registration. The study included 173 NMOSD cases and 56 ones were seropositive for AQP4 Ab. Their mean age was 40.02±11.11 years (45.78 in the seropositive group). The mean age at disease onset was about 30.16 years. The mean time of follow-up by our registration system is 55.84±18.94 months (54.82 months in seropositive ones). The annual relapse rate is estimated as 0.47±0.36. Long extended transvers myelitis (LETM) was present in the baseline MRI of 77 patients (44.5%), while 32 of them did not show any related clinical symptoms. 124 patients revealed an abnormality in the first brain MRI. 27 individuals suffer hypothyroidism as the most common comorbid disease. The disease seems to be more prevalent in the west and southwest areas of Isfahan province. The mean age of onset is higher than Multiple Sclerosis (MS) patients, but there are notable pediatric cases too. It should also be noticed that cervical LETM can be asymptomatic at first. Brain MRI abnormalities are frequently observed. The disease is more prevalent in the geographical areas where showing high MS prevalence.

The Coexisting Neuromyelitis Optica Spectrum Disorder and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Neuromyelitis Optica (NMO), or Devic's disease, is an immune-mediated, usually relapsing, central nervous system (CNS) demyelination disorder associated with optic neuritis and transverse myelitis. It is characterised by the presence of longitudinally extensive transverse myelitis (LETM) and antibodies against water channel aquaporin-4 (AQP4-immunoglobulin G [IgG]). The term NMO spectrum disorder (NMOSD) includes patients with limited forms of NMO who are at risk of recurrence. Often patients with NMO or NMOSD have an associated systemic autoimmune disease, most commonly systemic lupus erythematosus (SLE) or Sjogren syndrome (SS) or a related profile of non-organ-specific autoantibodies. The intriguing aspect of coexisting NMOSD and SLE is whether they are independent diseases that can coexist with each other or the serological findings specific to both diseases in a patient is a non-specific finding of no prognostic or therapeutic concern. We have presented two cases of NMOSD coexisting with SLE and based upon the existing evidence in the literature we present that the two conditions are independent of each other, and, at times, it can throw a therapeutic challenge to any clinician.

The prevalence and clinical phenotype of dual seropositive neuromyelitis optica spectrum disorders at a national reference center in South Asia.

Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune syndrome that is frequently positive for Aquaporin 4 (AQP4) IgG or Myelin Oligodendrocyte Glycoproteins (MOG) IgG. However, dual positivity to both is rare. To assess the prevalence of dual-positive NMOSD and outline its clinical phenotype. This is a retrospective cross-sectional study conducted at a tertiary healthcare center in South Asia between August 2018 and November 2021. The serum and/or CSF samples of suspected cases of NMOSD were tested for both AQP4-IgG and MOG-IgG using an Indirect immunofluorescence test on transfected cells. During the study period, 1935 cases of NMOSD were tested for both antibodies- 65 patients (3.35%; 57 females and 8 males) tested positive for AQP4-IgG, 217 patients (11.21%; 122 females and 95 males) tested positive for MOG-IgG and 3 patients (0.15%; 2 females and 1 male) showed dual positivity. There was a strong female preponderance in all three groups (87.69%, 56.22%, and 66.66% respectively). This study identified 3 patients with dual positivity. The first patient (42 years, Male) presented with area postrema syndrome initially and subsequently relapsed by developing right-sided numbness of the temporal area and limbs during which he tested dual positive. The second patient (27 years, Female) presented with bilateral optic neuritis (left>right) initially and subsequently relapsed following an episode of a seizure with left-sided hemiplegia. The third patient (25 years, Female) initially presented with acute bilateral optic neuritis and later developed left-sided hemiplegia post-recovery at which point she tested dual positive. Management using methylprednisolone was ineffective for all three patients, however, plasmapheresis and/or periodic rituximab injections produced an excellent response. Our study reports that the prevalence of dual-positive NMOSD is 0.15% and its clinical phenotype is more similar to NMO rather than MOG- associated disease.

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

Neuromyelitis 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. This study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations. A 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. A 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. This 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.

Familial neuromyelitis optica spectrum disorders: Case series and systematic review.

Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

Relevance of Bright Spotty Lesions (BSLs) in Neuromyelitis Optica Spectrum Disorders (NMOSD): A Case Series (P1-3.013)

<h3>Objective:</h3> To highlight the diagnostic value of bright spotty lesions (BSLs) as a neuroimaging marker for neuromyelitis optica spectrum disorder (NMOSD). <h3>Background:</h3> NMOSD is an autoimmune central nervous system disease with a complex clinical course. Although longitudinally extensive transverse myelitis (LETM) is a significant magnetic resonance imaging (MRI) finding, it is not unique to NMOSD and is seen in various causes of myelitis. BSLs, defined as hyperintense intramedullary lesions on axial T2-weighted images, are a recent neuroimaging discovery whose specificity and ability to differentiate NMOSD from other demyelinating disorders have not been entirely investigated. <h3>Design/Methods:</h3> A single-center retrospective study of patients recruited at the Department of Neurology, West Virginia University, was conducted between August 1st, 2013, and February 28th, 2022. Eleven confirmed cases of seropositive NMOSD were included from a total of 37 patients. Comparison studies were done with a control group (n=18) of alternative causes of myelitis, including multiple sclerosis, idiopathic transverse myelitis, and neurosarcoidosis. All patients underwent MRIs of the brain and cervico-dorsal spine using our Siemens MAGNETOM® Verio 3.0T and MAGNETOM® Aera 1.5T machines, and two neuroradiologists manually reviewed the scans. <h3>Results:</h3> We report 11 seropositive NMO cases, all seen in women from 25–75 years at the time of diagnosis (most were older than 65). Presentations were diverse, including paresthesia, extremity weakness, and visual changes. Five of the 11 NMOSD patients (45%) had BSLs on spinal MRI, compared to none in the control group; of these, four (80%) also demonstrated LETM. Treatment with immunotherapy and symptomatic management led to clinical improvement in all cases. <h3>Conclusions:</h3> Axial-BSLs are a newly defined spinal MRI finding with high specificity for NMOSD, which can be used in combination with LETM to enhance their diagnostic potential. The absence of BSLs in our control group establishes its prolific role in distinguishing NMOSD from other etiologies of myelitis. <b>Disclosure:</b> Miss Beard has nothing to disclose. Dr. P has nothing to disclose. Dr. Sharma has nothing to disclose. Mrs. Jaiswal has nothing to disclose. Dr. Sriwastava has nothing to disclose.

Neuromyelitis Optica Spectrum Disorder Mimicking Pontine Stroke - A Cautionary Tale: Case Report and Systematic Literature Review (P13-5.014)

<h3>Objective:</h3> To report an unusual clinical pattern of Neuromyelitis Optica Spectrum Disorder (NMOSD) presenting as a pontine stroke mimic <h3>Background:</h3> A 58-year-old Hispanic woman presented to an outside hospital with right-sided numbness, blurry vision, and gait instability. Findings on brain MR imaging were thought to reflect acute pontine stroke; the patient commenced dual antiplatelet therapy. Three weeks later, she presented to our hospital with right-sided hemiparesis. Stroke workup was unrevealing for specific pathophysiology. She was readmitted about two weeks later with a new-onset right cranial nerve VI palsy with ipsilateral facial droop and tinnitus. Brain MRI demonstrated foci of diffusion restriction on DWI in the periventricular white matter and brainstem region suggesting rhombencephalitis of inflammatory or autoimmune origin. Despite IVIG infusion, the patient’s condition deteriorated and she was intubated for airway protection. Serological assays were positive for AQP4 and negative for all other autoantibodies, including anti-Gq1b. She was treated with methylprednisolone pulse dosing and plasmapheresis, followed by rituximab, with significant neurological improvement. <h3>Design/Methods:</h3> In addition to the case report, a systematic literature review was performed to identify NMOSD cases initially diagnosed as stroke. Publications were selected and curated in accordance with PRISMA guidelines. <h3>Results:</h3> Six NMOSD patients were initially thought to represent acute stroke. However, the persistence, progression, or recurrence of symptoms with additional history, follow-up neuroimaging, and further serological immune assays facilitated the accurate diagnosis of NMOSD. Notably, the age of onset in all cases was significantly more advanced than patients normally presenting with NMOSD (median age 32–41). <h3>Conclusions:</h3> NMOSD diagnosis should be considered in individuals presenting with atypical stroke-like symptoms, particularly in those greater than or equal to 41 years of age. This is important as early recognition and treatment with immune therapies can improve functional outcome. <b>Disclosure:</b> Dr. Huang has nothing to disclose. Dr. Arora has nothing to disclose. An immediate family member of Dr. Diamond has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Consultant360. An immediate family member of Dr. Diamond has received publishing royalties from a publication relating to health care. Dr. McFarlane has nothing to disclose. Dr. Najjar has nothing to disclose.

Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids.

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.

Familial Neuromyelitis Optica: A Case Report and Literature Review

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune rare disorder that involves the endfeet of astrocytes. The role of genetics in the disease is not well known. Rare cases of familial NMOSD were reported worldwide. In this report, first, we presented a young man with myelitis and his cousin who suffered from this disease. Then we reviewed some reports around the world about familial NMO. The prevalence of familial NMO is nearly 3%. First cases are reported from East Asia. Its characteristics are similar to the sporadic type. Recent data suggest genetics play role in NMO.

Adding erythropoietin to intravenous methylprednisolone in acute treatment of attacks of neuromyelitis optica spectrum disorders: A randomized controlled trial.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that prompts immediate potent treatment. Delaying treatment could leave debilitating sequelae. As erythropoietin (EPO) has shown neuroprotective effects, we studied the effects of adding EPO to intravenous methylprednisolone (IVMP) in patients with acute attacks of NMOSD. Methods: NMOSD cases with acute attacks were included. Cases of optic neuritis (ON) and those with myelitis were separated. After randomization [with block sizes of 2 (1:1 ratio)], the patients in the intervention group received IVMP 1000 mg/day and intravenous (IV) EPO 20000 U/day for five days. IVMP 1000 mg/day and normal saline (NS) were administered in the control group. Staged eye score and motor forces were evaluated in the patients with ON and myelitis, respectively, at the time of the attack and three months later. Primary patient allocation and clinical assessments were blinded to the physicians. Results: Mean age of participants was 53.87 ± 11.53 years. At follow-up, in the ON arm, the median improvement in staged eye score was 2 in the control and 5 in the intervention group. The difference was significant (P < 0.001). In the myelitis group, none of the patients in the control group had improvement in motor forces. All the patients in the intervention group showed substantial improvement with minimal or no remaining weakness. The difference was statistically significant (P = 0.029). Conclusion: The results show the possible benefit of adding EPO to the classic IVMP in attacks of NMOSD in both visual and motor aspects.

A case report of neuromyelitis optica spectrum disorder induced by pembrolizumab treatment for lung adenocarcinoma: a clinical and immunohistochemical study

BackgroundWe report a case of neuromyelitis optica spectrum disorders (NMOSD), who developed after the pembrolizumab treatment, an immune checkpoint inhibitor, against lung adenocarcinoma. The present case is discussed with the lung adenocarcinoma specimen which was stained by aquaporin-4 (AQP4) and with literature review of NMOSD linked to immune checkpoint inhibitors.Case presentationA 62-year-old Japanese man presented with acute diencephalic syndrome, left optic neuritis, and myelitis 5 months after initiation of pembrolizumab treatment for lung adenocarcinoma. He was diagnosed with NMOSD based on serum anti-aquaporin-4 (AQP4) antibody positivity. Immunohistochemistry of lung biopsy samples showed AQP4 expression on CD68+ cells. This is the fifth reported case of AQP4+ NMOSD triggered by an immune checkpoint inhibitor and the first with a brain lesion. Four out of five NMOSD cases, including the present case and one case with lung metastasis, had lung cancer.ConclusionsImmune checkpoint inhibitors may trigger AQP4+ NMOSD owing to their molecular similarity to AQP4 expressed in lung and glial tissues. Prompt brain/spinal cord imaging and anti-AQP4 antibody testing may facilitate early diagnosis of immune-mediated adverse event in central nervous system associated with immune checkpoint inhibitors.

The Prevalence and Clinical Phenotype of Dual Positive Neuromyelitis Optica Spectrum Disorders (NMOSD) at a National Reference Centre

Objective To assess the prevalence of dual positive NMOSD and outline its clinical phenotype. Background Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune syndrome that is frequently positive for Aquaporin 4 (AQP4) IgG or Myelin Oligodendrocyte Glycoproteins (MOG) IgG. However, dual positivity to both is rare. Design/Methods This is a retrospective cross-sectional study conducted at a tertiary healthcare center in South Asia between August 2018 and November 2021. The serum and/or CSF samples of suspected cases of NMOSD were tested for both AQP4-IgG and MOG-IgG using an Indirect immunofluorescence test on transfected cells. Results During the study period, 1935 cases of NMOSD were tested for both antibodies- 65 patients (3.36%; 57 females and 8 males) tested positive for AQP4-IgG, 217 patients (11.23%; 122 females and 95 males) tested positive for MOG-IgG and 3 patients (0.15%; 2 females and 1 male) showed dual positivity. There was a strong female preponderance in all three groups (87.69%, 56.22% and 66.66% respectively). This study identified 3 patients with dual positivity. The first patient (42 years, Male) presented with area postrema syndrome initially and subsequently relapsed by developing right-sided numbness of the temporal area and limbs during which he tested dual positive. The second patient (27 years, Female) presented with bilateral optic neuritis (left &gt;right) initially and subsequently relapsed following an episode of a seizure with left-sided hemiplegia and right-sided facial deviation. The third patient (25 years, Female) initially presented with acute bilateral optic neuritis and later developed left-sided hemiplegia post-recovery at which point she tested dual positive. Management using methylprednisolone was ineffective for all three patients, however, plasmapheresis and/or periodic rituximab injections produced an excellent response. Conclusions Our study reports that the prevalence of dual positive NMOSD is 0.15% and its clinical phenotype is more similar to NMO rather than MOG- associated disease.

AQP4-MOG Double-Positive Neuromyelitis Optica Spectrum Disorder: Case Report with Central and Peripheral Nervous System Involvement and Review of Literature

(1) The co-occurrence of AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with demyelinating disorders is extremely rare. In addition, a concomitant involvement of the peripheral nervous system (PNS) has been described either in association with AQP4 antibodies-positive neuromyelitis optica spectrum disorder (NMOSD), or MOG-associated disease. We report on a case of NMOSD with co-occurrence of AQP4 and MOG antibodies and concomitant central and peripheral nervous system involvement. We also reviewed available cases of AQP4-MOG double-positive patients. (2) Brain and spine MRI, cerebrospinal fluid studies, and electrophysiological test were performed. Serum AQP4 and MOG positivity was assessed with live cell-based assay. (3) A 62-year-old woman presented with recurrent optic neuritis, myelitis, and radiculitis, tested positive for AQP4 and MOG antibodies, and was treated successfully with rituximab. (4) Although few cases of AQP4-MOG double-positive patients were already described mostly affecting females with a concomitant spinal cord and optical nerve involvement, we describe the first case of double-positive NMOSD with the peculiar involvement of both central and peripheral nervous system.

Aquaporin-4 IgG neuromyelitis optica spectrum disorder onset after Covid-19 vaccination: Systematic review

Neuromyelitis optica spectrum disorder (NMOSD) is rarely reported following Coronavirus disease 2019 (COVID-19) vaccination. We identified 16 cases of new onset NMOSD with positive aquaporin-4 IgG (AQP4-IgG) following COVID-19 vaccination. Transverse myelitis was the most common clinical presentation (75%). Most patients received high dose steroids for acute treatment and maintenance therapy was started in 12 patients (75%). Twelve patients (75%) had improvement of their symptoms at the time of discharge or follow-up. The included cases share similar epidemiology and natural course to non-vaccine related cases. Clinicians should be aware of possible post-vaccination NMOSD to help with earlier diagnosis and treatment.

Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.

Neuromyelitis Optica Spectrum Disorders in Black African: Experience of Togo (2015-2020).

Introduction Neuromyelitis optica spectrum disorders (NMOSD) would disproportionately affect blacks within mixed populations. However, they are rarely reported in black African. The objective of this work was to report the experience of Togo, a West African country in terms of NMOSD. Methods This is a series of six cases diagnosed between 2015 and 2020 in the only three neurology departments in Togo. The diagnosis of NMOSD was made according to the criteria of the International Panel for NMO Diagnosis (2015) and the patients had a minimum clinical follow-up of 6 months after the diagnosis. The search for anti-aquaporin 4 (AQP4) antibodies was performed by immunofluorescence on transfected cells. Results The mean age was 25.33 years and the sex ratio female/male was 5/1. The average time between the first attack and the diagnosis was 122.83 days. Clinically, there was isolated medullary involvement (2/6), simultaneous opticomedullary involvement (3/6), and area postrema syndrome (1/6). Five patients were anti-AQP4 positive. All six patients had extensive longitudinal myelitis. At 6 months of follow-up, there was one case of death and one case of blindness. Conclusion The rarity of NMOSD cases in Togo could be linked to an underestimation. To better characterize the NMOSDs of the black African population, multicenter and multidisciplinary studies are necessary.

Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report

BackgroundSince the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention.Case presentationWe present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer–BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient’s symptoms.ConclusionsPathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.