Criteria For Neuromyelitis Optica Spectrum Disorders Research Articles

Occurrence of area postrema syndrome during follow-up: phenotype and influence over NMOSD activity in LATAM in real-world settings.

We aimed to assess the frequency, duration, and severity of area postrema syndrome (APS) during follow-up in neuromyelitis optica spectrum disorder (NMOSD) patients, as well as its association with inflammatory activity and prognostic factors of APS severity in a real-world setting. We conducted a retrospective study on a cohort of Latin American (LATAM) NMOSD patients who had experienced APS during their follow-up. Patients from Mexico, Peru, Brazil, Colombia, Panama, Chile and Argentina patients who met 2015 NMOSD criteria were included. We evaluated data on symptom type (nausea, vomiting and/or hiccups), frequency, duration, severity (measured by APS severity scale), association with other NMOSD core relapses, and acute treatments (symptomatic and immunotherapy or plasmapheresis). Logistic regression was conducted to evaluate factors associated with APS severity (vs. mild-moderate). Out of 631 NMOSD patients, 116 (18.3%) developed APS during their follow-up. The most common APS phenotype was severe. Inflammatory activity (i.e., relapses) significantly decreased after the onset of APS. Half of the patients experienced isolated APS with a median duration of 10days, and the most frequently used acute treatment was IV steroids. All three symptoms were present in 44.6% of the patients. APS symptoms resolved following immunotherapy. Logistic regression did not identify independent factors associated with the severity of APS. Our findings indicate that 18.3% of NMOSD patients developed APS during the follow-up period, with most patients fulfilling criteria for severe APS. The inflammatory activity decreased after the onset of APS compared to the previous year.

Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder

Background and objectives Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. Methods Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. Results 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. Conclusion It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

Rituximab De-escalation in Patients With Neuromyelitis Optica Spectrum Disorder.

Exit strategies such as de-escalations have not been evaluated for rituximab in patients with neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that they are associated with disease reactivations and aimed to estimate this risk. We describe a case series of real-world de-escalations from the French NMOSD registry (NOMADMUS). All patients met the 2015 IPND diagnostic criteria for NMOSD. A computerized screening of the registry extracted patients with rituximab de-escalations and at least 12 months of subsequent follow-up. We searched for 7 de-escalation regimens: scheduled discontinuations or switches to an oral treatment after single infusion cycles, scheduled discontinuations or switches to an oral treatment after periodic infusions, de-escalations before pregnancies, de-escalations after tolerance issues, and increased infusion intervals. Rituximab discontinuations motivated by inefficacy or for unknown purposes were excluded. The primary outcome was the absolute risk of NMOSD reactivation (one or more relapses) at 12 months. AQP4+ and AQP4- serotypes were analyzed separately. We identified 137 rituximab de-escalations between 2006 and 2019 that corresponded to a predefined group: 13 discontinuations after a single infusion cycle, 6 switches to an oral treatment after a single infusion cycle, 9 discontinuations after periodic infusions, 5 switches to an oral treatment after periodic infusions, 4 de-escalations before pregnancies, 9 de-escalations after tolerance issues, and 91 increased infusion intervals. No group remained relapse-free over the whole de-escalation follow-up (mean: 3.2 years; range: 0.79 - 9.5), except pregnancies in AQP+ patients. In all groups combined, and within 12 months, reactivations occurred after 11/119 de-escalations in patients with AQP4+ NMOSD (9.2%, CI95% [4.7; 15.9]), from 0.69 to 10.0 months, and in 5/18 de-escalations in patients with AQP4- NMOSD (27.8%, CI95% [9.7; 53.5]), from 1.1 to 9.9 months. There is a risk of NMOSD reactivation whatever the rituximab de-escalation regimen. Registered on ClinicalTrials.gov: NCT02850705. This study provides Class IV evidence that de-escalation of rituximab increases the probability of disease reactivation.

Most Opticospinal Demyelination is NMOSD, not MS-A 17-year UK Longitudinal Cohort Study (P5-3.003)

<h3>Objective:</h3> To evaluate clinical outcomes in a cohort of patients with Opticospinal Demyelination (OSD). <h3>Background:</h3> Classification of central nervous system inflammation has progressed with the identification of aquaporin-4 (AQP4) antibodies in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibodies in MOG antibody disease (MOGAD) in addition to multiple sclerosis (MS). However, as defined in 2003, patients with opticospinal demyelination (optic neuritis (ON), short-segment transverse myelitis (TM), and brain imaging not supportive of MS) do not fulfil internationally approved criteria for MS, NMOSD, or MOGAD. <h3>Design/Methods:</h3> Between 2003–2005, 128 cases of OSD were reported via the British Neurological Surveillance Unit. In 2011, 2015 and 2022 patients and physicians were contacted for clinical, radiological, and serological (e.g., AQP4-IgG and MOG-IgG) data as part of a prospective longitudinal cohort study. <h3>Results:</h3> Of 128 cases, 67 (52%) patients fulfilled OSD diagnostic criteria. At 17 years 39/60 patients (65%) now met NMOSD diagnostic criteria, 14 (23%) had MS and 7 (12%) had OSD. The median time to diagnosis of NMOSD was 107 months (85–261) and to MS was 189 months (79–346). The median age of OSD patients at onset was 37 (25–48) years and 5/7 were male. A relapsing course was observed in 6/7 patients with a median annualised relapse rate of 0.22 (0.13–0.49). At last follow-up the median EDSS was 2.5 (range; 1–6.5) and only 2/7 patients had an EDSS&gt;3.5. <h3>Conclusions:</h3> OSD is diagnostically distinct from MS, NMOSD, and MOGAD. However, after 2 decades most OSD patients reached a diagnosis of NMOSD or MS, so OSD may lie on a spectrum with these conditions. Of the 12% of cases that retained OSD classification, all but 1 had a relapsing course but rates of significant disability were low. Future studies should focus on characterising diagnostic and prognostic biomarkers in this unique subtype of non-MS CNS inflammation. <b>Disclosure:</b> Dr. Forcadela has nothing to disclose. Dr. Rocchi has nothing to disclose. Dr. Panicker has nothing to disclose. Kerry Mutch has nothing to disclose. Dr. Huda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. Dr. Jacob has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ALEXION. Dr. Hamid has nothing to disclose.

Factors associated with the misdiagnosis of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition that is associated with severe disability. Approximately 40% of individuals are misdiagnosed with multiple sclerosis (MS) or other diseases. We aimed to define factors that influence the misdiagnosis of people with NMOSD and provide strategies for reducing error rates. A retrospective study was performed involving all people with a confirmed diagnosis of NMOSD within a single academic institution. Comprehensive clinical timelines were constructed for each individual that included presenting symptoms, provider type and timing of evaluations, aquaporin 4-IgG (AQP4) results, and MRI scans. Two-sample comparisons of continuous and categorial variables were performed for people accurately diagnosed with NMOSD and those originally misdiagnosed with another medical condition. A subanalysis of only AQP4-IgG positive people was also performed. The study cohort included 199 people fulfilling International Panel criteria for NMOSD with 71 people (62 female; mean age at first symptom presentation (standard deviation (SD))=32.8 years (y) (SD 16.1)) being initially misdiagnosed and 128 people (106 female; 41.14y (SD 15.41)) who were accurately diagnosed. Of the 199 people with NMOSD, 166 had a positive serostatus. Identified factors associated with misdiagnosis, regardless of AQP4-IgG serostatus, were the presence of protracted nausea/vomiting/hiccups without any accompanying neurological symptoms, 23 (32.4%) versus 16 (12.5%) (p=0.001), a longer median (range) time to see a neuroimmunology specialist 4.2y (0.14-31.8) versus 0.5y (0.0-21.2) (p<0.0001), and a delay in acquiring an MRI study, 4.7y (0.0-27.3) versus 0.3y (0.0-20.2) (p<0.0001). A greater proportion of people misdiagnosed were identified with a negative live-cell based AQP4-IgG serum test result, 13/13 (100%) versus 22/114 (19.3%) (p<0.0001). Additionally, the mean (SD) time between a first negative and successive live-cell based AQP4-IgG positive test result was greater for people misdiagnosed with another condition, 3.9y (SD 5.0) versus 1.5y (SD 2.1) (p=0.01). Although not significant between groups, a rash was also reported in 63/199 people with NMOSD, with 31/63 having an anti-nuclear antibody titer ≥ 1:160. Defined factors can help guide both generalists and specialists in the pursuit of strategies aimed at efficiently diagnosing those with NMOSD such that effective care can be delivered.

Rare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are rare, debilitating autoimmune diseases of the central nervous system. Many NMOSD patients have antibodies to Aquaporin-4 (AQP4). Prior studies show associations of NMOSD with individual Human Leukocyte Antigen (HLA) alleles and with mutations in the complement pathway and potassium channels. HLA allele associations with NMOSD are inconsistent between populations, suggesting complex relationships between the identified alleles and risk of disease. We used a retrospective case-control approach to identify contributing genetic variants in patients who met the diagnostic criteria for NMOSD and their unaffected family members. Potentially deleterious variants identified in NMOSD patients were compared to members of their families who do not have the disease and to existing databases of human genetic variation. HLA sequences from patients from Belgrade, Serbia, were compared to the frequency of HLA haplotypes in the general population in Belgrade. We analyzed exome sequencing on 40 NMOSD patients and identified rare inherited variants in the complement pathway and potassium channel genes. Haplotype analysis further detected two haplotypes, HLA-A*01, B*08, DRB1*03 and HLA-A*01, B*08, C*07, DRB1*03, DQB1*02, which were more prevalent in NMOSD patients than in unaffected individuals. In silico modeling indicates that HLA molecules within these haplotypes are predicted to bind AQP4 at several sites, potentially contributing to the development of autoimmunity. Our results point to possible autoimmune and neurodegenerative mechanisms that cause NMOSD, and can be used to investigate potential NMOSD drug targets.

Pediatric Neuromyelitis Optica Spectrum Disorder Presenting as Intractable Vomiting

Pediatric neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that affects the central nervous system. Common presentations include weakness and sensory changes secondary to transverse myelitis, or vision loss due to optic neuritis. Area postrema syndrome, characterized by intractable nausea, vomiting, or hiccups secondary to a demyelinating lesion in the chemoreceptor trigger zone, is part of the core diagnostic criteria for NMOSD. However, it has infrequently been described as an initial presentation of pediatric NMOSD. Here, we present the case of a 13-year-old female who presented with intractable vomiting, which was initially presumed to be secondary to gastrointestinal pathology. It was not until she developed transverse myelitis that the etiology of her intractable vomiting was identified as area postrema syndrome secondary to NMOSD. She was successfully treated with rituximab, and she remains relapse-free after the initiation of immunosuppressive therapy. This case highlights this rare presentation of NMOSD and emphasizes the need for increased awareness amongst pediatric providers in recognizing this diagnosis and preventing delays in treatment. Int J Clin Pediatr. 2022;11(2):35-38 doi: https://doi.org/10.14740/ijcp478

Epidemiology of neuromyelitis optica spectrum. New and old challenges

This epidemiological review on neuromyelitis optica spectrum disorder (NMOSD) focuses on describing the methodologies employed in studies conducted under the 2015 NMOSD criteria and the studies conducted in Spain and Latin America, as well as examining factors related to the prognosis of the disease. The methodology used in the studies varies essentially in the application of different diagnostic criteria, sources of records, antibody detection techniques and standardisation methods. However, in general terms, NMOSD is distributed worldwide with an incidence/prevalence that is higher in women than in men, and in Asian and African-American countries than in Western countries. The frequency increases in parallel to age, with a peak incidence/prevalence in the 40-59 age range. The Latin American population has particular epidemiological characteristics linked to its racial and genetic mix. Finally, epidemiological variables, such as belonging to the black race, being of older age at onset and being female, are associated with a worse functional prognosis. Epidemiological data on NMOSD vary from one study to another, largely due to discrepancies in the methodological designs. Although Latin American studies are scarce, the findings described are associated with their ethnic mix. The homogenisation of criteria and the use of similar diagnostic techniques and standardisation methods must be implemented for the correct study of the epidemiology of NMOSD.

Treatment response, risk of relapse and clinical characteristics of Taiwanese patients with neuromyelitis optica spectrum disorder

The long-term disease course and efficacy of maintenance therapies have rarely been investigated in Asian patients with neuromyelitis optica spectrum disorder (NMOSD). Medical records of patients fulfilling the 2015 International Consensus Diagnostic Criteria for NMOSD at three medical centers in Taiwan were systematically analyzed. Linear regression analysis was performed to investigate factors related to annualized relapse rate (ARR); survival analysis was used to estimate the relapse-free intervals among therapies. A total of 557 relapses affecting 648 regions (202 optic neuritis, 352 acute myelitis, and 94 brain syndromes) in 204 patients were analyzed during a follow-up period of 69.5 months (range, 1-420). Up to 36.1% of myelitis-onset patients and 24.0% of optic neuritis-onset patients exhibited a limited form disease, defined as having one or more relapses confined to the same region. The median ARR was significantly lower in patients with limited form disease than those with relapses involving multiple regions (0.30 vs. 0.47, respectively). An older age at disease onset was associated with a lower ARR (p=0.023). Kaplan-Meier analysis showed that the estimated time (months) to next relapse was longest in rituximab-treatment group (58.0±13.2), followed by immunosuppressant (48.5±4.8) or prednisone (29.6±4.6) groups, and shortest in those without maintenance therapy (27.6±4.2) (p=8.1×10-7). Limited form disease and older age at disease onset are associated with a lower relapse rate in NMOSD. Compared to no maintenance therapy, rituximab and immunosuppressant significantly reduce the relapse risks.

Diagnostic value of aquaporin-4-IgG live cell based assay in neuromyelitis optica spectrum disorders.

ObjectiveDetermine the utility of aquaporin 4 IgG (AQP4-IgG) testing (live cell-based assay) for Neuromyelitis Optica Spectrum Disorders (NMOSD).MethodsWe included Mayo Clinic patients (1/1/2018-12/31/2019) tested for serum AQP4-IgG by live cell-based flow-cytometric assay. Medical records were reviewed to assess if patients fulfilled 2015 NMOSD criteria.ResultsOf 1371 patients tested, 41 were positive (3%) and all fulfilled NMOSD criteria with AQP4-IgG (specificity = 100%). Only 10/1330 testing negative met NMOSD criteria without AQP4-IgG (sensitivity = 80%) and seven of these 10 were MOG-IgG positive.ConclusionsAQP4-IgG by live cell-based assay was highly specific and without false positives in a high throughput setting.

Update on treatment of the other demyelinating diseases

Aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathic disease and severe attacks of NMOSD can quickly lead to blindness and paralysis. The international diagnostic criteria of NMOSD (2015) have facilitated early diagnosis of the disease which allows for early treatment. Some disease modifying drugs for multiple sclerosis are inefficacious and immunosuppressive drugs (corticosteroid, azathioprine, mycophenolate mofetil, etc) have been used to prevent relapse in AQP4-IgG-positive NMOSD. A few years ago, the results of randomized controlled trials of four monoclonal antibodies (anti-C5, anti-IL-6R, anti-CD19, and anti-CD20) in AQP4-IgG-positive NMOSD cases were reported and they are expected to change the therapeutic landscape. Efficacy, safety, tolerability, and practical considerations, including patient's life style and potential cost, are important in deciding on the therapeutic strategy. Other therapeutic approaches, such as stem cell transplantation and tolerance induction, may also be promising in this disease. AQP4-IgG-seronegative NMOSD is a diagnostic challenge and could be a heterogeneous group of diseases. Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) is a newly recognized entity with NMOSD and other clinical phenotypes. Some cases of MOGAD are relapsing. In addition to immunosuppressants used in AQP4-IgG-positve NMOSD, intravenous immunoglobulins appear to be efficacious in MOGAD. Overall, rituximab can reduce the relapse rate, but unlike AQP4-IgG-positive NMOSD, relapse may occur in some MOGAD patients receiving rituximab despite effective B cell depletion. In this presentation, the therapeutic issues and evidence of AQP4-IgG-positive NMOSD, AQP4-IgG-negative NMOSD including MOGAD will be reviewed and the challenges that lie ahead will be discussed.

Aquaporin-4 Autoantibody Detection by ELISA: A Retrospective Characterization of a Commonly Used Assay.

Objective Aquaporin-4 (AQP4) serum autoantibodies are detected by a variety of methods. The highest sensitivity is achieved with cell-based assays, but the enzyme-linked immunosorbent assay (ELISA) is still commonly utilized by clinicians worldwide. Methods We performed a retrospective review to identify all patients at the University of Utah who had AQP4 ELISA testing at ARUP Laboratories from 2010 to 2017. We then reviewed their diagnostic evaluation and final diagnosis based on the ELISA titer result. Results A total of 750 tests for the AQP4 ELISA were analyzed, and 47 unique patients with positive titers were identified. Less than half of these patients (49%) met the clinical criteria for neuromyelitis optica spectrum disorder (NMOSD). In cases of low positive titers (3.0–7.9 U/mL, n = 19), the most common final diagnosis was multiple sclerosis (52.6%). In the moderate positive cohort (8.0–79.9 U/mL, n = 14), only a little more than half the cohort (64.3%) had NMOSD. In cases with high positives (80–160 U/mL, n = 14), 100% of patients met clinical criteria for NMOSD. Conclusions Our data illustrates diagnostic uncertainty associated with the AQP4 ELISA, an assay that is still commonly ordered by clinicians despite the availability of more sensitive and specific tests to detect AQP4 autoantibodies in patients suspected of having NMOSD. In particular, low positive titer AQP4 ELISA results are particularly nonspecific for the diagnosis of NMOSD. The importance of accessibility to both sensitive and specific AQP4 testing cannot be overemphasized in clinical practice.

P-OT003. A case series of familial neuromyelitis optica spectrum disorder (NMOSD)

Introduction . Evidence of familial neuromyelitis optica spectrum disorder (NMOSD) have been limited, reported to comprised of 3% of total cases (Matiello et al., 2010). We report a case series of possible familial NMOSD involving only 1 generation, namely 3 out of the 6 female siblings. Results . All 3 patients were female Malaysian Chinese with age of disease onset of 39, 56, and 57 years respectively. Two of them demonstrated AQP4 seropositivity while one passed away without being tested. Their presenting features were optic neuritis (ON) plus transverse myelitis (TM) in Patient 1 and TM in both Patient 2 and Patient 3. Subsequent relapses involved both ON and TM over years. They demonstrated relapsing disease course with annualized relapse rates of 0.67, 0.55 and 0.20 respectively. Both Patient 2 and Patient 3 demonstrated longitudinally extensive transverse myelitis on spinal MRI with normal MRI brain. Apart from serum anti-Ro positivity hence Sjogren’s Syndrome in Patient 3, comprehensive workups for other aetiologies of myelitis were negative. Both Patient 2 and Patient 3 responded well with intravenous methylprednisolone (IVMP) during acute attacks/relapses, followed by long term maintenance therapy of prednisolone plus Mycophenolate Mofetil (MMF). Patient 3 received 1 cycle of add-on therapeutic plasma exchange once during a relapse with severe LETM. During the last follow-up, (i) Patient 1 demonstrated right eye blindness, (ii) Patient 2 demonstrated impaired colour vision of right eye, and (iii) Expanded Disability Status Scale was 1 in all 3 patients. Both Patient 2 and Patient 3 fulfilled the 2015 international consensus diagnostic criteria for NMOSD. Patient 1 passed away in 1989 without undergoing detailed para-clinical and neuroimaging investigations. Conclusion . Familial NMOSD may still be recognized despite an onset within the same generation with heterogenous phenotypic presentations, provided fulfilment of the international consensus diagnostic criteria.

NMOSD and MS prevalence in the Indigenous populations of Australia and New Zealand.

We studied the prevalence of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in Indigenous populations of Australia and New Zealand with the aim of assessing potential differences. Cases of possible NMOSD and MS were collected from Australia and New Zealand. Clinical details, MR imaging, and serologic results were used to apply 2015 IPND diagnostic criteria for NMOSD and 2010 McDonald criteria for MS. Frequencies of self-determined ethnic ancestry were calculated for confirmed NMOSD, suspected NMOSD, and MS. Prevalence rates for NMOSD and MS according to ancestry were compared. There were 75 cases with NMOSD, 89 with suspected NMSOD, and 101 with MS. NMOSD cases were more likely to have Asian, Indigenous, or Other ancestry compared to suspected NMOSD or MS. There were no differences in the clinical phenotype of NMOSD seen in Indigenous compared to European ancestry populations. Per 100,000, the prevalence estimate for NMOSD in people with Māori ancestry was 1.50 (95% CI 0.52-2.49) which was similar to those with Asian ancestry 1.57 (95% CI 1.15-1.98). NMOSD prevalence in Australian Aboriginal and Torres Strait Islander populations was 0.38 (95% CI 0.00-0.80) per 100,000. The prevalence of NMOSD in the Māori population is similar to South East Asian countries, reflecting their historical origins. The prevalence of MS in this group is intermediate between those with South East Asian and European ancestry living in New Zealand. Both NMOSD and particularly MS appear to be uncommon in the Indigenous populations of Australia.

Comparative study of AQP4-NMOSD, MOGAD and seronegative NMOSD: a single-center Belgian cohort

PurposeTo emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders). MethodsBased on Wingerchuk et al. (Neurology 85:177–189, 2015) criteria for NMOSD and on those more recently proposed by Jarius et al. (J Neuroinflammation 15:134, 2018) for MOGAD (MOG associated disorders), we retrospectively surveyed 10 AQP4-NMOSD, 8 MOGAD and 2 seronegative NMOSD, followed at the specialized neuroimmunology unit of the CHU Liège. ResultsFemale predominance was only observed in AQP4 group. Age at onset was 37.8 and 27.7 years old for AQP4-NMOSD and MOGAD respectively. In both groups, the first clinical event most often consisted of optic neuritis (ON), followed by isolated myelitis. Fifteen of our 20 patients encountered a relapsing course with 90% relapses in AQP4-NMOSD, 62.5% in MOGAD and 50% in seronegative group, and a mean period between first and second clinical event of 7.1 and 4.8 months for AQP4-NMOSD and MOGAD, respectively. In total we counted 54 ON, with more ON per patient in MOGAD. MOG-associated ON mainly affected the anterior part of the optic nerve with a papilledema in 79.2% of cases. Despite a fairly good visual outcome after MOG-associated ON, retinal nerve fibre layer (RNFL) thickness decreased, suggesting a fragility of the optic nerve toward further attacks.ConclusionAs observed in larger cohorts, our MOGAD and AQP4-NMOSD cases differ by clinical and prognostic features. A better understanding of these diseases should encourage prompt biological screening and hasten proper diagnosis and treatment.

Long-term safety of azathioprine for treatment of neuromyelitis optica spectrum disorders.

Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of São Paulo (São Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients' median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1-2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required.

Comparison of clinical characteristics and prognoses in patients with different AQP4-Ab and MOG-Ab serostatus with neuromyelitis optica spectrum disorders

BackgroundAt present, patients positive for aquaporin-4 antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab) are diagnosed as neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab-associated diseases, respectively. However, some patients who meet the diagnostic criteria for NMOSD and show demyelination of the central nervous system cannot be clearly classified. MethodsWe performed a prospective cohort study to evaluate the clinical characteristics and prognoses of double-seronegative patients with NMOSD. ResultsA total of 594 patients were included in the cohort, including 26 patients with MOG-Ab, 517 with AQP4-Ab, and 51 with double seronegativity. Compared to AQP4-Ab-positive patients, double-seronegative patients experienced less severe clinical attacks (51.0% vs. 78.1%; Pcorr < 0.01), either visual (23.5% vs. 42.6%; Pcorr = 0.024) or motor attacks (39.2% vs. 59.8%; Pcorr = 0.015), and had a better median Expand Disability Status Scale (EDSS) score at the last follow-up (2.0 vs. 3.0; Pcorr = 0.012) and a lower proportion of disability (11.8% vs. 30.9%; Pcorr = 0.015). Furthermore, lower risks of visual and motor disability were also observed by Kaplan–Meier analyses (P = 0.031 and 0.038, respectively). Both the MOG-Ab and double-seronegative groups had lower frequencies of severe clinical attacks, especially motor attacks, better EDSS scores at the last visit, and a lower proportion of disability than was found in the AQP4-Ab group (all P values and corrected P values <0.05). ConclusionsIn patients who met the diagnostic criteria for NMOSD, compared with AQP4-Ab-seropositive patients, double-seronegative and MOG-Ab-seropositive patients had less severe clinical attacks and better prognoses, including lower EDSS scores and a lower proportion of disability.

Relapsing neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disorder of the central nervous system. Relapsing NMOSD (RNMOSD) is being reported frequently, leading to severe and permanent relapse related disability.Aims and Objectives: To study the clinical profile and imaging features of the NMOSD cases at the index time and addressing the long-term clinical spectrum of relapsing type of NMOSD who presented to the tertiary care hospital. Materials and Methods: All patients who attended the King George Hospital, Visakhapatnam and fulfilled the diagnostic criteria of NMOSD were studied for the epidemiological details, type of clinical spectrum on relapses, imaging features and treatment prescribed, and were studied between April, 2011 and March, 2018.Results: Total diagnosed cases were 28, out of which relapsing type were seen in 11 patients and all tested positive for antibodies. Female to male ratio is 3:1, and in RNMOSD group all were females. Most common clinical presentation was myelitis followed by optic neuritis. Noted clinical spectrum in the RNMOSD was unusual presentations like one each patient of Area-Postrema syndrome, diencephalic syndrome, cerebral syndrome, acute brainstem syndrome, and frequent relapses within a month in two. Five cases had also associated systemic autoimmune disorders.Conclusion: RNMOSD is very rapidly evolving disease, affecting primarily young women with wide spectrum of neurological presentations and also other non-neurological systemic features. Early diagnosis and aggressive immune therapy in the early phase might be warranted in NMOSD for relapse prevention and improving the quality of life.

A case of area postrema variant of neuromyelitis optica spectrum disorder following SARS-CoV-2 infection

Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune astrocytopathic channelopathy, characterized by the presence of pathogenic antibodies to aquaporin-4 (AQP-4) water channels. Several viral infections including HIV, influenza virus, varicella zoster virus, and Epstein Barr virus, among others, have been alleged to trigger NMOSD in both immunocompetent and immunocompromised individuals. Neurological manifestations of coronavirus infectious disease of 2019 (COVID-19) have been ever evolving and the spectrum of neuraxial involvement is broadening. Albeit it may affect any area of the neural axis, the involvement of the spinal cord is rare compared to that of the brain and of the peripheral nervous system. Cases with acute longitudinally extensive transverse myelitis (LETM) have been recently reported in SARS-CoV-2 infection but did not fulfill the international consensus diagnostic criteria for NMOSD. AQP-4-antibody-seropositive NMOSD following SARS-CoV-2 infection had not yet been reported. We herein report a novel case of a previously healthy man who presented with a clinical picture of bouts of vomiting and hiccoughs (area postrema syndrome), which rapidly evolved to acute LETM, all following SARS-CoV-2 infection. He was finally diagnosed to be a case of seropositive NMOSD which presented as area postrema syndrome. The response to immunomodulatory drugs was excellent.

Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis: Diagnosis and Treatment

Optic neuritis (ON) is a frequent manifestation of aquaporin-4 (AQP4) antibody-mediated neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disorders, MOGAD). The past few years have seen major advances in the diagnosis and treatment of these two relatively new entities: international diagnostic criteria for NMOSD and MOG-EM have been proposed, improved antibody assays developed, and consensus recommendations on the indications and methodology of serological testing published. Very recently, the results of four phase III trials assessing new treatment options for NMOSD have been presented. With eculizumab, a monoclonal antibody inhibiting complement factor C5, for the first time a relapse-preventing long-term treatment for NMOSD - which has so far mostly been treated off-label with rituximab, azathioprine, and other immunosuppressants - has been approved. Data from recent retrospective studies evaluating treatment responses in MOG-ON suggest that rituximab and other immunosuppressants are effective also in this entity. By contrast, many drugs approved for the treatment of multiple sclerosis (MS) have been found to be either ineffective or to cause disease exacerbation (e.g., interferon-β). Recent studies have shown that not only NMOSD-ON but also MOG-ON usually follows a relapsing course. If left untreated, both disorders can result in severe visual deficiency or blindness, though MOG-ON seems to have a better prognosis overall. Acute attacks are treated with high-dose intravenous methylprednisolone and, in many cases, plasma exchange (PEX) or immunoadsorption (IA). Early use of PEX/IA may prevent persisting visual loss and improve the long-term outcome. Especially MOG-ON has been found to be frequently associated with flare-ups, if steroids are not tapered, and to underlie many cases of "chronic relapsing inflammatory optic neuropathy" (CRION). Both NMOSD-ON and MOG-ON are often associated with simultaneous or consecutive attacks of myelitis and brainstem encephalitis; in contrast to earlier assumptions, supratentorial MRI brain lesions are a common finding and do not preclude the diagnosis. In this article, we review the current knowledge on the clinical presentation, epidemiology, diagnosis, and treatment of these two rare yet important differential diagnoses of both MS-associated ON und idiopathic autoimmune ON.