| Objective To compare the clinical characteristics of early-onset NMOSD(EO-NMOSD),late-onset NMOSD(LO-NMOSD)and very late-onset NMOSD(VLO-NMOSD)and analyze the characteristics of patients with very late-onset NMOSD.To compare the clinical characteristics of female patients with NMOSD at different stages of fertility and explore the features of female NMOSD.To investigate cerebrospinal fluid(CSF)biomarkers of NMOSD and their association with clinical characteristics,including protein,adenosine deaminase(ADA),lactic acid,β2-microglobulin(β2-MG)etc.To measure CSF and serum YKL-40 levels in patients with NMOSD and investigate the association with disease severity.MethodsPart Ⅰ:(1)To retrospectively analyze the medical records of 72 patients with acute NMOSD hospitalized in the Tianjin Medical University General Hospital from September 2018 to January 2020,and collect the general information,clinical manifestations,MRI and laboratory data.Patients were divided into three groups according to the age of first onset: EO-NMOSD(first onset age <50 years),LO-NMOSD(50 years old ≤ first onset age <70 years old)and VLO-NMOSD(first onset age ≥ 70 years old).To compare and summarize the differences in the clinical characteristics of the three groups and analyze the clinical characteristics and heterogeneity of VLO-NMOSD.Female patients were divided into three groups according to fertility.To compare the clinical characteristics of female patients of the three groups and explore the features of female NMOSD.Part Ⅱ: A total of 38 patients with acute NMOSD admitted to Tianjin Medical University General Hospital from March 2018 to June 2020 were selected as experimental group,while 21 cases of other non-inflammatory neurological diseases(ONNDs)were selected as disease control group.The differences of biochemical index of CSF protein,lactate dehydrogenase(LDH),ADA,hypersensitivity C reaction protein(hs-CRP),glucose,chlorine,lactic acid,β2-MG were compared that measured by automatic biochemical instruments.The correlation between CSF protein,lactate,β2-MG and clinical characteristics were analyzed in patients with NMOSD.Part Ⅲ: A total of 29 patients with acute NMOSD admitted to Tianjin Medical University General Hospital from March 2018 to September 2019 were selected as experimental groups,while 21 cases of ONNDs as disease control group and 21 cases as healthy control were selected.The serum and CSF YKL-40 levels were measured and the associations between CSF YKL-40 levels and clinical characteristics of NMOSD were analyzed.ResultsPart Ⅰ:(1)A total of 72 patients with NMOSD were included.The age range of the first episode was 15-78 years old,and the average age was 44.6 ± 15.6 years old.There were 64 females and 8 males,the female-to-male ratio was 8:1.54 cases were positive for AQP4-Ab,and the positive rate was 75%.There were 15(20.8%)cases of other autoimmune diseases.(2)There were significant differences in the course of disease between different groups of NMOSD(p = 0.007).The course of disease in VLO-NMOSD was significantly shorter than EO-NMOSD(p = 0.003),while there was no significant difference between the EO-NMOSD and LO-NMOSD(p = 0.051).There was no significant difference between EO-NMOSD and LO-NMOSD(p = 0.081).(3)There were significant differences in the nadir EDSS score between different groups of NMOSD(p = 0.004).The nadir EDSS score of VLO-NMOSD and LO-NMOSD groups were significantly higher than EO-NMOSD(p = 0.022,p =0.035).There were no significant differences between VLO-NMOSD and LO-NMOSD(p = 0.569).(4)There were significant differences in the the positive rate of serum AQP4-Ab between different groups of NMOSD.The VLO-NMOSD had the highest percentage(100%),while the EO-NMOSD group had the lowest percentage(63.4%).(5)There were significant differences in the course of female NMOSD at different fertility(p = 0.030).The course of NMOSD in postnatal group was longer than that in postmenopausal group(p < 0.001),while there was no significant difference between other groups(p > 0.05).(6)There were significant differences in nadir EDSS score of female NMOSD at different stages of fertility among the groups when the disease was most severe(P =0.001).The nadir EDSS score of female NMOSD in menopause were significantly higher than other two groups(p = 0.003,p = 0.002).Part Ⅱ:(1)The CSF levels of protein were significantly higher in patients with NMOSD than ONNDs(0.5 ± 0.3 g/L vs 0.3± 0.1 g/L,p = 0.002).The CSF levels of ADA were significantly higher in patients with NMOSD than ONNDs(0.6 ± 0.5 U/L vs 0.3 ± 0.1 U/L,p = 0.002).The CSF levels of lactate were significantly higher in patients with NMOSD than ONNDs(1.9 ± 0.5 mmol/L vs 1.6 ± 0.4 mmol/L,p =0.004).The CSF levels of β2-MG were significantly higher in patients with NMOSD than ONNDs(1.9 ± 0.9 mg/L vs 1.2± 0.6 mg/L,p< 0.001).(2)CSF levels of ADA positively correlated with protein levels in patients with NMOSD(r = 0.496,p = 0.002).CSF levels of lactate positively correlated with protein and ADA(r = 0.591,p < 0.001;r = 0.369,p = 0.023).CSF levels of β2-MG positively correlated with protein and lactate(r = 0.438,p = 0.006;r = 0.416,p =0.009).(3)The level of CSF protein positively correlated with the EDSS score in patients with NMOSD(r = 0.417,p = 0.009).The level of CSF lactate positively correlated with the EDSS score and the length of the spinal cord lesions in patients with NMOSD(r = 0.341,p = 0.036;r = 0.357,p = 0.028).Part Ⅲ:(1)The patients with NMOSD had significantly higher CSF YKL-40 levels than those in patients with ONNDs(293.6 ± 33.9 ng/ml vs.117.1 ± 17.1 ng/ml,p <0.001).There were no significant differences in the serum YKL-40 levels between patients with NMOSD and the healthy controls(38.6 ± 6.1 ng/ml vs.35.1 ± 5.8 ng/ml,p = 0.723).(2)Subgroup analyses indicated that patients with MRI-enhanced lesions had significantly higher CSF YKL-40 levels than those without MRI-enhanced lesions(354.6 ± 52.3 ng/ml vs.218.5 ± 30.4 ng/ml,p = 0.034).However,there were no differences in the CSF YKL-40 levels between other subgroups.(3)The level of CSF YKL-40 positively correlated with the EDSS score of the patients with NMOSD(r = 0.384,p = 0.040).Conclusions(1)Patients with VLO-NMOSD tend to be more severe with short disease duration.(2)Female patients with NMOSD tend to be more severe after menopause.(3)The CSF protein levels of NMOSD patients were increased and correlated with the severity of the disease.(4)The CSF level of lactic acid of NMOSD patients were increased and correlated with the severity of the disease and segments of spinal cord lesions.(5)Increased levels of CSF β2-microglobulin,a nonspecific inflammatory indicator of NMOSD,were associated with levels of CSF protein and lactic acid.(6)YKL-40 may play an important role in the pathogenesis of NMOSD.The increased CSF levels of YKL-40 positively correlated with the severity of disease in patients.YKL-40 could be a NMOSD severity biomarker and a potential target for NMOSD treatment. |
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