Study on clinical features and factors related to long-term outcomes of antibody-negative autoimmune encephalitis

Abstract

Objective: To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE.

Methods: Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed.

Results: In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%).

Interpretation: The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.

Figure 1

Patient Cohort. AE: autoimmune encephalitis; ANPRA: antibody‐negative probable AE; LE: autoimmune limbic encephalitis; ADEM: acute disseminated encephalomyelitis.

Figure 2

The CASE and mRS scores at three time points, namely at admission, at peak, and at the last follow‐up. A. the CASE score profiles at three time points; B. the mRS score profiles at three time points. mRS (the modified Rankin Scale); CASE (the Clinical Assessment Scale in Autoimmune Encephalitis).

Figure 3

Brain MRI findings of representative patients in each disease subtypes. A and B. The ANPRA subtype, T2 fluid‐attenuated inversion recovery (FLAIR) showed diffuse high signal intensity in the cortex; C and D. The ANPRA subtype, the bilateral symmetric lesions of the basal ganglia and thalamus; E and F. The LE subtype, T2‐FLAIR showed the bilateral hippocampal abnormal signaling; G and H. The ADEM subtype, multifocal intracranial lesions; I and J. T ADEM subtype, abnormal signals in the spinal cord.

Figure 4

Receiver operating characteristic curve for the prediction of long‐term outcomes of the RAPID scores. Poor long‐term outcomes were determined as an mRS score ≥3 at the last follow‐up. The RAPID scores in antibody‐negative AE, at admission before treatment.

Figure 5

The association of the RAPID scores with long‐term mRS in antibody‐negative AE.