Clinical analysis of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies

Abstract

Objective To explore the clinical significance of expressing multiple autoantibodies in patients with autoimmune encephalitis. Methods Cerebrospinal fluid and serum were tested in patients with undefined encephalitis admitted to Peking Union Medical College Hospital from May 2013 to December 2014. Indirect immunofluorescence test was firstly used to identify the antibodies to neuronal cell-surface or synaptic receptors (including N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), leucine-rich glioma inactivated protein 1 (LGI1), and gamma-aminobutyric acid beta receptor (GABABR)). In those patients with positive antibodies, antibodies against intracellular neuronal antigens associated with paraneoplastic neurological symptoms were tested. Anti-aquaporin protein-4(AQP4) antibody was tested depending on patients' clinical manifestations. Results Ten patients were detected combined with additional autoantibodies in 531 patients with positive antibodies related to autoimmune encephalitis. Anti-Hu antibody was positive in 5 patients with anti-GABABR encephalitis, in 1 of whom anti-NMDAR antibody was also identified; anti-AQP4 antibody was positive in 1 patient with relapsing anti-NMDAR encephalitis; anti-CASPR2 and anti-Yo antibodies were respectively positive in 2 patients with anti-LGI1 encephalitis; anti-CV2 and anti-Hu antibodies were respectively positive in 2 patients with anti-AMPAR encephalitis. Clinical presentation of all cases was consistent with typical encephalitis or limbic encephalitis. Brain stem was involved in 3 patients. Peripheral sensory neuropathy was present in 1 patient, while myalgia and fasciculation were present in 1 patient. Seven patients responded well to the immunotherapy. Tumors were pathologically or radiologically confirmed in 7 cases, including lung cancer in 5 cases, suspected thymoma in 1 case and highly suspected mediastinal tumor without pathological identification in 1 case. Conclusions Due to the pathological mechanism, co-existence of multiple autoantibodies affects clinical manifestations of patients and results in variation and overlap of them. The additional positivity of onconeuronal antibodies directs the search for occult tumor. Key words: Encephalitis; Autoimmune diseases of the nervous system; Autoantibodies; Receptors, N-methyl-D-aspartate; Receptors, GABA