Abnormal Brain MRI in Anti-NMDA Receptor Encephalitis: Clinical and Prognostic Implications

Abstract

Background and objectives: Abnormal brain MRI is associated with poor outcomes in anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). We aimed to characterize the lesions on brain MRI in NMDARE and to assess the clinical and prognostic associations.

Methods: This retrospective cohort study included patients with NMDARE identified at the French Reference Center for Autoimmune Encephalitis, with at least a one-year follow-up, and with available brain MRI results. In case of brain extralimbic lesion, the image files were reviewed when available. Clinical data were collected from medical records. Multivariable logistic regression analysis was used to study the outcomes at 2-year follow-up; recovery was defined as modified Rankin Scale score ≤1.

Results: Among the 255 patients included, 37 (14.5%) had limbic hyperintensities and 41 (16.1%) had extralimbic lesions that included multiple sclerosis (MS)-like lesions (14/41, 34.1%); extensive lesions (5/41, 12.2%); and poorly demarcated fluffy lesions, either multifocal (10/41, 24.4%) or involving the cerebral cortex or cerebellum (6/41 each, 14.6%). Extralimbic lesions coexisting with limbic lesions (19/41 patients, 46.3%) were mostly fluffy lesions (11/19, 57.9%). Ten patients had overlapping demyelinating syndromes: 4 with MS, 4 with myelin oligodendrocyte glycoprotein-associated disorder, and 2 with neuromyelitis optica spectrum disorder; all had MS-like (7/10 patients) or extensive (3/10 patients) lesions, and none had fluffy lesions. Extralimbic lesions were associated with symptoms nontypical for NMDARE (23/41, 56.1%, p < 0.001), especially cerebellar ataxia (17/41, 41.5%) and motor impairment (12/41, 29.3%). At 2 years, patients with MS-like or extensive lesions had a lower recovery rate (5/12, 41.7%, and 1/4, 25%, respectively) compared with the patients without extralimbic lesions (124/162, 76.5%; p = 0.014 and p = 0.047, respectively). In multivariable analysis, MS-like lesions, but not hippocampal nor fluffy lesions, were associated with absence of recovery at 2 years (adjusted OR 0.1, 95% CI 0.03-0.42, p = 0.002; extensive lesions [n = 4] not included in the analysis).

Discussion: Brain MRI lesions in NMDARE include limbic hyperintensities and 3 patterns of extralimbic lesions, which are associated with nontypical NMDARE symptoms. Moreover, MS-like and extensive lesions, but not fluffy nor hippocampal lesions, are associated with overlapping demyelinating syndromes and poor clinical outcomes at 2 years. These findings can have practical implications on the monitoring of patients with NMDARE.

Figure 1. Flowchart of the Study

NMDARE = anti-N-methyl-d-aspartate receptor encephalitis.

Figure 2. Representative Images of the Extralimbic Lesions in NMDARE

Representative images of MS-like (A and B) and extensive FLAIR (C) lesions in patients with NMDARE overlapping with MS (A.a), myelin oligodendrocyte glycoprotein–associated disorder (MOGAD) (B.a), or NMOSD (C.a), and representative image of a fluffy lesion (D.a). Follow-up shows stable lesion load in the patient with MS (A.b; 6-month interval from A.a) and regression of the lesions in the patient with MOGAD (B.b, 7 months from B.a) and in the patient with NMOSD (C.b; 3 years from C.a), as well as of the fluffy lesion (D.b, 3 months from D.a). FLAIR = fluid-attenuated inversion recovery; MOGAD = myelin oligodendrocyte glycoprotein–associated disorder; NMDARE = anti-N-methyl-d-aspartate receptor encephalitis; NMOSD = neuromyelitis optica spectrum disorder.

Figure 3. Prognostic Factors of Recovery of Patients With NMDARE Identified by Multivariable Logistic Regression Analysis

The presence of MS-like lesions, CSF cellularity above 20/µL, and decreased consciousness were independently associated with decreased odds of recovery at 2 years. Conversely, age younger than 45 years increased the odds of recovery while hippocampal hyperintensities and fluffy lesions had no effect on the 2-year outcomes. Extensive FLAIR lesions were not included in the model because of the small number of patients (n = 4). Only the 197 patients with at least 2 years of follow-up were included. FLAIR = fluid-attenuated inversion recovery; NMDARE = anti-N-methyl-d-aspartate receptor encephalitis; WBC = white blood cell.