This study is the first to evaluate clinical and demographic features in the Brazilian northeast region. Although our study is not population-based, we believe that we were able to investigate a significant proportion of patients with NMOSD in the state of Bahia since our study center is the only reference center in the state.
Despite methodological differences and disparities in the definition of NMOSD over the years, we have a similar average age at onset compared to most studies, as well as the higher prevalence in women, with female: male proportions > 3:1[6–8, 10, 22–24]. Our sample has a higher percentage of afro-descendant patients (73.6%) compared to other international studies and even compared with other studies in Brazil. [6–8, 10, 22–24]. This could be due to the population profile of the study location, the city of Salvador, state of Bahia, which concentrates the highest proportion of black people outside Africa [13]. The higher prevalence of NMOSD among Afro-descendant populations explains the sample size of this study, which is comparable to prior multicenter studies that evaluated epidemiological aspects of entire countries [10, 11].
Despite this peculiarity, we did not find a significant association between the race of patients and worst clinical outcomes. This association shows a great divergence in the literature. A previous study demonstrated that race is not an independent factor of worse motor or visual prognosis [17]. Another author demonstrates that there is an association between the white race and worse visual outcomes and higher EDSS scores [14]. In addition, some papers found worse prognosis in Afro-Caribbean patients [18, 25]. Due to the wide miscegenation of the population it’s difficult to define race in this Brazil, thus the racial stratification analyzed in this study was based on the patients’ phenotype.
The AQP4-IgG seropositivity was observed in 73.3% of patients, in accordance with prior studies [6, 7, 22, 24]. Other authors found a lower frequency of AQP4-IgG seropositivity [8, 11]. This divergence can be attributed to the methodology used and the timing of the antibody test. Although in some studies the seropositivity of AQP4-IgG antibody has been associated with more severe impairment [15, 26, 27]. Others, similar to our results, showed no association [11, 22].
According to many studies transverse myelitis was the most prevalent syndrome of initial attack (32.9%) [7, 10, 28]. The classic presentation of simultaneous ON and TM was observed in 21.2% of the patients, a percentage that is in agreement with other samples. [7, 8, 22]. However, it was smaller than the percentage observed in other cohorts [6, 10]. Another important feature of our sample is that 5.9% of the patients had ON, TM and APS simultaneously in the initial presentation. This data can be explained by another study that demonstrated that combined initial clinical syndromes are more frequent in Afro-American and Afro-European populations [17].
With regards to comorbid autoimmune diseases, the frequency in our sample is similar (10.2%) to what was shown in some previous studies [6, 8]. When compared to others studies, however, where up to a third of patients presented this type of comorbidity, our percentage was lower [10, 11, 22]. In our study, we observed that Hashimoto's thyroiditis was the most frequent autoimmune disease, followed by systemic lupus erythematosus, comorbidities that were previously associated with NMOSD [29]. Furthermore, the percentage of comorbid autoimmune diseases tended to be higher in patients with disease progression, but this association was not statistically significant in the multivariate analysis. A prior study described an association between concomitance of other autoimmune diseases and greater disability [30].
The annualized relapse rate as well as the frequency of relapsing remitting phenotype among patients were similar to the described in the literature. However, we found a progression index of 2.3 (±4.1), an index higher than the one reported in a previous southeastern Brazilian study [8]. Regarding the treatment options, the most frequent type of maintenance therapy used was the combination of azathioprine and glucocorticoid, which is accordant to other studies [8, 11, 22].
Concerning the prognostic factors, a higher age at the initial symptomatic presentation was associated with worst clinical outcome, as reported previously [31, 32]. Our findings also suggest that patients who had area postrema lesions could have worst disease outcomes. Previous studies indicate the medulla oblongata is a highly frequent CNS structure involved in NMOSD (prevalence varying between 12.8% and 91.3%), with lesions usually occurring in its dorsal part [33–36]. One study demonstrated that patients with medullary lesions were more likely to have a higher number of brain injuries, as well as disease with elevated clinical activity and rapid progression, hence reporting higher EDSS and annualized relapse rate scores [37]. To explain this more severe behavior among patients with area postrema injuries, we speculate that: 1) the signs and symptoms resulting from lesions in this topography can more severely increase the EDSS; 2) these patients are more often affected by a greater number of brain and extensive spinal cord injuries, which could have an impact on the severity of the disease.
Although it is not clear if the initial clinical syndrome type has an influence on prognosis, our study found that optic neuritis as first presentation was associated with slow disease progression. A recent retrospective study demonstrated that optic neuritis as initial presentation of NMOSD correlated to worst visual outcome, with no differences regarding EDSS [14]. One study showed that patients with optic neuritis as an initial symptom of multiple sclerosis took more years to achieve EDSS 4.0, 6.0 and 7.0 when compared to patients without neuritis [38]. Similarly, another study reported that patients who had optic neuritis as initial attack (clinically isolated syndrome) had a lower rate of conversion to multiple sclerosis, when compared to other types of first disease presentation [39]. However, this type of optic neuritis differs from atypical optic neuritis, as generally seen in NMOSD and further prospective studies are needed to investigate the real influence of the initial syndrome on the prognosis of patients.
One of the most unexpected aspects of the present study was the finding of dyslipidemia as a factor associated to a better prognosis, a feature that was not analyzed in most of the previous epidemiological cohorts. This result is contrary to a previous observation that hypertriglyceridemia may be related to a worse recovery from the first demyelinating NMOSD attack [40]. One of the theories suggested to explain this finding is that dyslipidemic patients may have used hypolipidemic drugs as a long term treatment, such as statins, that have pleotropic anti-inflammatory effects and, therefore, a possible beneficial effect on disease control [41]. A second possible explanation is that the inflammatory activity is associated with reduction in LDL levels, as observed in other inflammatory diseases, such as rheumatoid arthritis, and in acute stress conditions, such as sepsis [42]. Thus, this could disguise the diagnosis of dyslipidemia in patients with greater inflammatory activity.