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.

FIGURE 1

Flowchart of new onset refractory status epilepticus (NORSE) patient selection and cryptogenic NORSE (c‐NORSE) score calculation. Of 451 referred patients, 370 were excluded. Among 81 with status epilepticus (SE) and refractory SE (RSE), 40 were selected after further screening and divided into high and low c‐NORSE score groups. abs, antibodies; ADEM, acute disseminated encephalomyelitis; AE, autoimmune encephalitis; GAD65, glutamic acid decarboxylase 65; HSV, herpes simplex virus; MOG, myelin oligodendrocyte glycoprotein; NMDAR, N‐methyl‐D‐aspartate receptor.