Anti-NMDA receptor encephalitis pathophysiology: Difference between revisions
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{{Anti-NMDA receptor encephalitis}} | {{Anti-NMDA receptor encephalitis}} | ||
{{CMG}} AE{{DMakkar}} | {{CMG}}; AE {{DMakkar}} | ||
==Overview== | ==Overview== | ||
Anti-NMDA receptor encephalitis is an autoimmune disorder characterized by autoantibodies targeting GluN1. Tumors, primarily ovarian teratomas in women and testicular teratomas or lung carcinomas in men, are associated. Dysregulation of NMDARs leads to a range of neurological and psychiatric symptoms. | |||
==Pathophysiology== | ==Pathophysiology== | ||
Approximately sixty percent of individuals have tumors that contain nerve tissue. Majority of women have ovarian [[teratoma]], while men have tumors like (testicular [[teratoma]] and [[small-cell lung carcinoma)]]. | |||
Anti-NMDA receptor encephalitis is predominantly caused by autoantibodies directed against the GluN1 component of the receptor. | Anti-NMDA receptor encephalitis is predominantly caused by autoantibodies directed against the GluN1 component of the receptor. | ||
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*A model for the condition proposes that a decrease in NMDARs in inhibitory GABA neurons and glutamate synapses results in numerous effects, including dysregulation of glutamate release, elevated glutamate levels and excitatory circuits. | *A model for the condition proposes that a decrease in NMDARs in inhibitory GABA neurons and glutamate synapses results in numerous effects, including dysregulation of glutamate release, elevated glutamate levels and excitatory circuits. | ||
The clinical syndrome disinhibits the frontostriatal network, resulting in psychotic, catatonic, stiffness, dystonia, and mutistic symptoms. The brainstem central-pattern generator is disinhibited, resulting in complicated movement problems, and the brainstem respiratory network is also disinhibited, leading to respiratory dysfunction. | *The clinical syndrome disinhibits the frontostriatal network, resulting in psychotic, catatonic, stiffness, dystonia, and mutistic symptoms. | ||
*The brainstem central-pattern generator is disinhibited, resulting in complicated movement problems, and the brainstem respiratory network is also disinhibited, leading to respiratory dysfunction. | |||
NMDAR Dysregulation Proposed Symptoms | |||
Agonist effect on NMDARs Seizures | |||
Synaptic NMDAR hypofunction Amnesia, psychosis, hypoventilation | |||
Extrasynaptic NMDAR hyperfunction Catatonia, dyskinesias, seizures | |||
Neuronal network imbalance with impaired | |||
intraneuronal activity | |||
{| class="wikitable" | |||
|+ Synaptic effects and symptoms in anti-NMDARE: a proposed correlation | |||
|- | |||
! NMDAR Dysregulation | |||
! Proposed Symptoms | |||
|- | |||
| Agonist effect on NMDARs | |||
| Seizures | |||
|- | |||
| Synaptic NMDAR hypofunction | |||
| Amnesia, psychosis, hypoventilation | |||
|- | |||
| Extrasynaptic NMDAR hyperfunction | |||
| Catatonia, dyskinesias, seizures | |||
|- | |||
| Neuronal network imbalance with impaired intraneuronal activity | |||
| Seizures | |||
|} | |||
==References== | ==References== | ||
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[[Category:Rheumatology]] | [[Category:Rheumatology]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
<ref name="pmid24360484">{{cite journal| author=Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F | display-authors=etal| title=Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. | journal=Lancet Neurol | year= 2014 | volume= 13 | issue= 2 | pages= 167-77 | pmid=24360484 | doi=10.1016/S1474-4422(13)70282-5 | pmc=4006368 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24360484 }} </ref> | |||
{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
Latest revision as of 06:08, 13 May 2023
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; AE Dheeraj Makkar, M.D.[2]
Overview
Anti-NMDA receptor encephalitis is an autoimmune disorder characterized by autoantibodies targeting GluN1. Tumors, primarily ovarian teratomas in women and testicular teratomas or lung carcinomas in men, are associated. Dysregulation of NMDARs leads to a range of neurological and psychiatric symptoms.
Pathophysiology
Approximately sixty percent of individuals have tumors that contain nerve tissue. Majority of women have ovarian teratoma, while men have tumors like (testicular teratoma and small-cell lung carcinoma).
Anti-NMDA receptor encephalitis is predominantly caused by autoantibodies directed against the GluN1 component of the receptor.
In the acute phase of brain diseases, B cells, plasma cells, CD4 T cells, and, less frequently, CD8 T cells have been detected.
Crossing the blood-brain barrier enables systemically produced antibodies to crosslink NMDA receptors. This leads to their internalization and a severe disruption of synaptic plasticity and NMDA receptor network function.
- A model for the condition proposes that a decrease in NMDARs in inhibitory GABA neurons and glutamate synapses results in numerous effects, including dysregulation of glutamate release, elevated glutamate levels and excitatory circuits.
- The clinical syndrome disinhibits the frontostriatal network, resulting in psychotic, catatonic, stiffness, dystonia, and mutistic symptoms.
- The brainstem central-pattern generator is disinhibited, resulting in complicated movement problems, and the brainstem respiratory network is also disinhibited, leading to respiratory dysfunction.
NMDAR Dysregulation Proposed Symptoms Agonist effect on NMDARs Seizures Synaptic NMDAR hypofunction Amnesia, psychosis, hypoventilation Extrasynaptic NMDAR hyperfunction Catatonia, dyskinesias, seizures Neuronal network imbalance with impaired intraneuronal activity
| NMDAR Dysregulation | Proposed Symptoms |
|---|---|
| Agonist effect on NMDARs | Seizures |
| Synaptic NMDAR hypofunction | Amnesia, psychosis, hypoventilation |
| Extrasynaptic NMDAR hyperfunction | Catatonia, dyskinesias, seizures |
| Neuronal network imbalance with impaired intraneuronal activity
|
Seizures |
References
- ↑ Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F; et al. (2014). "Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study". Lancet Neurol. 13 (2): 167–77. doi:10.1016/S1474-4422(13)70282-5. PMC 4006368. PMID 24360484.