Clinical characteristics and outcome of patients with autoimmune encephalitis: clues for paraneoplastic aetiology.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AE) represents a complex syndrome with diverse clinical manifestations and therapeutic outcomes. The aim of this study was to report the clinical characteristics and the long-term outcome of patients with paraneoplastic and idiopathic AE. METHODS: All patients with subacute encephalopathy admitted to the Neurology Department of our Institution from January 2012 to May 2019 were consecutively enrolled. Patients' serum and cerebrospinal fluid were tested for neural-specific autoantibodies by indirect immunofluorescence assays on mouse brain, rat neurons, cell-based assays and immunoblots. Outcome was assessed by the modified Rankin Scale score. RESULTS: From 107 adult patients with subacute encephalopathy, 50 patients were finally diagnosed with AE. Neural antibodies (Abs) were detected in 45/50 patients (90%). Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent (6/50, 12%) Ab specific to neural surface antigens detected in adults with AE. Paraneoplastic encephalitis was diagnosed in 16/50 patients (32%). The presence of bilateral temporal lobe lesions on magnetic resonance imaging and cerebrospinal fluid restricted oligoclonal bands was associated with a higher probability to detect cancer at the time of AE diagnosis. All patients with Abs to neural surface antigens had a good outcome at last follow-up. Severe disability at AE onset and the lack of long-term immunosuppression predicted a poor outcome. CONCLUSIONS: Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent Ab detected. Patients with bilateral temporal lobe lesions and oligoclonal bands have a higher probability to harbour an occult tumour. In these patients, a strict surveillance and monitoring for cancer detection is recommended.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: 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. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a 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 defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor 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%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus 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 were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient 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 patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.