Introduction
Autoimmune encephalitis (AE) is an immunopathologic encephalopathy mediated by auto-antibodies. Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common AE following N-methyl-d-aspartate (NMDA) receptor encephalitis, and is characterized by rapidly progressive dementia (RPD), faciobrachial dystonic seizures (FBDS), hyponatremia, and T2 hyperintensity of bilateral hippocampus on magnetic resonance imaging (MRI)[1]. The diagnosis of AE is challenging because of heterogeneous clinical presentation especially early in the course of disease[2]. A large multicenter study of AE indicated that “typical” clinical features above were absent in a relatively large segment of cases: only 42% presented with RPD; only 47% suffered from FBDS; 35% had no hyponatremia and 26% showed normal structural MRI[3]. Therefore, anti-LGI1 encephalitis was commonly misdiagnosed as its mimickers, including Creutzfeldt-Jakob disease (CJD)[4], herpes simplex encephalitis[5], Hashimoto’s encephalopathy[6], neurodegenerative disease[7] and stroke[8].
In the past few years, many researches have indicated correlations between the presence of tumors and paraneoplastic limbic encephalitis (PLE), an important subtype of AE. One study of the correlation of PLE and tumor found that among 50 patients diagnosed with PLE, cancer of lung (50%, of which small-cell lung cancer (SCLC) accounted for 80%), testis (20%) and breast (8%) were the three most common tumors, alongside other rarer cancers like Hodgkin’s disease (4%), ovarian teratoma (4%) and thymoma (2%)[9]. PLE is thought to be due to stimulation of an antibody-mediated immune response caused by tumor antigens that are cross-reactive with neural host antigens[10]. The most specific correlation is between anti-NMDAR encephalitis and ovarian teratoma[9]. In a descriptive clinical report including 81 patients with anti-NMDAR encephalitis, ovarian teratoma was found in 56% of patients > 18 years old, 31% of patients > 14 and < or = 18 years old and 9% of patients < or = 14 years old. No tumors were found in male patients[11]. However, the prevalence of tumor in voltage-gated potassium Channel (VGKC) encephalitis (including LGI1 or contactin-associated protein 2(Casper2)) was less than 10%[12], being more frequently seen in Casper2 encephalitis than in anti-LGI1 encephalitis [12]. In one study, less than 10% anti-LGI1 encephalitis was comorbid with tumors, including thymus, thyroid, lung and renal cell tumors[13, 14]. Even though tumors were detected in 13% of a series of 166 patients with LGI1 IgG positivity [15], to our best knowledge, no correlation between teratoma and LGI encephalitis has been reported to date.
Therefore, here we report a case of anti-LGI1 encephalitis comorbid with ovarian teratoma; pathological association was indicated by immunohistochemistry showing partial or focal positive nuclear staining of LGI1 was appreciated in some tumor cells. The patient has been followed for 5 months since diagnosis in clinic, with neuropsychological evaluations, neuroimaging, electroencephalography (EEG) and serum antibody titers. The clinical features of a series of anti-LGI1 encephalitis cases without ovarian teratoma were also summarized and compared with this rare case to explore the possible diagnostic clues to anti-LGI1 encephalitis with and without teratoma.
Materials and Methods