Anti-NMDA Receptor Encephalitis: Clinical Features and Basic Mechanisms

Lynch, David R.; Rattelle, Amy; Dong, Yi; Roslin, Kylie; Gleichman, Amy J.; Panzer, Jessica A.

doi:10.1016/bs.apha.2017.08.005

Cited by 73 publications

(74 citation statements)

References 107 publications

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“…One hypothesis for explaining the anti-NMDAR clinical features is that psychiatric symptom which is more common in adults is caused by NMDAR hypofunction resulted from antibody mediated NMDAR internalized, while neurological symptoms like seizures and movement disorders as initial symptoms are caused by agonist effect of NMDAR, extrasynaptic NMDAR hyperfunction or neuronal network imbalance with impaired intraneuronal activity [6,1]. Extrasynaptic NMDAR is more commonly in GluN1/2B, while synaptic NMDAR is more commonly in GluN1/2A [6]. And during development from juvenile to adult, NMDAR subunit switch from GluN2B to GluN2A [22].…”

Section: Discussionmentioning

confidence: 99%

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Pediatric Anti-NMDAR Encephalitis in Southern China: Analysis of 107 Cases

Hou

et al. 2020

Preprint

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Background: Research on pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is limited. We studied clinical features of children with anti-NMDAR encephalitis in southern China.Methods: Pediatric anti-NMDAR encephalitis between 2014 and 2019 from one tertiary medical center was analyzed. The Modified Rankin Scale (mRS) score was adopted to evaluate outcomes.Results: 107 children (M/F=50/57; mean onset age=6.3 y) with anti-NMDAR encephalitis were involved. Boys significantly showed earlier onset age, higher ratio of fever, longer hospital day, more courses of steroid treatment, higher mRS score after treatment. 48.6% of patients had prodromal events with infectious events most common. The most common symptom at onset and during whole course was seizures and psychiatric symptoms respectively. Initial median white cell count of cerebral spinal fluid (CSF) was 22.0x106/L. 12.1% of patients had positive herpes simplex virus DNA of CSF. All patients had CSF positive NMDAR antibodies, although 86.9% of patients had serologically positive. 9.3% of patients had overlapped other neuronal antibodies. Electroencephalograph showed abnormalities with slow wave (95.3%) and epileptic activity (41.5%). Delta brush was revealed in 3.8% of patients. 36.4% of patients had lesions in brain MRI, with local lesions most common. No tumor was found in all. 84.9% of patients responded well to the first line therapy (steroid plus immunoglobulin), while 12 patients accepted second-line therapy (Rituximab) with 91.7% of effective rate. 12.1% of patients relapsed. 2 male patients died. The median length of hospital stay was 28 days. The mRS score was significantly improved after treatment. 51.0% of patients had a full recovery. 76.6% of patients had mild neurological disability (mRS≤2). Male, speech disorder, initial score of mRS and administration of second-line therapy were independent risk factors associated with the outcome.Conclusions: Of pediatric anti-NMDAR encephalitis in southern China: the mean onset age was about 6-year-old, earlier in boys; boys remained slower to recover and with a worse prognosis; the most common respective symptom at onset and during whole course was seizures and psychiatric symptoms; combination with tumor was rare; most patients respond well to the immunotherapy; relapse and fatality rate were relatively low; most patients had a good prognosis.

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Section: Discussionmentioning

confidence: 99%

“…Majority of these manifestations resemble those in NMDAR hypofunction caused by NMDAR antagonists. NMDAR hypofunction caused by antibody mediated NMDAR internalized is a popular hypothesis for the mechanism of anti-NMDAR encephalitis [1,6]. But this hypothesis is insu cient to explain some core symptoms like seizures [1,6].…”

Section: Introductionmentioning

confidence: 99%

Pediatric Anti-NMDAR Encephalitis in Southern China: Analysis of 107 Cases

Hou

et al. 2020

Preprint

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“…The most representative and high-incidence subtype of AE associated with teratoma was NMDA encephalitis; NMDA receptor-expressing neurons have been described in the neural tissue within teratoma, which was pathogenetic of NMDA encephalitis [25]. Unlike NMDA receptors, which are the extracellular domain of the GluN1 subunit [26], LGI1 is not a structural component of a receptor or ion channel, but is rather secreted by neurons, perhaps explaining why the incidence of tumor is much lower in LGI1 encephalitis compared with NMDA encephalitis. Nevertheless, LGI1 forms a trans-synaptic complex with presynaptic proteins and is involved in synaptic transmission of neuronal excitability [27], so LGI1 encephalitis may still be comorbid with tumors such as teratoma.…”

Section: Discussionmentioning

confidence: 99%

What’s Different about Teratoma-Associated LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series

Li¹,

Cai²,

Xu³

et al. 2020

Preprint

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Background Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. The aim of this study is to report a case of teratoma-associated LGI1 encephalitis, to summarize a retrospective series of LGI1 encephalitis and compare them. Methods Clinical data for 10 people with LGI1 encephalitis were collected. Patients were divided into those with and without associated teratoma, and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical (IHC) assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. Results The LGl1 patient with teratoma was similar to the non-teratoma (NT) group in many ways: age at onset (average 47.3 in NT group); percent presenting with rapidly progressive dementia (RPD) (67% of NT group) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (MRI) (44%); diffuse slow waves on electroencephalography (EEG) (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the NT group. Teratoma pathology was characterized by mostly thyroid tissue and IHC assay confirmed positive LGI1 expression. Conclusion In our series, LGI1 encephalitis included common clinical features: RPD, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, T2-MRI hyperintensity of hippocampus and residual cognitive deficit. We observed some differences in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

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“…Those who continued to be treated with tocilizumab after initial treatment failure may have shown a better prognosis at follow-up after 24 months [61]. Although most current studies on the prognosis of anti-NDMAR encephalitis demonstrate immunotherapy to be efficacious and able to gradually restore patients to baseline levels, current research has gradually progressed toward addressing patients who have not fully recovered [62]. More research is needed to understand the sequelae following immunotherapy in anti-NDMAR encephalitis patients.…”

Section: Immunotherapymentioning

confidence: 99%

“…Most tumors in men are germ cell tumors, and only 5% of male anti-NMDAR encephalitis patients over 18 years of age have underlying tumors [63]. In addition, liver neuroendocrine tumors, uterine neuroendocrine tumors, small cell lung cancer, and cancers of unknown origin have recently been associated to anti-NDMAR encephalitis [62]. In these cases, tumor resection in conjunction with simultaneous immunotherapy can significantly accelerate the amelioration of the disease and reduce the need for second-line treatments [63].…”

Section: Tumor Treatmentmentioning

confidence: 99%

Current Progress on Assessing the Prognosis for Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis

Wang

Xiao

2020

BioMed Research International

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Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antineuronal antibody encephalitis in autoimmune encephalitis found at present. It has complex clinical manifestations such as psychiatric and behavioral abnormalities, seizures, movement disorders, consciousness, and autonomic dysfunction. The relationship between those manifestations and prognosis is unclear. Electroencephalography (EEG) is gradually becoming useful in the evaluation of the prognosis of anti-NMDAR encephalitis patients, while imaging and antibody testing have a limited prognostic value. Starting the patients on adequate treatments (such as immunotherapy) in a timely fashion has a positive impact on their prognosis. Nevertheless, research on the prognosis of anti-NMDAR encephalitis remains scarce. Here, we review the current advances of prognosis-related research from the clinical manifestations of the disease and auxiliary examinations such as EEG, magnetic resonance imaging (MRI), 18F fluorodeoxyglucose positron emission tomography (FDG-PET), and antibody measurement. In addition, we also discuss the impact of different treatment options on prognosis. In-depth research on the prognosis of patients with anti-NMDAR encephalitis will contribute to a better understanding of this disease, leading to better treatments options and, ultimately, a better prognosis.

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Anti-NMDA Receptor Encephalitis: Clinical Features and Basic Mechanisms

Cited by 73 publications

References 107 publications

Pediatric Anti-NMDAR Encephalitis in Southern China: Analysis of 107 Cases

Pediatric Anti-NMDAR Encephalitis in Southern China: Analysis of 107 Cases

What’s Different about Teratoma-Associated LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series

Current Progress on Assessing the Prognosis for Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis

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