Title Page
ABSTRACT
Contents
1. INTRODUCTION 11
1.1. Overview of autoimmune encephalitis 11
1.2. Recent advances in the treatment of autoimmune encephalitis 12
1.3. Seronegative autoimmune encephalitis 14
1.4. Purpose of research 15
2. MATERIALS AND METHODS 16
2.1. Study population 16
2.2. Testing for autoimmune encephalitis associated autoantibody 16
2.3. Testing for other etiologies of encephalitis 18
2.4. Analysis of clinical profiles 18
2.5. Analysis of brain imaging and cerebrospinal fluid parameters 19
2.6. Analysis of treatment profiles 20
2.7. Analysis of the predictors of 2-year outcomes 21
2.8. Analysis of the effect of immunotherapy 21
2.9. Effect of further immunotherapy on persistent disease 22
2.10. Serial brain MRI analysis 23
2.11. Statistical analysis 24
3. RESULTS 25
3.1. Patient characteristics 25
3.2. Factors associated with 2-year outcomes and the construction of RAPID scores 27
3.3. Analysis of the effect of immunotherapy 29
3.4. Effect of further immunotherapy on persistent disease 31
3.5. Serial brain MRI analysis 33
4. DISCUSSION 34
5. CONCLUSION 42
6. REFERENCES 43
7. FIGURES AND FIGURE LEGENDS 48
8. TABLES 60
9. 국문초록 80
Table 1. Comparison of clinical, laboratory, treatment, and outcome profiles among the disease subgroups. 60
Table 2. Comparison between groups with or without poor 2-year outcomes. 63
Table 3. Logistic regression analysis for the factors associated with the poor clinical course. 65
Table 4. Bootstrap validation for the logistic regression analysis of the factors associated with the poor clinical course. 66
Table 5. Linear mixed models for the longitudinal CASE score changes. 67
Table 6. Bootstrap validation for the linear mixed models for the longitudinal CASE score changes. 68
Table 7. Linear mixed models for the longitudinal CASE score changes in subgroups divided by RAPID scores. 69
Table 8. Bootstrap validation for the linear mixed models for the longitudinal CASE score changes in the subgroups divided by RAPID scores 70
Table 9. Repeated measure analysis of covariance for the comparison of the CASE scores before and after the use of... 71
Table 10. Profiles of the adverse events. 72
Table 11. Comparison of clinical, laboratory, treatment, and outcome profiles according to the groups with or without further... 73
Table 12. Logistic regression analysis for the factors associated with the improvement in mRS or CASE scores after 6-months until... 75
Table 13. Bootstrap validation for the logistic regression analyses for the factors associated with the improvement in mRS or CASE scores... 76
Table 14. Comparison of cerebrospinal fluid profiles at 6-month between the groups with or without additional mRS improvement... 77
Table 15. Comparison of clinical, laboratory, treatment, and outcome profiles according to the groups with or without further... 78
Fig. 1. A flow chart illustrating the process for defining the study population 48
Fig. 2. Clinical courses and outcomes of the study population. 49
Fig. 3. The association of the RAPID scores with 2-year outcomes. 50
Fig. 4. Association of the RAPID scores with 2-year outcomes in each disease subtype. 51
Fig. 5. The change in CASE scores before and after the initiation of rituximab or tocilizumab regimens. 52
Fig. 6. The effect of further immunotherapy on persistent disease at 6 months and at 12 months. 53
Fig. 7. The frequency of the development of brain atrophy in serial brain MRI follow-up and its association with the clinical outcomes. 54
Fig. 8. Brain MRI findings of representative patients. 55
Fig. 9. Illustrative diffusion restriction MRI finding in each disease subtype. 57