Abstract
ObjectiveTo establish the diagnostic biomarker of electroencephalogram (EEG) to distinguish between anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) and other types of autoimmune encephalitis (other AEs).MethodsWe reviewed the clinical records of 90 patients with acute encephalitis who were treated in our institution between January 2014 and October 2020. We enrolled the patients who fulfilled the diagnostic criteria for possible AE (pAE) defined by Graus et al. (pAE criteria) and then classified into definite NMDARE and other AEs. We investigated the main syndrome and analyzed all admission EEGs using EEG power value (PV). Statistical significance was tested using the Mann–Whitney U test or Fisher’s exact test.ResultsTwenty-five patients fulfilled the pAE criteria and were classified into 9 with definite NMDARE (median age: 21 years; 8 women) and 12 with other AEs (median age: 37.5 years; 6 women). Four were eventually excluded. Speech dysfunction (9/9 vs. 4/12, p = 0.005) and movement disorders (6/9 vs. 1/12, p = 0.016) were more frequent in NMDARE than in other AEs. The PV analyses revealed the novel quantitative EEG (qEEG) index, namely, fast slow ratio (FSR) (PV of total beta/PV of total theta + delta). The median FSR (0.139 vs. 0.029, p = 0.004) was higher for NMDARE than other AEs, and the receiver operating characteristic curve area of FSR was 0.86 (95% CI 0.70–1.00). A cutoff value of 0.047 yielded a specificity of 0.75 and a sensitivity of 1.00. Focusing on patients who did not meet the “probable NMDARE criteria” in Graus 2016 (proNMDARE criteria) (n = 10), the pretest probability of NMDAR antibody test was 0.30 (3/10), which increased in patients with an FSR greater than the cutoff (n = 5) to 0.60 (3/5).ConclusionsThe NMDARE group highlighted speech dysfunction and movement disorders, and a novel qEEG index FSR accurately distinguished the NMDARE patients from other AEs. The FSR is a promising diagnostic marker for NMDARE that indicates the positive results of NMDAR antibodies in patients with AE when combined with the proNMDARE criteria.
Highlights
Antibodies against anti-N-methyl-d-aspartate receptor (NMDAR) trigger anti-N-methyl-d-aspartate receptor encephalitis (NMDARE), a well-characterized autoimmune encephalitis (AE) whose features include psychiatric symptoms, seizures, decreased level of consciousness, movement disorders, autonomic disabilities, and hypoventilation [1, 2]
We evaluated how helpful a novel quantitative EEG (qEEG) index fast slow ratio (FSR) is to distinguish NMDARE from other AEs when compared to the criteria of “probable NMDARE” described by Graus [4]
The patients were classified into 9 with NMDARE and 12 with other AEs, who were classified into six categories of AE according to Graus criteria [4] (Figure 1)
Summary
Antibodies against anti-N-methyl-d-aspartate receptor (NMDAR) trigger anti-N-methyl-d-aspartate receptor encephalitis (NMDARE), a well-characterized autoimmune encephalitis (AE) whose features include psychiatric symptoms, seizures, decreased level of consciousness, movement disorders, autonomic disabilities, and hypoventilation [1, 2]. Graus et al developed syndrome-based diagnostic criteria of probable NMDARE (proNMDARE) available without any antibody test [4], but their sensitivity was deemed unsatisfactory in the first 2 weeks of disease onset [5]. These limitations prompted researchers to explore diagnostic biomarkers that distinguished NMDARE from other types of AE (other AEs) in early stages, including CSF cytokines, 18F-FDG PET, resting-state functional magnetic resonance imaging (MRI), and electroencephalogram (EEG) [6]. Other EEG characteristics on NMDARE such as excessive beta activity and generalized rhythmic delta activity (GRDA) were reported [8] These features could be used to non-invasively distinguish NMDARE from other AEs, though the sensitivity of EDB is approximately 30% as described in the first report [7]
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