Factors Affecting the Response to First-Line Treatments in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Abstract

Background and Purpose Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study aimed to explore the possible factors affecting the response to first-line treatments in patients with anti-NMDAR encephalitis. Methods We enrolled 29 patients who were diagnosed as anti-NMDAR encephalitis between January 1, 2015, and June 30, 2018. They were divided into the remission and nonremission groups according to their response to first-line treatments. The demographics, clinical manifestations, main ancillary examinations, follow-up treatments, and prognosis of patients were recorded. The symptoms reported on in this study occurred before treatments or during the course of first-line treatments. Results There were 18 patients (62.07%) in the remission group and 11 patients (37.93%) in the nonremission group. Compared to the remission group, a higher proportion of the patients in the nonremission group exhibited involuntary movements, decreased consciousness, central hypoventilation, lung infection, and hypoalbuminemia. The nonremission group had a high incidence of increased intracranial pressure and significant elevations of the neutrophil-to-lymphocyte ratio in peripheral blood (NLR), aspartate aminotransferase, and fibrinogen. Six patients (54.55%) in the nonremission group received second-line immunotherapy. Only one patient (3.45%) died, which was due to multiple-organ failure. Conclusions Anti-NMDAR-encephalitis patients with more symptoms—especially involuntary movements, disturbance of consciousness, central hypoventilation, and accompanying hypoalbuminemia and pulmonary infection—may respond poorly to first-line treatments. Positive second-line immunotherapy therefore needs to be considered. Admission to an intensive-care unit, increased cerebrospinal fluid pressure, and increased NLR might be the significant factors affecting the response to first-line treatments.

Peripheral Immune Cell Ratios and Clinical Outcomes in Seropositive Autoimmune Encephalitis: A Study by the Australian Autoimmune Encephalitis Consortium

“…The optimal NLR value to predict mRS >1 was identified as 4.45 (AUC 0.866). A third retrospective study of 29 patients with anti-NMDAR encephalitis found that the median NLR was significantly higher in non-responders to first line immunotherapy than in responders, both before (4.10 vs 2.39) and after (4.14 vs 2.62) treatment ( 11 ). The results from our study support the above observations, with 1.3-fold increase in odds of treatment failure for every rise in the NLR by 1 unit.…”

“…In MS, the NLR has been demonstrated to correlate with disease progression and worse disability outcomes ( 7 – 9 ). Recent studies in AE have found that a high NLR is significantly correlated with long-term functional disability as measured by the mRS and reduced response to first line immunotherapy ( 10 , 11 ). The monocyte-to-lymphocyte (MLR) has recently been associated with disability scores in MS ( 9 ).…”

Influential Factors, Treatment and Prognosis of Autoimmune Encephalitis Patients With Poor Response to Short-Term First-Line Treatment

“…However, antibody titer was not an independent predictor of poor short-term first-line treatment response by multivariate analysis. In our previous study, we also did not find an association between the antibody titers and treatment response in anti-NMDAR encephalitis patients ( 22 ). At present, studies on the relationship between antibody titer and patients with AE are inconsistent.…”

“…Recently, studies found that NLR may be a biomarker to monitor disease progression in patients with AE ( 3 , 33 ). Our team also found that it is associated with the first-line treatment response in anti-NMDAR encephalitis ( 22 ). In this study, we found that higher NLR level was associated with non-response to short-term first-line treatment in patients with AE, and in anti-NMDAR subtype encephalitis patients.…”

“…There has been emerging evidence in the literature suggesting central hypoventilation and autonomic dysfunction were associated with disease severity and poor outcome ( 5 , 10 , 11 , 20 , 21 ). Our team also had found these symptoms were indicative of a failure to respond to first-line therapy in anti-NMDAR encephalitis ( 22 ). Combined with this study, we hypothesize that they can also be indicators for limited initial treatment response in patients with AE.…”