We aimed to assess the treatment strategies utilized in patients with neuromyelitis optica spectrum disorder (NMOSD) experiencing relapses, including their frequency, types, and response after 6 months based on the Expanded Disability Status Scale (EDSS) score. Methods: We conducted a retrospective study involving NMOSD patients from the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177). Treatment response at 6 months was categorized as "good" if the EDSS score decreased by >1 point after a nadir EDSS score <= 3, or by >= 2 points after a nadir EDSS score > 3, "poor" if the EDSS score decrease was slighter, and as "absent" if the EDSS score remained unchanged or worsened. Results: We included 120 NMOSD patients (seropositive N = 75), who experienced 250 NMOSD-related relapses and received 248 treatments. At 6 months, complete recovery was achieved in 70/98 (71.4%) and 15/19 (79%) patients, respectively. Predictors of a "good" response in our regression model were a younger age at disease onset (OR:3.54, CI95% 2.45-5.01, p < 0.0001) and a short delay from onset of relapse to treatment initiation (OR:1.56, CI95% 1.22-2.13, p = 0.004). Conclusions: Approximately two-thirds of patients experienced complete recovery, and younger age and a short delay to start treatment were independent predictors of a "good" response.

Purpose: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. Methods: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naive (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. Results: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p symbolscript 0.03) and higher ARR pre-RTX (OR symbolscript 2.17, 95% CI 1.72-3.12, p symbolscript 0.002) but not with RTX regimen (OR symbolscript 1.10, 95% CI 0.89-1.21, p symbolscript 0.60).Conclusion: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

OBJECTIVES:We aimed to determinate the frequency of this association and compare the features of neuromyelitis optica spectrum disorder (NMOSD) with and without associated autoimmune diseases (AD) in a Latin American (LATAM) population in clinical practice.METHODS:We retrospectively reviewed the medical records of patients with NMOSD according to the 2015 diagnostic criteria. Patients from Argentina (n=77), Brazil (n=46), and Venezuela (n=17) were enrolled and classified into two groups as follows: with AD or without AD. Clinical, paraclinical (including aquaporin-4 antibodies (AQP4-ab) status), magnetic resonance imaging (MRI), and prognosis data were analyzed and compared. Kaplan-Meier (KM) and the Nelson-Aalen estimator analyses were performed to estimate both time and the cumulative hazard risk of disability reaching an EDSS≥4; and time for the first recurrence.RESULTS:Out of 140 patients, 33 (23.5%) patients had associated an AD at presentation. The most frequent associated AD was Hashimoto disease (n=10) followed by lupus (n=7) and Sjogren's syndrome (n=6). However, rituximab use (42.4% vs. 21.5%, p=0.02), female gender (82.2% vs. 100%, p=0.006), corticospinal lesions on MRI (0% vs. 12.5%, p=0.01) at onset, and positivity for antinuclear antibodies (21.2% vs. 48.4%, p=0.03) were significantly associated with NMOSD patients with AD in comparison to NMOSD patients without AD. No differences were found in other clinical and paraclinical aspects between groups. KM and Nelson-Aalen estimator analyses did not show differences between groups.CONCLUSION:NMOSD patients associated with AD were observed in 23.5%. In addition, NMOSD patients with and without associated AD were similar in most evaluated features.

Background: Optic neuritis (ON) can be an initial manifestation of neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin 4-antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD). Additionally, both diseases may have overlapping paraclinical and radiological features. These diseases may have different outcomes and prognoses. We aimed to compare clinical outcomes and prognostic features of patients with NMOSD and MOGAD presenting ON as first attack, from different ethnic groups in Latin America. Methods: We conducted a retrospective observational multicenter study in patients from Argentina (n = 61), Chile (n = 18), Ecuador (n = 27), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 49) with MOGAD or NMOSD related ON. Predictors of disability outcomes at last follow-up, namely visual disability (Visual Functional System Score >= 4), motor disability (permanent inability to walk further than 100 m unaided) and wheelchair dependence based on EDSS score were evaluated.Results: After a mean disease duration of 42.7 (+/- 40.2) months in NMOSD and 19.7 (+/- 23.6) in MOGAD, 55% and 22% (p>0.001) experienced permanent severe visual disability (visual acuity from 20/100 to 20/200), 22% and 6% (p = 0.01) permanent motor disability and 11% and 0% (p = 0.04) had become wheelchair dependent, respectively. Older age at disease onset was a predictor of severe visual disability (OR=1,03 CI95%1.01-1.05, p = 0.03); older age at disease onset (OR=1,04 CI95%1.01-1.07, p = 0.01), higher number of relapses (OR=1,32 CI95%1.02-1.71, p = 0.03) and rituximab treatment (OR=0,36 CI95%0.14-0.90, p = 0.02) were predictors of permanent motor disability, whereas ON associated with myelitis at disease onset was a predictor of wheelchair dependency (OR=4,16, CI95%1.23-14.08, p = 0,02) in NMOSD patients. No differences were found when evaluating distinct ethnic groups (Mixed vs. Caucasian vs. Afro-descendant)Conclusions: NMOSD was associated with poorer clinical outcomes than MOGAD. Ethnicity was not associated with prognostic factors. Distinct predictors of per-manent visual and motor disability and wheelchair dependency in NMOSD patients were found.

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75–2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients.

The objective was to evaluate time to reach an EDSS of 4, 6, and 7 in NMOSD and MOGAD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03,375,177). NMOSD patients diagnosed according to 2015 criteria and with MOGAD were identified. Patients with at least 3 years of follow-up and periodic clinical evaluations with EDSS outcomes were included. AQP4-antibody and MOG-antibody status was recorded, and patients were stratified as seropositive and seronegative for AQP4-antibody. EDSS of 4, 6, and 7 were defined as dependent variables. Log rank test was used to identify differences between groups. Registry data was provided for a total of 137 patients. Of these, seventy-five presented AQP4-ab-positive NMOSD, 45 AQP4-ab-negative NMOSD, and 11 MOGAD. AQP4-ab status was determined by cell-based assay (CBA) in 72

Background: Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders. Methods: A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients. Patients with complete relapse data (date, month and year) at onset and during follow-up were included. Attack counts were analyzed by month using a Poisson regression model with the median monthly attack count used as reference. Results: A total of 551 patients (431 MS and 120 NMOSD), experiencing 236 NMOSD-related attacks and 558 MS-related attacks were enrolled. The mean age at disease onset in NMOSD was 39.5 +/- 5.8 vs. 31.2 +/- 9.6 years in MS (p < 0.01). Mean follow-up time was 6.1 +/- 3.0 vs. 7.4 +/- 2.4 years (p < 0.01), respectively. Most of the included patients were female in both groups (79% vs. 60%, p < 0.01). We found a peak of number of attacks in June (NMOSD: 28 attacks (11.8%) vs MS: 33 attacks (5.9%), incidence rate ratio 1.82, 95%CI 1.15-2.12, p = 0.03), but no differences were found across the months in both disorders when evaluated separately. Strikingly, we observed a significant difference in the incidence rate ratio of attacks during the winter season when comparing NMOSD vs. MS (NMOSD: 75 attacks (31.7%) vs MS: 96 attacks (17.2%), incidence rate ratio 1.82, 95%CI 1.21-2.01, p = 0.02) after applying Poisson regression model. Similar results were observed when comparing the seropositive NMOSD (n = 75) subgroup vs. MS. Conclusions: Lack of seasonal variation in MS and NMOSD attacks was observed when evaluated separately. Future epidemiological studies about the effect of different environmental factors on MS and NMOSD attacks should be evaluated prospectively in Latin America population.

Background: We aimed to assess platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte ratios (NLR) for differentiating multiple sclerosis (MS) from aquaporin-4-antibody-positive neuromyelitis optica spectrum disorders (NMOSD) at disease onset.& nbsp;Methods: We retrospectively enrolled and reviewed the medical records of patients with MS (N = 50) and NMOSD (N = 33) followed in specialized MS/NMOSD centers from Argentina. Demographical and clinical (manifestation and disability) data and neuroradiological features (new/enlarging or contrast-enhancing lesions) were assessed at baseline, 1 and 2 years. Serum samples were obtained during the first relapse without a previous acute or chronic treatment, at 1 and 2 years. Mixed-effects model was used to identify independent associations between the log-transformed NLR or PLR and MS/NMOSD outcomes.& nbsp;Results: PLR is increased in NMOSD when compared to MS (229.4 +/- 86.74 vs. 186.6 +/- 70.17, P = 0.01), but no significant differences were found for NLR (3.51 +/- 1.29 vs. 3.30 +/- 1.17, P = 0.43). PLR was the only independent predictor of poor physical disability score (EDSS > 4) in NMOSD patients at 2 years (beta=0.28, p = 0.02) after applying multivariate mixed-effects regression analysis. Additionally, multivariate logistic regression analysis showed that the PLR was the only independent predictor of EDSS > 4 at 2 years (OR 28.8, p = 0.041) in the NMOSD group. The area under the receiver-operating characteristic curve was 0.841.& nbsp;Conclusion: PLR could be potentially useful as additional diagnostic tool in differentiating these two neuroinflammatory conditions at presentation. PLR can predict severity of neurological disability at 2 years in NMOSD patients.

Sequence variants in exon 2 of the Dynactin-1 gene (DCTN1) have been reported as causative of Perry (disease) Syndrome (PeD, MIM 168605), a rare neurodegenerative disorder characterized by parkinsonism, psychiatric symptoms, weight loss and hypoventilation [ [1] Farrer M.J. Hulihan M.M. Kachergus J.M. Dächsel J.C. Stoessl A.J. Grantier L.L. Calne S. Calne D.B. Lechevalier B. Chapon F. Tsuboi Y. Yamada T. Gutmann L. Elibol B. Bhatia K.P. Wider C. Vilarĩo-Güell C. Ross O.A. Brown L.A. Castanedes-Casey M. Dickson D.W. Wszolek Z.K. DCTN1 mutations in Perry syndrome. Nat. Genet. 2009; 41: 163-165https://doi.org/10.1038/ng.293 Crossref PubMed Scopus (245) Google Scholar ]. Here, we report the third family with the p.G67D variant in DCTN1.

ABSTRACT Background Multiple sclerosis (MS) is a chronic neurodegenerative and inflammatory disease. The adaptation to MS depends on the effectiveness of coping, which moderates the process of adaptation and psychological well-being. Objectives We aimed to analyze the coping strategies of an Argentinean population of patients with MS (PwMS) and their association with clinical variables and health-related quality of life (QoL). Methods A nationwide cross-sectional study. Screening instruments: Demographics and clinical data, coping strategies (Brief Coping Orientation to Problems Experienced, [COPE-28]), health-related QoL (MS Impact Scale, [MSIS-29]), Fatigue Severity Scale, and physical disability (self-administrated Expanded Disability Status Scale, [EDSS]). Results We included 249 PwMS. Most responders were female (74.7%) with a mean age at survey of 38.6 (±10.7) and had a MS duration of 7.3 years (range: 1–43 years) and a mean EDSS of 1.9 (±1.8). Younger age (r = −0.17), active MS (r = 0.25), higher fatigue (r = 0.22), MSIS-29 total (r = 0.34), MSIS-physical (r = 0.26), MSIS-psychological scores (r = 0.44), higher scores for perception of both severity of MS (r = 0.12) and wheelchair-dependency (r = 0.14) correlated significantly with the use of maladaptive coping strategies. However, active MS (β2.10, p = 0.01), MSIS-psychological score (β0.28, p < 0.0001), high education level (β − 1.15, p = 0.04), and EDSS (β − 0.84, p = 0.0001) were independent predictors of the utilization of maladaptive coping strategies after having applied multivariate analysis via linear regression. Conclusions Maladaptive coping strategies used by PwMS are associated with relevant clinical aspects of the disease and with worse health-related QoL scores.

We aimed to examine treatment interventions implemented in patients experiencing neuromyelitis optica spectrum disorders (NMOSD) attacks (frequency, types, and response). Methods Retrospective study. Data on patient demographic, clinical and radiological findings, and administered treatments were collected. Remission status (complete [CR], partial [PR], no remission [NR]), based on changes in the EDSS score was evaluated before treatment, during attack, and at 6 months. CR was analyzed with a generalized estimating equations (GEEs) model. Results A total of 131 patients (120 NMOSD and 11 myelin oligodendrocyte glycoprotein-antibody-associated diseases [MOGAD]), experiencing 262 NMOSD-related attacks and receiving 270 treatments were included. High-dose steroids (81.4%) was the most frequent treatment followed by plasmapheresis (15.5%). CR from attacks was observed in 47% (105/223) of all treated patients. During the first attack, we observed CR:71.2%, PR:16.3% and NR:12.5% after the first course of treatment. For second, third, fourth, and fifth attacks, CR was observed in 31.1%, 10.7%, 27.3%, and 33.3%, respectively. Remission rates were higher for optic neuritis vs. myelitis (p < 0.001). Predictor of CR in multivariate GEE analysis was age in both NMOSD (OR = 2.27, p = 0.002) and MOGAD (OR = 1.53, p = 0.03). Conclusions This study suggests individualization of treatment according to age and attack manifestation. The outcome of attacks was generally poor.

ABSTRACT Background: The real-world effectiveness of natalizumab in people with relapsing multiple sclerosis (PwRMS) in Argentina and Chile has not been reported. Objective: To evaluate the effectiveness of natalizumab treatment in PwRMS in Argentina and Chile, in clinical practice. Methods: We conducted a multicenter retrospective and observational study. We reviewed the medical records of PwRMS who had been treated with natalizumab for at least one year, without any interruption in MS treatment that lasted more than 12 weeks. We analyzed changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score and magnetic resonance imaging (MRI). Results: We enrolled 117 PwRMS treated with natalizumab. Natalizumab treatment was associated with a significant reduction in ARR from baseline after one year and two years of treatment (from 1.97 to 0.06 and 0.09 respectively; p<0.01 at each time point). From baseline, EDSS scores were reduced by 0.71 and 0.73 points at one and two years, respectively (p<0.01). No worsening of disability was observed in 82.9 and 67.5% of PwRMS at one and two years, respectively. The improvement in disability was 44.4% at one year and 39.3% at two years. During natalizumab treatment, the number of relapse-related hospitalizations was significantly reduced (p<0.01). MRI lesions (new/enlarging T2 or gadolinium-enhancing) were significantly reduced, compared with baseline. No evidence of disease activity was observed in 65% at two years of natalizumab treatment. Conclusions: Natalizumab significantly reduced disease activity in PwRMS in Argentina and Chile, in clinical practice. Natalizumab also decreased the number of hospitalizations compared with pre-natalizumab treatment.

BACKGROUND AND PURPOSE:Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM).METHODS:We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared.RESULTS:A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group.CONCLUSIONS:Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.