Performance of cryptogenic new onset refractory status epilepticus score in a Brazilian cohort after testing for antineuronal antibodies with tissue-based and cell-based assays

Abstract

Objective: This study was undertaken to describe a case series of Brazilian new onset refractory status epilepticus (NORSE) patients and evaluate the sensitivity and specificity of a clinical score to predict cryptogenic etiology (c-NORSE score) after autoimmune encephalitis (AE) testing.

Methods: Thirty-seven patients with NORSE from the Brazilian Autoimmune Encephalitis Network were investigated with brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and complementary testing with tissue-based assays and cell-based assays for antineuronal and antiglial antibodies (abs) in serum/CSF. Final diagnoses were compiled after chart review. Patients were allocated into two groups according to c-NORSE score: (≥5) high score (HS) or (<5) low score (LS), and clinical variables were compared. c-NORSE score sensitivity and specificity were calculated.

Results: We found that 23 (62%) of the NORSE patients were children, 49% were female, 22% had AE, and 51% were classified as c-NORSE. Eleven patients (30%) were allocated to the HS group and 26 (70%) to LS. Bilateral and symmetric MRI findings were more frequent in the HS group (HS 100% vs. LS 43%, p = .018), whereas memory or behavioral symptoms were less common (HS 27% vs. LS 89%, p = .001). All HS patients had c-NORSE, whereas 69% of the LS patients had other diagnoses, such as AE (n = 8), herpes simplex virus encephalitis (n = 4), paraneoplastic encephalomyelitis (n = 1), acute disseminated encephalomyelitis (n = 1), and other causes (n = 4). The sensitivity of the c-NORSE score for predicting cryptogenic cases was 57.9% (95% confidence interval [CI] = 36%-80%), and the specificity was 100% (95% CI = 84%-100%).

Significance: In this cohort, AE was the most identified cause of NORSE, and 51% were cryptogenic. c-NORSE score ≥ 5 had a specificity of 100% (95% CI = 84%-100%) for identifying cryptogenic cases, whereas a score < 5 indicates additional investigation should be ordered. Although the sensitivity of the c-NORSE score was lower than previously reported, suggesting it may vary depending on complementary investigation, it is a useful tool for bedside NORSE evaluation in low-income countries, where access to antineuronal abs is limited.

Keywords: autoimmune encephalitis; c‐NORSE score; epilepsy; febrile infection‐related epilepsy syndrome; new onset refractory status epilepticus; status epilepticus.