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INTRODUCTION: 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. METHODS: 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). RESULTS: 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 10 days, 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. CONCLUSIONS: 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.
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Neuromielitis Óptica , Fenotipo , Humanos , Femenino , Masculino , Neuromielitis Óptica/terapia , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/fisiopatología , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Estudios de Seguimiento , Área Postrema , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. OBJECTIVES: To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. METHODS: We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. RESULTS: There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07-0.99; p = 0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01-0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01-0.67; p = 0.011) were negative risk factors for benign NMOSD. CONCLUSION: Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset.
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Mielitis , Neuromielitis Óptica , Niño , Humanos , Femenino , Masculino , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Acuaporina 4 , Tronco Encefálico , Inmunoglobulina G , Estudios Retrospectivos , AutoanticuerposRESUMEN
BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the CNS. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD (eculizumab, inebilizumab, and satralizumab), prompting the need to consider best practice therapeutic decision-making for this indication. Our objective was to develop validated statements for the management of AQP4-IgG-seropositive NMOSD, through an evidence-based Delphi consensus process, with a focus on recommendations for eculizumab, inebilizumab, and satralizumab. METHODS: We recruited an international panel of clinical experts in NMOSD and asked them to complete a questionnaire on NMOSD management. Panel members received a summary of evidence identified through a targeted literature review and provided free-text responses to the questionnaire based on both the data provided and their clinical experience. Responses were used to generate draft statements on NMOSD-related themes. Statements were voted on over a maximum of 3 rounds; participation in at least 1 of the first 2 rounds was mandatory. Panel members anonymously provided their level of agreement (6-point Likert scale) on each statement. Statements that failed to reach a predefined consensus threshold (≥67%) were revised based on feedback and then voted on in the next round. Final statements were those that met the consensus threshold (≥67%). RESULTS: The Delphi panel comprised 24 experts, who completed the Delphi process in November 2021 after 2 voting rounds. In round 1, 23/25 statements reached consensus and were accepted as final. The 2 statements that failed to reach consensus were revised. In round 2, both revised statements reached consensus. Twenty-five statements were agreed in total: 11 on initiation of or switching between eculizumab, inebilizumab, and satralizumab; 3 on monotherapy/combination therapy; 7 on safety and patient population considerations; 3 on biomarkers/patient-reported outcomes; and 1 on research gaps. DISCUSSION: An established consensus method was used to develop statements relevant to the management of AQP4-IgG-seropositive NMOSD. These international statements will be valuable for informing individualized therapeutic decision-making and could form the basis for standardized practice guidelines.
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Neuromielitis Óptica , Humanos , Acuaporina 4 , Consenso , Técnica Delphi , Inmunoglobulina G , Neuromielitis Óptica/tratamiento farmacológicoRESUMEN
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 permanent visual and motor disability and wheelchair dependency in NMOSD patients were found.
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Personas con Discapacidad , Trastornos Motores , Neuromielitis Óptica , Neuritis Óptica , Humanos , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico por imagen , Acuaporina 4 , Estudios Retrospectivos , Pronóstico , Etnicidad , América Latina/epidemiología , Neuritis Óptica/diagnóstico por imagen , AutoanticuerposRESUMEN
Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON. Trial registration: ClinicalTrials.gov, identifier: NCT05605951.
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INTRODUCTION: We sought insights into the classification of and factors associated with relapse severity and disease stability in neuromyelitis optica spectrum disorder (NMOSD) clinical practice worldwide. METHODS: Neurologists recruited from six countries (the USA, Germany, Italy, Brazil, South Korea, and China) participated in a 30-60 minute online survey and submitted two to four clinical records for aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive adults with NMOSD, which included patient demographics, diagnosis, maintenance treatment history, relapse occurrence, and severity. Separately, patients with NMOSD receiving maintenance therapy were interviewed over the telephone about their treatment journey, as well as perceptions of relapse severity and disease stability, and their potential influence on treatment decisions. RESULTS: Clinical records for 1185 patients with AQP4-IgG-seropositive NMOSD were provided by 389 neurologists (July-August 2020); 33 patients were interviewed (October-November 2020). There was no clear consensus on how relapse severity was defined in clinical practice, with geographical variations in relapse classification also found. Neurologists tended to rely on clinical assessments when determining severity, viewing each relapse in isolation, whereas patients had a more subjective view based on the changes in their daily lives and comparisons with prior relapses. Similarly, there was a disconnect in the definition of disease stability: the complete absence of relapses was more important for patients than for neurologists. CONCLUSION: A clear consensus on how to assess relapse severity and disease stability is needed to ensure that patients receive appropriate and timely treatment. In the future, clinical measures should be combined with patient-focused assessments.
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INTRODUCTION: We sought insights into neuromyelitis optica spectrum disorder (NMOSD) treatment practices worldwide. METHODS: Neurologists from the USA, Germany, Italy, Brazil, South Korea, and China completed an online survey, contributing clinical records for aquaporin-4 (AQP4) immunoglobulin G (IgG)-seropositive adults with NMOSD, which included patient demographics, diagnosis, maintenance treatment history, relapse occurrence, and severity. Interviewed patients receiving NMOSD maintenance therapy provided information about their diagnosis, treatment, perceptions about relapse severity or disease stability, and treatment switches. RESULTS: A total of 389 neurologists submitted clinical records for 1185 patients with AQP4-IgG-seropositive NMOSD; 33 patients with NMOSD were interviewed. Approximately 25% (228/910) of patients from the clinical record review (CRR) were initially misdiagnosed; 24% (8/33) of patients interviewed reported formal misdiagnosis. Misdiagnosis was associated with treatment delay and more relapses compared with correct diagnosis (mean 3.3 vs 2.8). Maintenance therapy was not initiated within 2 months for 47% (221/472) of patients from the CRR and 24% (8/33) of interviewed patients. Oral corticosteroids/immunosuppressive therapies were typically the first maintenance treatment initiated, except for the USA, where monoclonal antibodies were equally likely to be prescribed. Relapse severity influenced the decision to initiate/change therapy and use monoclonal antibodies. Of interviewed patients, 76% (25/33) did not recall having a choice of treatment and many did not know the rationale for treatment choice. CONCLUSION: Misdiagnosis of NMOSD appears to be common and is associated with a delay in initiation of maintenance therapy, with decisions influenced by relapse severity. Further real-world studies assessing relapse severity in treatment initiation/switch are required to revise NMOSD treatment recommendations.
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BACKGROUND: The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC). METHODS: Twenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics. RESULTS: The discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%). CONCLUSIONS: Results support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.
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Acuaporinas , Neuromielitis Óptica , Neuritis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Estudios Retrospectivos , Benchmarking , Neuritis Óptica/diagnóstico , Tomografía de Coherencia Óptica/métodos , Autoanticuerpos , Acuaporina 4RESUMEN
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 naïve (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 = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 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.
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Neuromielitis Óptica , Humanos , Rituximab/efectos adversos , Estudios Retrospectivos , América Latina , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/inducido químicamente , Recurrencia , Acuaporina 4 , Autoanticuerpos/uso terapéuticoRESUMEN
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.
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Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , América Latina , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica/diagnóstico por imagenRESUMEN
BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.
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Acuaporina 4/sangre , Neuromielitis Óptica/fisiopatología , Retina/fisiopatología , Adulto , Astrocitos/patología , Autoanticuerpos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND AND OBJECTIVES: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts. METHODS: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA). RESULTS: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 µm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 µm, p < 0.001). GCIP layer loss (-22.7 µm) after the first ON was higher than after the next (-3.5 µm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC. DISCUSSION: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.
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Acuaporina 4/inmunología , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/patología , Neuritis Óptica/inmunología , Neuritis Óptica/patología , Neuronas Retinianas/patología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/diagnóstico por imagen , Neuritis Óptica/diagnóstico por imagen , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
BACKGROUND: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible. OBJECTIVE: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil. METHODS: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS. RESULTS: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations. CONCLUSIONS: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Brasil/epidemiología , Ciudades/epidemiología , Femenino , Humanos , Esclerosis Múltiple/epidemiología , PrevalenciaRESUMEN
BACKGROUND: Recent changes to the diagnostic criteria for multiple sclerosis (MS) and new medications have had a major impact on the way in which specialists manage the disease. OBJECTIVE: To investigate factors considered by Brazilian neurologists in managing MS, and to identify how these contribute to diagnosis and treatment. METHODS: Potential participants were selected by a steering committee (MS experts who developed this survey). Only MS specialists were included in the study (neurologists who had completed a neuroimmunology fellowship or who were treating more than 30 MS patients). Links to the online questionnaire were distributed between March 2019 and January 2020. This questionnaire was composed of sections with hypothetical MS scenarios. RESULTS: Neurologists from 13 Brazilian states responded to the survey (n = 94). In the clinically isolated syndrome (CIS) scenario, the respondents agreed to treat patients with a high risk of MS diagnosis, whereas in the radiologically isolated syndrome (RIS) half of the respondents opted not to treat, even among high-risk patients. In cases of low-activity relapsing-remitting MS (RRMS), the choice of treatment was distributed among interferon beta, glatiramer acetate and teriflunomide, which were changed to fingolimod and natalizumab, as RRMS severity increased. The topics in which disagreement was found included practices regarding use of disease-modifying therapy (DMT) for pregnant patients and the washout period required for some DMTs. CONCLUSIONS: This study enabled identification of areas of agreement and disagreement about MS treatment among Brazilian neurologists, which can be used to update future protocols and improve patient management.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Femenino , Acetato de Glatiramer , Humanos , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/uso terapéutico , Neurólogos , EmbarazoRESUMEN
ABSTRACT Background: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible. Objective: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil. Methods: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS. Results: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations. Conclusions: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.
RESUMO Introdução: Para melhor comparar a prevalência de esclerose múltipla (EM) nas diferentes regiões do Brasil, o Comitê Brasileiro para Tratamento e Pesquisa em Esclerose Múltipla implementou uma abordagem padronizada para avaliar a prevalência da doença em 5 cidades-chave, consideradas representativas de suas regiões em termos de características sociogeográficas e nas quais seria viável revisar cada caso pessoalmente. Objetivos: Descrever a prevalência pontual de EM em Passo Fundo, uma das cidades-chave, localizada no Sul do Brasil. Métodos: Buscamos identificar todos os pacientes com EM que viviam em Passo Fundo no dia 1( de julho de 2015. A fonte primária para identificação de casos foi os registros de consultórios de neurologistas e neurocirurgiões da cidade. Múltiplas fontes secundárias foram usadas para maximizar a identificação de casos. Todos os pacientes tiveram o diagnóstico revisado pessoalmente por um painel de neurologistas com experiência em EM. Resultados: Identificamos 52 pacientes com EM que viviam em Passo Fundo em 1( de julho de 2015. Assim, a prevalência pontual bruta de EM foi 26,4/100.000 habitantes (intervalo de confiança de 95%, 19,7 a 34,6/100.000). Entre os casos de EM, 42 (80,8%) eram mulheres, (razão de sexos: 4,2:1). Quarenta e seis casos (88,5%) foram categorizados como EM remitente-recorrente, e os 6 casos restantes como EM secundariamente progressiva (11,5%). As demais características epidemiológicas e clínicas foram comparáveis a populações de EM internacionais. Conclusões: A prevalência de EM em Passo Fundo é uma das maiores já relatadas no Brasil. Estudos em outras cidades-chave brasileiras, usando a mesma metodologia, estão em andamento.
Asunto(s)
Humanos , Femenino , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple/epidemiología , Brasil/epidemiología , Prevalencia , Ciudades/epidemiologíaRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.
Asunto(s)
Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , América Latina/epidemiología , Glicoproteína Mielina-Oligodendrócito , Recurrencia Local de Neoplasia , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/terapiaRESUMEN
BACKGROUND: The Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) has launched an initiative to determine the prevalence of multiple sclerosis (MS) in Brazil, based on key cities deemed representative of their regions in terms of demographic and environmental features. OBJECTIVE: To investigate the prevalence rate of MS in Joinville. METHODS: We reviewed the medical records of all patients who lived in Joinville and met the 2010 McDonald's diagnostic criteria revised for MS on the prevalence day (March 11, 2016). Potential MS patients included individuals treated by all practicing neurologists in the city and the ones found in patients' association and the database of the Municipal Department of Health. Advertisements about the survey were also broadcast on radio and television. Patients who were not living in Joinville on the prevalence day were excluded. All potential MS patients were invited to an in-person diagnostic review, carried out by a panel of experienced neurologists with special expertise in MS on March 11, 2016. RESULTS: The MS prevalence rate was 13.5 per 100,000 inhabitants (95% confidence interval [95%CI] 12.9-14.0/100,000). A total of 51 (66.2%) participants were females, and 26 (33.7%) were males (female to male ratio=1.9:1). Out of the 77 patients, 73 (94.8%) were Caucasians, and four (5.1%) were mixed-race. CONCLUSIONS: Despite its latitude location and European colonization, the prevalence rate was below expectation. The intense internal migration from regions with lower MS prevalence rates to Joinville may have played a role in attenuating the increased risk of MS associated with latitude gradient and European ancestry. Prevalence studies in other cities from Southern Brazil with no significant internal migration and taking part in this broad project may clarify this issue.
Asunto(s)
Esclerosis Múltiple , Brasil/epidemiología , Ciudades/epidemiología , Femenino , Humanos , Masculino , Esclerosis Múltiple/epidemiología , Prevalencia , Población BlancaRESUMEN
BACKGROUND: Basic steps in the management of patients with Multiple Sclerosis (MS), such as good patient understanding of the disease and active participation in its management are extremely important, as they directly influence treatment adherence and success. Therefore, this study aimed to evaluate the perception of MS patients and neurologists pertaining to the most common disease symptoms, disabilities that impact on quality of life, and patient concerns and difficulties during medical visits, as information that can be used to improve the doctor-patient relationship. METHODS: A cross-sectional study involving two groups: the first composed of neurologists and the second of patients. Participants of the first group were selected by a Steering Committee (15 predetermined neurologists representing each region of Brazil and specialized in MS and neuroimmunological disorders, who also assumed the role of creating the survey and questionnaire). Participants of the second group were selected following dissemination of a questionnaire on the AME's social networks (Amigos Múltiplos pela Esclerose, a non-governmental organization to support patients with MS). Questions about sociodemographic data, disease impact on quality of life, symptoms perception, and concerns and issues regarding disease care were put to both groups. RESULTS: A total of 317 patients and 182 neurologists answered the questionnaires. Significant divergences were found between the perceptions of patients and neurologists in relation to orientation and information given during medical appointments, and also regarding patient participation in treatment and therapy choice. Considering the topic assessing impact on quality of life, more than 70% of neurologists perceived that autonomy to work and travel, and future planning were aspects that most affected patient lives, however, almost 50% of patients reported that disease monitoring did not affect their life in any way. Analysis of data regarding MS symptoms revealed neurologists to consider physical symptoms, such as ambulation issues, imbalance, falls and urinary incontinence, to be those most interfering with patient quality of life, whereas patients considered non-physical symptoms, such as fatigue, pain, cognitive and memory problems to be more significant. Patients with primary progressive MS complained more about ambulation issues, imbalance and falls (p<0.05), when compared to patients with other disease phenotypes. CONCLUSION: Significant differences in disease perception were found in this study. While neurologists tended to overestimate the consequences and symptoms of the disease, for most patients, the disease impact on activities did not appear to be as significant, with more complaints regarding non-physical symptoms. Although neurologists described involving patients in treatment decisions and providing them with appropriate orientation during medical appointments, the opposite was reported by patients. These results may help to improve treatment adherence and disease outcomes by redefining the doctor-patient relationship.