Subgroup Comparison According to Clinical Phenotype and Serostatus in Autoimmune Encephalitis: A Multicenter Retrospective Study

BACKGROUND: Autoimmune encephalitides (AE) include a spectrum of neurological disorders, whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. We studied AE-DC impact on patients' management, focusing on the subgroup of Ab-negative-AE. METHODS: Retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based-assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures), that contributed to define final categories. Patients were classified as Ab-positive-AE [NMDAR-encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE], or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118(59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). One-hundred-eighteen patients fulfilled AE-DC, 81(68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, 9), 37(31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive- vs Ab-negative-LE. Twenty-four/118(20.3%) patients had tumors, and 19/118(16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (p=0.045), responded more frequently to treatments (92.3% vs 65.6%, p<0.001), and received second-line therapies more often (33.3% vs 10.8%, p=0.01). Delays in first-line therapy initiation associated with poor response (p=0.022; OR,1.02; CI,1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection, allowing better patients' management, but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE share similar oncologic profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.