Abstract
ObjectiveTo comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes.MethodsA retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF.ResultsPatients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05).ConclusionsPatients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.
Highlights
Anti–N-methyl-D-aspartate receptor encephalitis is a major type of autoimmune encephalitis with more than 1000 reported cases since the discovery of autoantibodies against the NMDAR1 subunit (NR1) subunit of the NMDA receptor in 2007 [9, 24]
Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE
Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE
Summary
Anti–N-methyl-D-aspartate receptor encephalitis (antiNMDARE) is a major type of autoimmune encephalitis with more than 1000 reported cases since the discovery of autoantibodies against the NR1 subunit of the NMDA receptor in 2007 [9, 24]. In 4106 cases of encephalitis of unidentified aetiology in China, 423 cases (10.3%) were positive for anti-NMDAR antibodies [12]. Especially ovarian teratomas, exist in 38–59% of cases with anti-NMDARE in western countries [8, 19]. In China, ovarian teratomas were observed in 8% of all patients and 26.9% of women with anti-NMDARE [6, 22]. It has been suggested that anti-NMDAR antibodies were directed against neuronal cell surface antigens of specific tumor cell populations, i.e. dysplastic neurons, triggering the onset of anti-NMDARE with severe neurological symptoms following CNS distribution via cerebrospinal fluid (CSF) [7]. Our current study aimed to explore the relationship between teratomas and anti-NMDARE by systematically reviewing pathology, clinical features, and inflammatory cytokines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
