Co-expression of NMDA-receptor subunits NR1, NR2A, and NR2B in dysplastic neurons of teratomas in patients with paraneoplastic NMDA-receptor-encephalitis: a retrospective clinico-pathology study of 159 patients

Jiang, Xinyue; Song, Lei; Zhang, Le; Xu, Lei; Lin, Mintao; Blümcke, Ingmar; Piao, Yue-Shan; Zhou, Dong

doi:10.1186/s40478-020-00999-2

Cited by 19 publications

(33 citation statements)

References 24 publications

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“…The LOS was significantly positively associated with total direct cost ( r = .835) in our study, in agreement with previous studies 26,40 . The ICU admission rate in our study (5.2%) was lower than that in our previous studies of autoimmune encephalitis (10.7%–12.6%) 26,41,42 . Additionally, only 35.1% of the patients in our cohort received the standard HRZE regimen, consistent with the study conducted among neurologists (42.7%) in India, 22 and 50.6% of the patients received other intensified regimens with levofloxacin or moxifloxacin in our study.…”

Section: Discussionsupporting

confidence: 92%

Direct economic burden of patients with tuberculous meningitis in western China

Zhou

Yang

2021

Acta Neurol Scand

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Objective To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. Methods Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long‐term outcomes. The patients were followed up for 15–53 months. We performed a cost‐of‐illness study and analyzed the cost contributors with a generalized linear model. Results In total, the cases of 154 TBM patients (95 males, 59 females, aged 14–82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822–67,285), with a mean direct medical cost of USD 8,901 (range 1,189–67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845–52,921) and USD 1,967 (range 0–60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33–3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6–152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0–2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long‐term outcome. Conclusions Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

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Section: Discussionsupporting

confidence: 92%

Direct economic burden of patients with tuberculous meningitis in western China

Zhou

Yang

2021

Acta Neurol Scand

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“…Remarkably, less frequent CD8 + T cells (T C ) were reported on brain biopsy or autopsy in patients with ovarian teratoma and anti-NMDAR encephalitis [27,59]; thus, we inferred the less production of T C at TLS and circulation in the bloodstream. Nonetheless, CD20 + B cells were more frequent in the teratomarelated anti-NMDAR encephalitis than in the controls (p = 0.001), suggesting a presiding humoral immune environment in those teratomas [52]. In addition, as shown in human autopsies, complement-mediated mechanisms were unrelated to the pathogenesis of teratoma-associated anti-NMDAR encephalitis [27,59,60].…”

Section: The Microenvironment Involving In Ovarian Teratomas With Anti-nmdar Encephalitismentioning

confidence: 88%

“…However, the headstream triggers and disease association with ovarian teratoma were those we wanted to clarify. Two confirmed triggers of anti-NMDAR encephalitis were (1) tumors, which were primarily ovarian teratomas (with penetrance reported to be 94%) [8,28,52], and (2) postviral events, such as herpes simplex encephalitis [53,54]. This section specifically discussed the linkage between anti-NMDAR encephalitis and ovarian teratoma for a comprehensive understanding and increasing recognition.…”

Section: The Triggers and Peculiar Cell Composition In The Ovarian Teratomas With Anti-nmdar Encephalitismentioning

confidence: 99%

“…Consequently, a spectrum of damage ranging from varying degrees of degenerative changes to cell loss could be expected in anti-NMDAR encephalitis-related ovarian teratomas [56]. In addition, Jiang et al observed that anti-NMDAR encephalitisrelated ovarian teratomas showed more dysmorphic neurons with irregular cell shape and giant nuclei than those without encephalitis [52], suggesting that those dysplastic neurons being a potential source of auto-antigens could trigger anti-NMDAR encephalitis. Ovarian teratomas have a cellular composition of teratoma tumors cells, some sporadic neuroglial cells, and inflammatory infiltrates as well as a tertiary lymphoid structure (TLS) with the germinal center.…”

Section: The Triggers and Peculiar Cell Composition In The Ovarian Teratomas With Anti-nmdar Encephalitismentioning

confidence: 99%

“…One potential explanation was that the immune and inflammatory response in patients with ovarian teratoma and anti-NMDAR encephalitis might damage the integrity of capillaries and lead to the dysfunction of BBB [65]. Notably, Jiang et al showed increasing levels of TNF-α, IL-10, and GM-CSF in patients with teratoma-related anti-NMDAR encephalitis compared to the control group, indicating the involvement of the inflammation process in the pathogenesis [52]. Moreover, the rising levels of GM-CSF not only up-regulated the production of pro-inflammatory cytokines but also formed positive feedback to activate microglial cells in the CNS, producing highly neurotoxic substances that might damage the coherence of BBB [65,66].…”

Section: The Association With Teratoma-related Anti-nmdar Encephalitis and Blood-brain Barrier Integritymentioning

confidence: 99%

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The Association of Ovarian Teratoma and Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Updated Integrative Review

Chen

2021

IJMS

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Ovarian teratomas are by far the most common ovarian germ cell tumor. Most teratomas are benign unless a somatic transformation occurs. The designation of teratoma refers to a neoplasm that differentiates toward somatic-type cell populations. Recent research shows a striking association between ovarian teratomas and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a rare and understudied paraneoplastic neurological syndrome (PNS). Among teratomas, mature teratomas are thought to have a greater relevance with those neurological impairments. PNS is described as a neurologic deficit triggered by an underlying remote tumor, whereas anti-NMDAR encephalitis is characterized by a complex neuropsychiatric syndrome and the presence of autoantibodies in cerebral spinal fluid against the GluN1 subunit of the NMDAR. This review aims to summarize recent reports on the association between anti-NMDAR encephalitis and ovarian teratoma. In particular, the molecular pathway of pathogenesis and the updated mechanism and disease models would be discussed. We hope to provide an in-depth review of this issue and, therefore, to better understand its epidemiology, diagnostic approach, and treatment strategies.

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