Simple and effective serum biomarkers potential for predicting status epilepticus in anti-N-methyl-D-aspartate receptor encephalitis

Abstract

Background: Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis who also present with status epilepticus (SE) often have a poor prognosis. The aim of this study is to explore simple and effective predictors for anti-NMDAR encephalitis accompanied with SE.

Methods: We retrospectively analyzed 65 anti-NMDAR encephalitis patients from January 2015 to December 2018 who admitted to the Third Affiliated Hospital of Sun Yat-sen University. Patients were divided into SE group and non-SE groups. Their pre-treatment data and 3-month follow-up data were retrospectively analyzed.

Results: The results showed that compared with the non-SE group, the levels of serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) in anti-NMDAR encephalitis patients with SE decreased significantly before treatment. Additionally, the levels of serum UA and HDL-C increased while the level of C-reactive protein (CRP) decreased 3 months after treatment in the SE group. Compared with the non-SE group, the SE patients had higher modified Rankin scale (mRS) scores before (mRS1) and after treatment (mRS2). Serum UA concentrations before treatment showed significantly negative correlations with mRS1 (r = - 0.407, p < 0.01) and mRS2 (r = - 0.458, p < 0.001), while the level of serum CRP before treatment had strong positive correlations with mRS1 (r = 0.304, p < 0.05) and mRS2 (r = 0.301, p < 0.05) in anti-NMDAR encephalitis patients. The receiver operating characteristic curve demonstrated that the combined detection of UA, HDL-C and CRP before treatment had a significantly higher value (the area under the curve = 0.848; 95% confidence interval [CI], 0.74-0.957; p < 0.001) to predict anti-NMDAR encephalitis accompanied with SE than that of single detection.

Conclusions: Hence, the combined detection of serum UA, HDL-C and CRP before treatment may be simple and effective indicators for predicting SE in anti-NMDAR encephalitis, which may be helpful in early stages to remind clinicians to be alert to the emergence of SE.

Keywords: Anti-N-methyl-D-aspartate receptor encephalitis; Combined detection; Predictor; Status epilepticus.

Fig. 1

(A) Abnormal MRI signaling of one 28-year-old woman patient from the anti-NMDAR encephalitis with non-SE group. The brain MRI showed swelling and T2 FLAIR slightly hyperintensity in the bilateral temporal lobes. (a, b) T2-weighted MRI, (c, d) Axial T2 FLAIR sequences. MRI, magnetic resonance imaging; FLAIR, fluid attenuated inversion recovery; non-SE, non-status epilepticus; anti-NMDAR, anti-N-methyl-D-aspartate receptor. (B) A representative EEG of the anti-NMDAR encephalitis patients with SE. High frequency beta activity in the left central and parietal lobe with progressively increasing amplitude, typical of the tonic phase in status epilepticus, was associated in this patient with dystonic posturing of his right arm (a and b are continuous records). anti-NMDAR, anti-N-methyl-D-aspartate receptor; SE, status epilepticus

Fig. 2

Comparison of serum UA, HDL-C and CRP before treatment among healthy controls, non-SE and SE anti-NMDAR encephalitis patients. p < 0.05 was considered significant. A uric acid; B high density lipoprotein cholesterol; C C-reactive protein. Non-SE, non-status epilepticus; SE, status epilepticus; anti-NMDAR, anti-N-methyl-D-aspartate receptor; UA, uric acid; HDL-C, high density lipoprotein cholesterol; CRP, C-reactive protein

Fig. 3

Comparison of mRS scores before treatment, after treatment and improved between non-SE and SE anti-NMDAR encephalitis patients. p < 0.05 was considered as significant. A mRS scores before treatment; B mRS scores after treatment; C mRS scores improved. The improved mRS scores was the change of mRS scores after treatment compared with before treatment. Non-SE, non-status epilepticus; SE, status epilepticus; anti-NMDAR, anti-N-methyl-D-aspartate receptor; mRS, modified Rankin scale

Fig. 4

Correlation between serologic markers before treatment and mRS scores of anti-NMDAR encephalitis patients. p < 0.05 was considered significant. A negative correlation between UA and mRS scores before treatment (mRS1)(r = − 0.407, p < 0.01); B negative correlation between UA and mRS scores after treatment (mRS2) (r = − 0.458, p < 0.001); C correlation between HDL-C and mRS1(r = − 0.089, p > 0.05); D correlation between HDL-C and mRS2(r = − 0.030, p > 0.05); E positive correlation between CRP and mRS1(r = 0.304, p < 0.05); F positive correlation between CRP and mRS2(r = 0.301, p < 0.05). mRS, modified Rankin scale; mRS1, mRS scores before treatment; mRS2, mRS scores after treatment; anti-NMDAR, anti-N-methyl-D-aspartate receptor; UA, uric acid; HDL-C, high density lipoprotein cholesterol; CRP, C-reactive protein

Fig. 5

The receiver operating characteristic (ROC) analysis for models predicting SE in anti-NMDAR encephalitis. Combined UA, HDL-C and CRP levels before treatment exhibited the largest AUC (0.848) of the serologic parameters that were investigated, revealed had good value in distinguishing SE from non-SE. ROC, receiver operating characteristic; SE, status epilepticus; non-SE, non-status epilepticus; anti-NMDAR, anti-N-methyl-D-aspartate receptor; UA, uric acid; HDL-C, high density lipoprotein cholesterol; CRP, C-reactive protein; AUC, area under the ROC curve. ROC curve analysis