To describe neurological and oncological phenotypes of AMPAR-IgG-positive patients and their co-existing neural autoantibodies.

AMPAR autoimmunity is a rare antibody-mediated neurological disorder typically manifesting with encephalitis.  A tumor is found in 60% of cases.

We retrospectively identified AMPAR-IgG-positive patients whose serum/ CSF were referred to the Mayo Clinic Neuroimmunology Laboratory (2004-2019) for neural autoantibody screening. Clinical information was extracted from Mayo Clinic records (12) or provided by referring physicians (49).

Of 101 identified patients (median age 53 years [range 15-81]; 64 female), 61 had clinical information available. Encephalopathy (75%) and seizures (30%) were the most common manifestations.  Twelve patients (20%) had AChR-IgG seropositive myasthenia gravis (MG) and thymoma; five of them lacked encephalopathy and seizures.  Brain MRIs (9 reviewed from patients with CNS manifestations) were either normal (3) or had FLAIR T2 hyperintensities, temporal (3), extratemporal (2) or both (1).  EEG was abnormal in 13/16 patients (81%) revealing epileptic discharges (3) and generalized slowing (10). CSF pleocytosis (> 5 cells/µL) was reported in 12/20 CNS cases (60%).

Neoplasia was detected in 39/61 (64 %) patients, in 18 after neurological symptoms begun. The most frequent tumors reported were thymoma (23, 91% co-existing IgGs), small-cell lung carcinoma (3), breast carcinoma (3) and ovarian teratoma (3, 2 co-existing NMDAR-IgG). Coexisting neural autoantibodies were detected in 42/61 patients (69%). The most common specificities were muscle AChR (24), CRMP5 (10), voltage-gated calcium channels (9), striational (titer>7680, 6), NMDAR (6) and GABA_BR (5). Other specificities included LGI1, Caspr2, GAD65, ANNA1, PCA1 and PCA2 autoantibodies.

Encephalopathy is the main clinical manifestation of AMPAR autoimmunity, but some paraneoplastic cases lack CNS manifestations. Thymoma was the most commonly encountered tumor in this series. Accompanying neural autoantibodies are more frequent than previously reported and the autoantibody profile is a valuable biomarker of underlying neoplasia.