BACKGROUND: 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.
CONCLUSIONS: 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.

Background: Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. Verified biomarkers are not available for AD and its relapse, although the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) may play important roles in the mechanism of addiction. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence. Methods: Sixty-eight hospitalized early-abstinence AD male patients and 68 age- and education-matched healthy controls (HCs) underwent resting-functional magnetic resonance imaging (r-fMRI). Using the NAc and mPFC as seeds, we calculated changes in FC between the seeds and other brain regions. Over a follow-up period of 6 months, patients were measured with the Alcohol Use Disorder Identification Test (AUDIT) scale to identify relapse outcomes (AUDIT ≥ 8). Results: Thirty-five (52.24%) of the AD patients relapsed during the follow-up period. AD displayed lower FC of the left fusiform, bilateral temporal superior and right postcentral regions with the NAc and lower FC of the right temporal inferior, bilateral temporal superior, and left cingulate anterior regions with the mPFC compared to controls. Among these FC changes, lower FC between the NAc and left fusiform, lower FC between the mPFC and left cingulate anterior cortex, and smoking status were independently associated with AD. Subjects in relapse exhibited lower FC of the right cingulate anterior cortex with NAc and of the left calcarine sulcus with mPFC compared to non-relapsed subjects; both of these reductions in FC independently predicted relapse. Additionally, FC between the mPFC and right frontal superior gyrus, as well as years of education, independently predicted relapse severity. Conclusion: This study found that values of FC between selected seeds (i.e., the NAc and the mPFC) and some other reward- and/or impulse-control-related brain regions were associated with AD and relapse; these FC values could be potential biomarkers of AD or for prediction of relapse. These findings may help to guide further research on the neurobiology of AD and other addictive disorders.