Even so, the actual fact that the patient initially presented acute optic neuritis associated with MOG-IgG followed by neuropsychiatric disturbance highly suggestive of autoimmune encephalitis appears to support the involvement of intermolecular epitope spreading from MOG to Caspr2 in the pathogenesis of the possible coexisting syndrome

Even so, the actual fact that the patient initially presented acute optic neuritis associated with MOG-IgG followed by neuropsychiatric disturbance highly suggestive of autoimmune encephalitis appears to support the involvement of intermolecular epitope spreading from MOG to Caspr2 in the pathogenesis of the possible coexisting syndrome. (VGKC) complex, have been documented to be associated with a novel autoimmune synaptic encephalitis with a low incidence. Herein, we reported an adult female with initial presentation of decreased vision in the right eye and subsequent episodes of neuropsychiatric disturbance including hypersomnia, agitation, apatheia, and memory impairment. Magnetic resonance imaging (MRI) revealed multiple lesions scattered in brain, brainstem, and cervical and thoracic spinal cord, showing hypointensity on T1-weighted images, hyperintensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Heterogenous patchy or ring-like enhancement was observed in the majority of lesions. The detection of low-titer MOG-IgG exclusively in cerebrospinal fluid (CSF; titer, 1:1) and Caspr2-IgG in both serum and CSF (titers, 1:100 and 1:1) led to a possible diagnosis of coexisting MOG-IgG-associated disease (MOGAD) and anti-Caspr2 antibody-associated autoimmune encephalitis. The patient was treated with immunosuppressive agents including corticosteroids and immunoglobulin, and achieved a sustained remission. To the best BMX-IN-1 of our knowledge, this is the first report on the possible coexistence of MOGAD and anti-Caspr2 antibody-associated autoimmune encephalitis, which advocates for the recommendation of a broad spectrum screening for antibodies against well-defined CNS antigens in suspected patients with autoimmune-mediated diseases of the CNS. Keywords: autoimmune, contactin-associated protein-like 2, encephalitis, MOG-IgG-associated disease, myelin oligodendrocyte glycoprotein BMX-IN-1 Introduction In the last decade, the development of antibody detection technique has remarkably expanded the knowledge on autoimmune-mediated diseases of the central nervous system (CNS). For instance, the discovery of pathogenic myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has facilitated the identification of a novel disease entity, namely MOG-IgG-associated disease (MOGAD) with the characteristic manifestations of optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, or diencephalic syndrome suggestive of demyelination.1 Similarly, antibody against contactin associated protein-like 2 (Caspr2) C a component of the voltage-gated potassium channel (VGKC) complex at the juxtaparanodal region of myelinated axons C refers to a recently recognized autoimmune encephalitis (AE) with a low incidence, and is also detected in several peripheral neurological syndromes including neuromyotonia and Morvan syndrome.2,3 Meanwhile, overlapping or coexisting syndromes have been noticeable with double or multi-antibodies targeting distinct CNS antigens such as MOG, aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), T cell-mediated cytotoxicity and B cell-mediated immune responses with complement activation.1,13 As part of VGKC complex, Caspr2 is located in the juxtaparanodal region of myelinated fibers in both CNS and peripheral nervous system (PNS), and participates in synapse synthesis and construction of central neural network.2,3,14,15 Non-complement-activating IgG4 antibodies dominate in anti-Caspr2 antibody-associated autoimmune encephalitis.10,12 Although mechanisms responsible for coexisting double or more autoantibodies are still undetermined, the phenomenon may be partially explained by the concept of epitope spreading, that is, persistent recognition and activation to self-antigens lead to chronic immune responses accompanying with the development of antibodies against diverse dominant epitopes within the same antigen (intramolecular) or to different antigens (intermolecular).5,16 Previous studies have shown epitope spreading in pediatric multiple sclerosis (MS) patients and in animal models such as experimental autoimmune encephalomyelitis (EAE) and myasthenia gravis (EAMG).17C19 Unfortunately in our case, it remains unclear whether MOG-IgG and Caspr2-IgG has emerged simultaneously or successively due to the missed testing of Caspr2-IgG at the patients local hospital. Even so, the fact that the patient initially presented acute optic neuritis associated with MOG-IgG followed by neuropsychiatric disturbance highly suggestive of autoimmune encephalitis appears to support the BMX-IN-1 involvement of intermolecular epitope spreading from MOG to Caspr2 in the pathogenesis of the possible coexisting syndrome. Further investigation is needed to verify this hypothesis. Detection of disease-specific antibodies is of crucial importance in the diagnosis of antibody-associated autoimmune disorders of the CNS. CBA has been preferentially recommended owing to its high sensitivity and specificity. Likewise in our case, positivity for Caspr2-IgG was determined by CBA with titers of 1 1:100 in serum and 1:1 in CSF, which was sufficient to make a diagnosis of anti-Caspr2 antibody-associated autoimmune encephalitis. By BMX-IN-1 contrast, MOG-IgG was detected only in the first assay with a low titer of 1 1:1 in CSF. Despite previous evidence of almost exclusive extrathecal MOG-IgG synthesis, a small minority of patients have been BMX-IN-1 THSD1 observed with exclusive MOG-IgG (titer range, 1:2C1:128) in CSF,20C22 where antibody-producing B cells could reside.