The influence of smoking on the pattern of disability and relapse risk in AQP4-positive Neuromyelitis Optica Spectrum Disorder, MOG-Ab Disease and Multiple Sclerosis.

BACKGROUND: the role of smoking on clinical outcomes of central nervous system (CNS) inflammatory disorders is unclear. To assess the effect of smoking on relapses and disability in neuromyelitis optica with aquaporin-4-antibodies (NMOSD-AQP4-Ab), Myelin Oligodendrocyte Glycoprotein-antibodies associated disease (MOGAD) and relapsing remitting Multiple Sclerosis (MS) patients. METHODS: in a UK cohort of 101 NMOSD-AQP4-Ab, 70 MOGAD and 159 MS, and a Korean cohort of 97 NMOSD-AQ4-Ab, time to first relapse, annualised relapse rate, onset relapse severity and recovery, time to Expanded Disability Status Score(EDSS)/secondary progressive MS (SPMS) were compared between never-smokers and ever-smokers. All clinical data were collected under the local ethics between January 2017 and January 2019. RESULTS: Smoking did not affect the risk of relapse in any of the diseases. The risk of reaching EDSS 6.0 in the UK NMOSD-AQP4-Ab cohort was higher in ever smokers but this did not achieve significance (HR 2.12, p=0.068). When combining the UK and Korea NMOSD-AQP4-Ab cohorts, poorer recovery from the onset attack was significantly more frequent in the ever-smokers versus the never smokers (55% vs 38%, p=0.04). In the MS cohort the risk of reaching EDSS 6 and SPMS was significantly higher in the ever-smokers (HR=2.67, p=0.01 and HR=3.18, p=0.001). In MOGAD similar patterns were seen without reaching significance. CONCLUSIONS: In NMOSD-AQP4-Ab smoking associates with worse disability not through an increased risk of relapses but through poor relapse recovery. As in MS, smoking cessation should be encouraged in NMOSD-AQP4-Ab.

Factors associated with fatigue in CNS inflammatory diseases with AQP4 and MOG antibodies.

OBJECTIVE: Fatigue is a common and disabling symptom amongst people with multiple sclerosis, however it has not been compared across the central nervous system (CNS) inflammatory diseases associated with aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). We explored the factors associated with fatigue within and across the two diseases, and compared fatigue levels between them. METHODS: We performed a cross-sectional study of 90 AQP4-Ab and 44 MOG-Ab patients. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS). Clinical, demographic, and psychometric (anxiety, depression, pain) data were used as independent variables. Multivariable linear regression was used to identify significant independent variables associated with fatigue within and across the two diseases. RESULTS: Within AQP4-Ab patients, age (P = 0.002), disease duration (P = 0.004), number of clinical attacks (P = 0.001), disability (P = 0.007), pain interference (P < 0.001), anxiety (P = 0.026), and depression (P < 0.001) were significant independent variables. Interestingly, disease duration had a negative association with fatigue (P = 0.004). Within MOG-Ab patients, pain interference score (P < 0.001) and anxiety (P = 0.001) were significant independent variables. Although fatigue was worse in AQP4-Ab patients compared to MOG-Ab patients (P = 0.008) in all patients as well as in those who ever had transverse myelitis (P = 0.023), this was driven by the differences in age, disability and pain interference rather than antibody subtype itself. INTERPRETATION: Multiple factors, but not the antibody specificity, appear to contribute to fatigue in antibody positive CNS inflammatory diseases. A multifaceted treatment approach is needed to better manage the physical, cognitive, and psychosocial aspects of fatigue in these patients.