Clinical and radiographic features of a cohort of adult and pediatric subjects in the Pacific Northwest with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly described clinical entity comprised of isolated or recurrent attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, or seronegative NMOSD. Prior studies report that 30-80 % of children and adults with MOGAD go on to have relapses though there are no reliable predictors. The objectives of this study were to (1) describe the demographic, clinical, and radiographic patterns of MOGAD at our center and (2) identify possible predictors of relapsing disease. METHODS: Single-center retrospective cohort study of pediatric and adult subjects with MOGAD evaluated at least once at our center between January 1, 2017 and September 30, 2022. Eligible subjects had a history of positive MOG-IgG and consistent clinical syndrome comprised of an initial attack of optic neuritis (ON), transverse myelitis (TM), ADEM, cerebral cortical encephalitis, seronegative neuromyelitis optica (simultaneous ON and TM), isolated brainstem or cerebellar syndrome, or other (not fitting into another group). Relapsing subjects or those remaining monophasic at 12 months were included in the analyses of predictors of relapsing disease. Covariates included age, sex, race/ethnicity, and index event phenotype. Unadjusted and adjusted risk ratios were calculated for pediatric and adult subjects. RESULTS: We describe the demographic, clinical, and radiographic characteristics of 58 subjects with MOGAD. Covariates from 48 subjects were analyzed for predictors of relapsing disease. In adults, Hispanics and non-White non-Hispanics were at increased risk of relapsing disease compared to non-Hispanic Whites [Adjusted RR 1.52 (95 % CI: 1.01, 2.30)]. There were no significant associations in the pediatric group. CONCLUSION: This study is the first to describe a cohort of MOGAD in the Pacific Northwest. Our findings highlight racial and ethnic differences in risk of relapsing MOGAD in adults. Further studies on racial and ethnic differences in MOGAD are needed to confirm these findings.

Transverse Myelitis Following SARS-CoV-2 Vaccination: A Pharmacoepidemiological Study in the World Health Organization's Database.

BACKGROUND: Transverse myelitis (TM) has recently been associated by health authorities with Ad26.COV2.S (Janssen/Johnson & Johnson), one of the 5 US Food and Drug Administration (FDA) or European Medicines Agency (EMA) labeled severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. It is unknown whether a similar association exists for the other FDA or EMA labeled SARS-CoV-2 vaccines (BNT162b2 [Pfizer/BioNTech], mRNA-1273 [Moderna], ChAdOx1nCov-19 [Oxford-AstraZeneca], and NVX-CoV2373 [Novavax]). This study aimed to evaluate the association between SARS-CoV-2 vaccine class and TM. METHODS: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from VigiBase, the World Health Organization's pharmacovigilance database. We first conducted a disproportionality analysis with the information component (IC) using the reports of TM that occurred within 28 days following exposure to the FDA or EMA labeled SARS-CoV-2 vaccines, from December 1, 2020 (first adverse event related to a SARS-CoV-2 vaccine) to March 27, 2022. Second, we analyzed the clinical features of SARS-CoV-2 vaccine-associated TM cases reported in VigiBase. RESULTS: TM was significantly associated both with the messenger ribonucleic acid (mRNA)-based (n = 364; IC025  = 0.62) and vector-based (n = 136; IC025  = 0.52) SARS-CoV-2 vaccines that are authorized by the FDA or the EMA. CONCLUSIONS: Findings from this observational, cross-sectional pharmacovigilance study showed that mRNA-based and vector-based FDA/EMA labeled SARS-CoV-2 vaccines can be associated with TM. However, because TM remains a rare event, with a previously reported rate of 0.28 cases per 1 million vaccine doses, the risk-benefit ratio in favor of vaccination against SARS-CoV-2 virus remains unchallenged. Rather, this study suggests that clinicians should consider the diagnosis of TM in patients presenting with early signs of spinal cord dysfunction after SARS-CoV-2 vaccination. ANN NEUROL 2022;92:1080-1089.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance.

BACKGROUND: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of 11 adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. METHODS: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bell's palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barré syndrome, transverse myelitis, acute myocardial infarction, and anaphylaxis during five pre-pandemic years (2015-2019) and 2020. RESULTS: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 191 for acute myocardial infarction, 43.9 for idiopathic thrombocytopenia, 28.8 for anaphylaxis, 27.8 for Bell's palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.7 for pericarditis, 2.9 for myocarditis, 2.0 for Kawasaki disease, 1.9 for Guillain-Barré syndrome, and 1.7 for transverse myelitis. Females had higher rates of acute disseminated encephalomyelitis, transverse myelitis and anaphylaxis while males had higher rates of myocarditis, pericarditis, and Guillain-Barré syndrome. Bell's palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12 to 59 years for myocarditis and ≥12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. CONCLUSIONS: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Seroprevalence of MOG and AQP4 Antibodies and Outcomes in an Indian Cohort of Pediatric Acquired Demyelinating Syndromes.

This study aimed to determine the seropositivity of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-4 antibodies (AQP4-Ab) and outcomes in children with acquired demyelinating syndromes (ADSs). Children (6 months-15 years) with suspected ADS were enrolled and tested for MOG-Ab and AQP4-Ab prospectively over 18 months at a tertiary care hospital in North India. Children with proven nonimmune-mediated neurological disorders were enrolled as controls. Of 79 children with suspected ADS, 66 were enrolled. Among the enrolled children with ADS, acute demyelinating encephalomyelitis (ADEM) (25) was the most common first clinical event followed by optic neuritis (ON) (20) and transverse myelitis (TM) (19; one child had ON and TM simultaneously [neuromyelitis optica spectrum disorders [NMOSDs]]), while two children had clinically isolated syndrome (CIS) apart from ON and TM. Fourteen (21.2%, confidence interval [CI] 11.3-31.1) tested positive for one antibody (12 [18.1%; 95% CI 10.5-25.5%] for MOG-Ab and 2 [3%; 95% CI 0-7.2%] for AQP4-Ab). None of the 62 controls tested positive for any antibody. The final diagnosis in those with the monophasic ADS was ADEM (21), ON (13), TM (16), and other CIS (1) while that in children with recurrent events was multiphasic disseminated encephalomyelitis (MDEM) (2), NMOSD (3), ADEM-ON (4), recurrent ON (4), and MS (2). Among those with the first event, 4/51 (7.8%; 95% CI 0.5-15.2%) were MOG-Ab positive and 2 AQP4-Ab positive, whereas 8/15 (53.3% [95% CI 28.1-78.6%]) with recurrent events (MDEM [2], ADEM-ON [4], recurrent ON [1], and recurrent TM [1]) were MOG-Ab positive. Hence, MOG-Abs are the most common antibodies detected in one in five children with pediatric ADS, especially in relapsing disease. AQP4-Abs are rare in children with ADS.

Association between covid-19 vaccination, SARS-CoV-2 infection, and risk of immune mediated neurological events: population based cohort and self-controlled case series analysis.

OBJECTIVE: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events. DESIGN: Population based historical rate comparison study and self-controlled case series analysis. SETTING: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data. PARTICIPANTS: 8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population. MAIN OUTCOME MEASURES: Outcomes were incidence of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test result for SARS-CoV-2, and between 2017 and 2019 for background rates in the general population cohort. Indirectly standardised incidence ratios were estimated. Adjusted incidence rate ratios were estimated from the self-controlled case series. RESULTS: The study included 4 376 535 people who received ChAdOx1 nCoV-19, 3 588 318 who received BNT162b2, 244 913 who received mRNA-1273, and 120 731 who received Ad26.CoV.2; 735 870 people with SARS-CoV-2 infection; and 14 330 080 people from the general population. Overall, post-vaccine rates were consistent with expected (background) rates for Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome. Self-controlled case series was conducted only for Bell's palsy, given limited statistical power, but with no safety signal seen for those vaccinated. Rates were, however, higher than expected after SARS-CoV-2 infection. For example, in the data from the UK, the standardised incidence ratio for Bell's palsy was 1.33 (1.02 to 1.74), for encephalomyelitis was 6.89 (3.82 to 12.44), and for Guillain-Barré syndrome was 3.53 (1.83 to 6.77). Transverse myelitis was rare (<5 events in all vaccinated cohorts) and could not be analysed. CONCLUSIONS: No safety signal was observed between covid-19 vaccines and the immune mediated neurological events of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. An increased risk of Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome was, however, observed for people with SARS-CoV-2 infection.

Late-onset neuromyelitis optica spectrum disorder: A case series from Iran.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune disease of the central nervous system that can start at ages of 50 or more, when it is called late-onset NMOSD (LO-NMOSD). Data on this disorder are sparse. In this cross-sectional study, patient characteristics of the disease were studied. LO-NMOSD patients of a tertiary center in Tehran were studied from 2016 to 2020. CASE REPORTS: Eight patients were identified, half of whom were men. The diagnostic delay was from no time-lapse to three years (mean: 0.62, SD: 1.06), which was significantly shorter than in early-onset patients. Seven patients (87.5%) tested positive for AQP4-IgG which was significantly higher compared to early-onset patients (p-value=0.01). Four patients (50%) had both transverse myelitis and optic neuritis as presenting symptoms, while three (38%) had just myelitis and only one (12%) had optic neuritis. CONCLUSION: There is discrepancy regarding different aspects of LO-NMOSD. Further studies are needed to clarify the subject in order to enhance diagnosis and treatment.

Relapse rates and risk factors for unfavorable neurological prognosis of transverse myelitis in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Transverse myelitis (TM) is a rare but severe systemic lupus erythematosus (SLE) manifestation. To date, the prognostic factors for SLE-associated TM have been far less well-studied. There are also controversial data on the association of antiphospholipid antibodies (aPLs), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, longitudinal extensive transverse myelitis (LETM), and decreased complement levels with the outcome of TM. We aimed to review the potential prognostic factors and integrate relapse rates of observational studies for SLE-associated TM. METHOD: To review the prognosis for SLE-associated TM, relevant articles published up to July 30, 2021, were comprehensively and systematically identified from PubMed, EMBASE and Web of Science databases. Five studies encompassing 283 patients with SLE-related TM were included in this meta-analysis; raw data were obtained from three studies. RESULTS: The risk factors for unfavorable neurological outcome included demographic features, clinical characteristics, laboratory data, among which a grade of A, B or C on the American Spinal Injury Association Impairment Scale (AIS) at the onset of TM was associated with poor prognosis (OR: 56.05, 95% CI: 6.29-499.25, P < 0.001). The presence of hypoglycorrhachia was also correlated with a worse prognosis (OR: 10.78, 95% CI: 3.74-31.07, P < 0.001). No noticeable correlation was revealed between a poor outcome and positive aPLs and different aPLs profiles (anticardiolipin antibody [aCL], anti-ß2-glycoprotein I (anti-ß2GPI], lupus anticoagulant [LA]). The pooled 1-, 3- and 5-year relapse rates were 22% (95% CI: 0.13-0.31), 34% (95% CI: 0.22-0.47) and 36% (95% CI: 0.14-0.58), respectively. No significant publication bias was found. CONCLUSION: A grade of A, B, or C on the AIS at initial TM and the presence of hypoglycorrhachia were found to be related to a worse prognosis in patients with SLE-associated TM. Notably, aPLs and different aPLs profiles may not suggest poor neurological outcome. The long-term relapse rate of patients with SLE-associated TM was relatively high. We recommend that treatment be stratified based on the initial severity of myelitis. For patients with severe myelitis, early intensive therapy may be initiated as soon as possible.

Demographic and clinical characteristics of patients with transverse myelitis and traumatic spinal cord injury: A comparative retrospective study.

OBJECTIVES: To identify the demographic and clinical characteristics of patients with transverse myelitis (TM) and to compare functional status between those patients and a matched group with traumatic spinal cord injury (T-SCI). STUDY DESIGN: Retrospective study. SETTING: A tertiary rehabilitation hospital. PARTICIPANTS: The demographic and clinical characteristics of 484 T-SCI patients and 25 TM patients were compared. Functional status was further analyzed by matching the two groups. OUTCOME MEASUREMENTS: The matched patients were compared in terms of motor and sensory functions, bladder and bowel symptoms, ambulation level, the Rivermead Mobility Index, and SCI-related medical complications. RESULTS: The mean age of the TM patients was 35.6 years and was similar to that of the T-SCI patients. There were significantly more females in the TM group (P = 0.017). Individuals with TM had fewer cervical injuries (P = 0.032) and a higher rate of paraplegia (P = 0.047) and were more often incomplete (P = 0.009) than those with T-SCI. Sensory function was significantly better in the TM group compared to the matched T-SCI group (P = 0.05). Independent ambulation frequency was higher in the TM patients. The SCI-related complications seen in the TM group were as common as those in the T-SCI group. CONCLUSION: The TM and T-SCI groups differed in terms of the demographic and clinical characteristics recorded. Additionally, when matched for these differences, functional status was slightly better in the TM group. However, like T-SCI, TM was a significant cause of disability and SCI-related complications were common.

Modern Look at Transverse Myelitis and Inflammatory Myelopathy: Epidemiology of the National Veterans Health Administration Population.

BACKGROUND AND OBJECTIVES: To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA). METHODS: This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria. RESULTS: We identified 4,084 patients with an International Classification of Diseases (ICD) code consistent with TM and confirmed the diagnosis in 1,001 individuals (90.7% males, median age 64.2, 67.7% Caucasian, and 31.4% smokers). The point prevalence was 7.86 cases per 100,000 people. Less than half of the cohort underwent a lumbar puncture, whereas only 31.8% had a final, disease-associated TM diagnosis. The median mRS score at symptom onset was 3 (interquartile range 2-4), which remained unchanged at follow-up, although less than half (43.2%) of the patients received corticosteroids, IVIg, or plasma exchange. Approximately one-quarter of patients (24.3%) had longitudinal extensive TM, which was associated with poorer outcomes (p = 0.002). A total of 108 patients (10.8%) died during our review (94.4% males, median age 66.5%, and 70.4% Caucasian). Mortality was associated with a higher mRS score at follow-up (OR 1.94, 95% CI, 1.57-2.40) and tobacco use (OR 1.87, 95% CI, 1.17-2.99). DISCUSSION: This national TM review highlights the relatively high prevalence of TM in a modern cohort. It also underscores the importance of a precise and thorough workup in this disabling disorder to ensure diagnostic precision and ensure optimal management for patients with TM in the future.

Transverse Myelitis in Systemic Lupus Erythematosus: Clinical Features and Prognostic Factors in a Large Cohort of Latin American Patients.

BACKGROUND: Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM. METHODS: In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS). RESULTS: Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse. CONCLUSIONS: Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors.

Spectrum of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases: an Indian perspective.

Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is involved in the pathogenesis of central nervous system (CNS) demyelination disorders. We aimed to explore the spectrum of MOG-Ab-associated diseases in eastern India. A single-center, prospective observational study was done over a period of 2 years in a tertiary care hospital of eastern India. Patients with CNS demyelination disorders who tested positive for MOG-Ab using live cell-based assay were included in the study; while, those with age less than 1 year, documented preexisting CNS structural lesions, developmental delays or diagnosed multiple sclerosis were excluded. Demographic profile, clinical spectrum, disease course, radiological features as well as response to treatment were analyzed among included patients. Twenty MOG-Ab-positive patients were included (M:F 1:1.85). The median age of symptom onset was 10.5 years. The median follow-up of patients was 13 months. Acute disseminated encephalomyelitis (ADEM) was the commonest presentation at first attack (55%), followed by optic neuritis (ON) (45%). Patients with ADEM had a significantly lower age at first attack (p = 0.025). Monophasic and relapsing disease courses were seen in 45% and 55% patients, respectively. While all patients with only ADEM had a monophasic course, 77.8% with ON had a relapsing course. Among patients who presented with isolated transverse myelitis, 75% had a monophasic course and all had disease confined to the spinal cord. Good response to corticosteroids was seen in majority of participants. Second-line drugs were needed in 55% patients, rituximab being the commonest second-line agent used. 35% patients had significant disability (EDSS > 4) at last follow-up. MOG-Ab-associated diseases have diverse clinical phenotypes characterized by age-dependent pattern-specific courses.

Frequency and etiology of acute transverse myelitis in Southern Finland.

OBJECTIVE: Acute transverse myelitis is a relatively rare, frequently debilitating but potentially treatable emergency. The objective of this study was to evaluate the incidence and etiology of acute transverse myelitis in two major hospital districts in Southern Finland. METHODS: We identified all patients with acute transverse myelitis admitted to Turku University Hospital and Päijät-Häme Central hospital during nine years. The two hospitals serve a catchment area of 673,000 people in Southern Finland. Acute transverse myelitis was diagnosed according to the 2002 Transverse Myelitis Consortium Working Group. Patient files were reviewed for details of the clinical presentation and disease outcome, for laboratory findings and for neuroimaging. Charts were re-evaluated after an average of 7.7 years for confirmation of the acute transverse myelitis etiology. RESULTS: In total 63 patients fulfilled the Transverse Myelitis Consortium Working Group diagnostic criteria for acute transverse myelitis. The frequency of the condition was hence 1.04 cases/ 100,000 inhabitants/ year. In the studied cohort, 7/63 (11%) patients had idiopathic transverse myelitis after initial evaluation and in 4/63 (6.3%) patients the idiopathic transverse myelitis remained the final diagnosis after follow-up and re-evaluation. Of the disease-associated myelitis cases MS or clinically isolated syndrome was the largest group, explaining 41% of all myelitis cases. The mean follow-up time before a patient was diagnosed with MS was 1.7 ± 2.2 years. Other etiologies included acute disseminated encephalomyelitis (ADEM), neurosarcoidosis, neuromyelitis optica (NMO), systemic autoimmune diseases and infectious diseases. CONCLUSIONS: In more than half of the acute transverse myelitis cases the final diagnosis is other than MS. Careful diagnostic work-up is needed for correct early treatment and best long-term outcome.

The frequency of longitudinally extensive transverse myelitis in MS: A population-based study.

BACKGROUND: Determining the frequency of longitudinally-extensive transverse myelitis (LETM: T2-lesion ≥3 vertebral segments) in multiple sclerosis (MS) is essential to assess its utility in differentiating from aquaporin-4-IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD) and myelin-oligodendrocyte-glycoprotein-IgG (MOG-IgG) myelitis. We sought to determine the frequency of LETM in MS during a myelitis attack. METHODS: We identified Olmsted County (MN, USA) residents on 12/31/2011 with inflammatory demyelinating disease. Inclusion criteria were: 1) Clinical myelitis episode accompanied by a new spinal magnetic resonance imaging (MRI) lesion (≤6 weeks from onset); 2) MS diagnosis by 2010 McDonald criteria; 3) Seronegative for AQP4-IgG and MOG-IgG. MRI characteristics were determined. RESULTS: Sixty-seven patients (median age at myelitis: 41 years [range, 16-65]; 76% females) with 92 myelitis attacks accompanied by a new MRI spinal cord lesion were identified. The frequency of LETM was 0%. The median T2-hyperintense lesion length in vertebral segments was 1.0 (range, 0.5-2.5) and 82/92 (89%) were peripheral in location on axial sequences; 58% had associated gadolinium enhancement. Two patients (2% of attacks) had multiple short lesions resembling LETM on sagittal images but axial sequences confirmed multiple non-contiguous short lesions. CONCLUSION: LETM is rare in adult MS myelitis and its presence should prompt evaluation for AQP4-IgG, MOG-IgG or other etiologies. Careful scrutiny of axial images is important as coalescence of multiple short lesions may lead to the artifactual appearance of an LETM.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder and systemic autoimmune diseases overlap syndrome: a single-center experience.

OBJECTIVE: To describe the clinical and radiological characteristics and outcomes of patients with aquaporin-4-immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) coexisting with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) in a single center. METHODS: We included patients with diagnosis of NMOSD and a concomitant diagnosis of SLE or pSS. Demographic, clinical, serological and imaging characteristics were retrieved from clinical charts. RESULTS: Twelve patients were included, of whom 11 (91.7%) were women. Seven (58.3%) had SLE and five (41.7%) pSS. In five (41.7%) patients NMOSD followed SLE/pSS onset, four (33.3%) patients had a simultaneous presentation, and in three (25%) NMOSD preceded pSS onset. The mean age at first neurological event was 39 years. Eleven patients (91.7%) experienced acute transverse myelitis/longitudinally extensive transverse myelitis, five (41.7%) optic neuritis, three (25%) a cerebral syndrome and two (16.7%) each area postrema syndrome, acute brainstem syndrome and cerebellar syndrome. Eleven (91.7%) patients went into either total or partial NMOSD remission at median follow-up of 89.5 months. CONCLUSION: AQP4-IgG seropositive NMOSD arose in the context of quiescent SLE and pSS with extraglandular features. As NMOSD coexisting with SLE/pSS is rare, collaborative multicenter studies are needed to clarify the natural history and outcomes of this overlap syndrome.

Higher health care use before a clinically isolated syndrome with or without subsequent MS.

BACKGROUND: To establish whether a unique multiple sclerosis (MS) prodrome exists by comparing health care utilization in the five-year period before initial presentation with optic neuritis (ON) or transverse myelitis (TM) among those who were and were not subsequently diagnosed with MS. METHODS: Using population-based administrative health data we conducted a retrospective cohort study in three Canadian provinces. We identified individuals with a clinically isolated syndrome (ON or TM), who were eventually diagnosed with MS (CIS-MS) or not (CIS-non MS), and a control cohort matched on age, sex and region without a CIS. We compared rates of hospitalization, physician services use and prescription drug use in the five years before the first ON or TM claim (labeled years -1,-2,-3,-4,-5) using negative binomial regression models adjusted for age, sex, socioeconomic status and index year. RESULTS: We identified 1,155 CIS-MS cases, 20,638 CIS-non MS cases, and 108,726 matched controls. Compared to matched controls, the CIS-MS cohort had a higher hospitalization rate (years -5 and -1), physician visits (all years) and prescription drug use (years -4 and -1). Compared to matched controls, the CIS-non MS cohort had a higher rate of hospitalizations (all years), physician visits (all years) and prescription drug use (all years). CONCLUSION: Health care use was higher in individuals with a CIS than without a CIS in the five years before an incident demyelinating event, regardless of whether they were subsequently diagnosed with MS. This suggests that there is a prodromal period before CIS which is not unique to MS.

Aquaporin-4 and MOG autoantibody discovery in idiopathic transverse myelitis epidemiology.

OBJECTIVE: Diagnostic criteria from 2002 classify transverse myelitis (TM) as idiopathic or disease associated but predate the discovery of aquaporin-4 (AQP4)-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which associate with TM. Prior incidence estimates of idiopathic TM (ITM) range from 1 to 6.2 per 1 million. We sought to determine whether the population-based incidence and prevalence of ITM were reduced by testing patients with ITM for AQP4/MOG-IgG and reclassifying seropositive cases as having disease-associated TM. METHODS: For this observational study, we retrospectively identified all cases of incident (January 1, 2003-December 31, 2016) and prevalent (December 31, 2016) ITM in Olmsted County (85% white) by using the Rochester Epidemiology Project medical records linkage system. ITM was defined by the 2002 Transverse MyelitisConsortium Working Group diagnostic criteria. Available sera were tested for AQP4-IgG and MOG-IgG. RESULTS: Twenty-four patients (incident 22, prevalent 17) initially met 2002 ITM criteria (longitudinally extensive TM [LETM] 6). Sera were tested for AQP4-IgG in 22 of 24 (92%) and MOG-IgG in 21 of 24 (88%). Three seropositive cases (AQP4-IgG 2, MOG-IgG 1) were identified and reclassified as having disease-associated TM, accounting for 14% of total incident and 12% of total prevalent cases. AQP4-IgG and MOG-IgG seropositive cases represented 50% (3 of 6) of idiopathic LETM. After reclassification of seropositive patients, the final ITM incidence was 8.6 per 1,000,000 and prevalence was 7.9 per 100,000. Three cases of ITM (14%) subsequently fulfilled multiple sclerosis criteria within the study period. CONCLUSIONS: The availability of AQP4-IgG and MOG-IgG modestly reduced ITM incidence and prevalence, which remained higher than previously reported in this predominantly white population. Incorporation of these biomarkers into future revisions of TM diagnostic criteria should be considered.

New onset transverse myelitis diagnostic accuracy and patient experiences.

IMPORTANCE: Patients afflicted with rare diseases often have a delay in diagnosis and treatment. Understanding the prevalence and impact of delayed diagnosis in transverse myelitis could trigger directed educational initiatives to increase clinician awareness and improve care. OBJECTIVE: To determine if symptoms at onset or care provider initially approached was associated with time to diagnosis, treatment or outcome in patients with transverse myelitis. DESIGN: This was an online patient and caregiver standardized survey to collect data about the initial medical experience. Patients were recruited through social media to complete a survey about initial symptoms, care provider approached for diagnosis, first events (hospital admission, testing, sent home, etc.), first diagnosis, time to treatment and outcomes. The data was collected by an independent, non-profit patient advocacy organization (The Transverse Myelitis Association) and provided to researchers for analysis. SETTING: This was an online survey of a prevalent cohort of individuals diagnosis with transverse myelitis. PARTICIPANTS: Patients with various autoimmune disorders responded to the survey. These included patients with multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis and idiopathic transverse myelitis. Only data about patients, greater than a year of age, with a diagnosis of transverse myelitis were included in the study.

Identifying optic neuritis and transverse myelitis using administrative data.

OBJECTIVE: We aimed to validate administrative case definitions to identify individuals with optic neuritis (ON) or transverse myelitis (TM), and to distinguish which of these individuals had a monophasic presentation versus multiple sclerosis (MS). METHODS: Using population-based administrative (health claims) data from Manitoba, Canada, we developed case definitions for ON and TM, and distinguished individuals who had monophasic presentations (ON-nonMS, TM-nonMS) versus those later diagnosed with MS (ON-MS, TM-MS). We compared performance of these case definitions to diagnoses based on medical records review in a reference cohort (n = 1251) using sensitivity, specificity, positive predictive value and negative predictive value. We estimated the annual incidence of these conditions for a three-year period (2011-2013). RESULTS: When compared to medical records, using ≥1 physician visit, the case definition for ON had good sensitivity (88.5%), and specificity (82.7%) whereas the case definition for TM had low sensitivity (25.9%) and higher specificity (89.0%). Findings for the other case definitions tested were: ON-MS (sensitivity: 84.1%, specificity: 83.9%), ON-nonMS (sensitivity: 66.7%, specificity 98.5%), TM-MS (sensitivity: 22.2%, specificity: 90.4%), and TM-nonMS (sensitivity: 3.7%, specificity: 99.7%). After applying the ON and TM case definitions to administrative data, the average annual incidence of ON over the period 2011-2013 was 75.9 per 100,000 person-years (95%CI: 72.8, 79.1) and of TM was 18.3 per 100,000 person-years (95%CI: 16.8, 19.8). CONCLUSION: Administrative data can be used to identify individuals with incident ON and TM, and to distinguish those with monophasic syndromes from those with an incident presentation of MS.

Cardiovascular conditions in persons with multiple sclerosis, neuromyelitis optica and transverse myelitis.

BACKGROUND: Cardiovascular conditions are associated with poorer outcomes in multiple sclerosis (MS). Whether the burden of cardiovascular conditions differs between those with demyelinating disease and unaffected controls is not clear. The objective of this study is to investigate the burden and age of onset of cardiovascular conditions in a US population with MS, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis (TM) to unaffected controls adjusting for likely confounders. METHODS: Using a case-control study design, we compared the burden of self-reported diabetes mellitus type 2, heart disease, hyperlipidemia, and hypertension in cases with MS (N = 1,548), NMOSD (N = 306), and TM (N = 145) to controls (N = 677), adjusting for demographics, smoking history, obesity, family history of individual cardiovascular conditions, and presence of other cardiovascular conditions. The age of onset for individual cardiovascular conditions were also compared between cases and controls. RESULTS: MS cases were 48% more likely to have ever had hypertension than controls (p = 0.01). The prevalence of other cardiovascular conditions did not differ across cases and controls. There were also no differences in the age of cardiovascular disease onset between cases and controls. CONCLUSION: Cardiovascular conditions are as common in those with demyelinating diseases compared to unaffected individuals, with hypertension being more common among those with MS.