| PART ONE Clinical analysis and long-term outcomes of patients with neuropsychiatric systemic lupus erythematosusObjective:This study aims to analyze the prognosis,both mortality and morbidity,for patients with neuropsychiatric systemic lupus erythematosus(NPSLE)in a large single-center of Peking Union Medical College of Hospital(PUMCH).Methods:Patients with NPSLE in Peking union medical college hospital(PUUMCH)were collected retrospectively from June 2012 to June 2016,only neuropsychiatric events attributed to lupus was included.These patients were followed up by outpatient medical records and telephone follow-up.Data for baseline,follow-up and survival were collected;including demography,manifestations,activity(SLEDAI-2K),SLE International Collaborating Clinics Damage Index(SDI),and medications.SLE patients without any neuropsychiatric(non-NPSLE)syndromes from single-center CSTAR database were taken as control group.Clinical features of NPSLE patients compared with non-NPSLE patients were analysed by chi-square test or T test.Kaplan-Meier method was adopted for survival analysis and relapse analysis.Associated factors for increased SDI score were analyzed by Logistic Regression model.Result:In this study 188 patients were included,female to male is 12.4:1,the average age was 29.8±10.9 years(12 to 63 years).The median of SLE duration was 9 months(0-354months).In 94 patients(50.3%),NP syndrome occurred within the first year after SLE onset.69 patients(36.7%)had more than 1 NP syndromes.The average SLEDAI-2K scores was 20.4±9.2(0-44).41(21.8%)patients had SDI score more than one.Totally 265 NP events were manifested in these patients.Sixteen subtypes of NPSLE were identified,and the most frequent manifestations were seizure,acute confusion state,cerebral vascular disease,headache and psychosis.Compared with non-NPSLE patients,NPSLE patients had a significantly higher SLEDAI-2K score when the scores of NP syndrome were excluded.141 patients(75.0)accepted therapy of methylprednisolone pulse,and 134 patients(71.3%)accepted therapy of intrathecal injection.172 NPSLE patients were followed and 16 patients died during these years.The 1,2,3 and 4 year survival rates were 94.2%,92.7%,91.1%and 82.8%,respectively.The most common reason for death was infection.Kaplan-Meier analysis indicated that NPSLE significantly decrease the survival rate of SLE patients.Single factor analysis for survival rate of NPSLE patients indicated that SLEDAI-2K score>=15 or seizures significantly decrease the survival rate.The 1,2,year relapse rates were 3.1%,5.4%,respectively.Single factor analysis for relapse rate of NPSLE patients indicated that headache or abnormal cerebrospinal fluid cytology significantly increase the relapse rate.SDI score increased significantly and was associated with seizures and myelitis.67 NPSLE-seizures patients and 60 patients were followed.16 patients died,11 patients took antiepileptic drug at the time of the last follow-up,and 3 patients still had epileptic seizures.Logistic regression analysis indicated no relative factors with these results.29 NPSLE-CVD patients and 27 patients were followed.Patients with stroke were evaluated by modified Rankin Scale,and at the time of the last follow-up the function of stroke patients improved significantly.21 NPSLE-psychosis patients and 19 patients were followed.Patients with psychosis were evaluated by personal and social performance scale(PSP),and at the time of the last follow-up the function of these patients improved significantly.Conclusion:Most NPSLE events occurred in the presence of generalized disease activity.The most common subtype of NPSLE is seizure.NPSLE decrease the survival rate of SLE patients.Survival rates in our cohort are comparable to previous reported one.For NPSLE patients,SLEDAI-2K scores and seizures are prognostic factors and deserve more attention in the future.Most patients of seizures,CVD and psychosis have a favorable prognosis.PART TWO Magnetic resonance imaging result analysis and long-term outcomes of patients with neuropsychiatric systemic lupus erythematosusObjectives:To describe brain magnetic resonance imaging(MRI)abnormalities in neuropsychiatric systemic erythematosus lupus(NPSLE)and correlate them with clinical manifestation,laboratory data and prognosis.Methods:This retrospective cross-sectional study included patients presenting NPSLE undergoing brain MRI between 2012.6 and 2016.6.Clinical features,laboratory data and outcomes were recorded.MRI findings were defined as inflammatory-like,large-vessel disease(LVD),and small-vessel disease(SVD);SVD was classified as white-matter hyperintensities(WMH),recent small subcortical infarcts,lacunes,microbleeds,and brain atrophy.Results:We included 84 patients(mean 20.8 ± 10.2 years),97.6%women.The most frequent syndromes were seizures(41.7%),acute confusional state(20.2%),and headache(14.3%).Brain abnormalities were found in 67.9%.SVD was the most common(63.1%),followed by inflammatory-like lesions(8.3%)and LVD(3.6%).The most frequent SVD findings were WMH(47.6%),atrophy(22.6%),recent small subcortical infarcts(11.9%).SLE disease course more than one year correlated with WMH(p = 0.048),patients with more than one NP symptoms with atrophy(0.030),elevated protein in CSF with recent small subcortical infarcts(0.039).Headache correlated with normal MRI(0.036),cognitive disorder with atrophy.No relationship was found between MRI and autoimmune antibody.82 patients were followed and 7 patients died.Kaplan-Meier analysis indicated that inflammatory-like lesions significantly decreased the survival rate of NPSLE patients.Conclusions:Vascular disease is the hallmark of NPSLE.Certain syndromes and outcomes are prone to some brain damage.MRI could provide significant clinical information and insights into the pathological substrate.PART THREE Cerebrospinal fluid biomarkers in patients with neuropsychiatric systemic lupus erythematosusBackground and objective:Pathogenesis of NPSLE has not been well understood and different type of NPSLE may involve different pathophysiology.Earlier study had explored biomarkers in cerebrospinal fluid(CSF)through CSF proteomics applying Isobaric tags for relative and absolute quantization(iTRAQ)technology.Proteins associated with activation of gliocyte,neuroinflammation and structure or function of synapses is found modified in the CSF of NPSLE patients as compared to control groups.The objective of this study is to check the result.We chose 2 kinds of proteins associated with activation of gliocyte,chitinase 3-like protein 1(CHI3L1)and protease serine 2(PRSS2),and this study is to discuss the role of them in cerebrospinal fluid(CSF)in NPSLE and its clinical significance.Methods:18 NPSLE patients were included in this study and were divided into three groups according to NP subtype:the NPSLE-headache group,the NPSLE-psychosis group and the NPSLE-acute confusional state(ACS)group.Each group consisted of 6 patients.The clinical data and CSF of these patients was collected,and CSF after therapy was collected in some of these patients.The level of CHI3L1 and PRSS2 in CSF and serum was detected by ELISA.Result:Levels of CHI3L1 in CSF significantly elevated in NPSLE-ACS group compared to NPSLE-headache group(186.6±23.2 vs 104.1 ±67.3ng/ml,P=0.029)and NPSLE-psychosis group(186.6±23.2 vs 107.1±41.5ng/ml,p=0.004).There is no significant difference between NPSLE-psychosis group and NPSLE-headache group.No significant decline level of CHI3L1 in CSF was found after therapy.Levels of PRSS2 in CSF had no significant difference between each two group,yet between before and after therapy.Conclusion:Levels of CHI3L1 in CSF are significantly elevated in NPSLE-ACS group,indicating that the pathogenesis behind ACS is inflammation of central nervous system. |
PDF Full Text Request