scholarly journals Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures

2021 ◽  
Vol 15 ◽  
Author(s):  
Olga Taraschenko ◽  
Howard S. Fox ◽  
Ember Eldridge ◽  
Wenyi Wang ◽  
Samuel W. Dowd ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nmda Receptor ◽  
Clinical Manifestations ◽  
Continuous Administration ◽  
Nmda Receptor Encephalitis ◽  
Cortical Screw ◽  
Abnormal Movements ◽  
Continuous Eeg ◽  
Ccl2 Mrna ◽  
Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified NMDA receptor antibodies from encephalitis patients to mice precipitated seizures, thereby confirming that antibodies are directly pathogenic for seizures. Although different repertoires of anti-NMDA receptor antibodies could contribute to the distinct clinical manifestations in encephalitis patients, the role of specific antibodies in the expression of seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived monoclonal antibodies with distinct epitopes within the N-terminal domain (NTD) of the NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11 antibodies for 2 weeks precipitated seizures, as measured with continuous EEG using cortical screw electrodes. The seizure burden was comparable in all three antibody-treated groups. The seizures were accompanied by increased hippocampal C-C chemokine ligand 2 (CCL2) mRNA expression 3 days after antibody infusion had stopped. Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal antibodies targeting different epitopes within the NMDA receptor may result in a similar seizure phenotype.

scholarly journals Anti-N-Methyl-D-Aspartate Encephalitis as Paraneoplastic Manifestation of Germ-Cells Tumours: A Cases Report and Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Claudia Geraldine Rita ◽  
Israel Nieto Gañan ◽  
Adriano Jimenez Escrig ◽  
Ángela Carrasco Sayalero
Keyword(s):  
Nmda Receptor ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Cell Tumour ◽  
Clinical Manifestations ◽  
Autoimmune Encephalitis ◽  
Cell Tumour ◽  
Ovarian Teratoma ◽  
Surgical Removal ◽  
Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by the interaction between an antibody and its target, located on glutamate receptor type N-methyl-D-aspartate (NMDA) of neuronal surface. There is a wide spectrum of clinical features starting by a viral-like prodrome, followed by symptoms such as psychosis, aggressive behaviour, memory loss, seizures, movement disorders, and autonomic instability. Up to 50% of the affected young female patients have germ-cells tumours as ovarian teratoma, making it essential to establish an early diagnosis through detection of specific antibodies in serum and cerebrospinal fluid (CSF). This retrospective observational study was performed in patients whom positive anti-NMDA receptor antibodies have been tested, associated with clinical manifestations that suggest autoimmune encephalitis and a germ-cell tumour confirmed by pathology. Six patients have tested positive for anti-NMDA receptor antibodies associated with a germ-cell tumour and clinical manifestations of autoimmune encephalitis. Management includes aggressive immunosuppression and surgical removal.

scholarly journals Severe tooth loss secondary to orofacial dyskinesias in anti-NMDA receptor encephalitis

2019 ◽  
Vol 12 (3) ◽  
pp. e228380
Author(s):  
Daniel Garbin Di Luca ◽  
Jason H Margolesky
Keyword(s):  
Emergency Department ◽  
Nmda Receptor ◽  
Tooth Loss ◽  
Altered Mental Status ◽  
Psychiatric History ◽  
Aggressive Treatment ◽  
Orofacial Dyskinesia ◽  
Speech Output ◽  
Nmda Receptor Encephalitis ◽  
Receptor Antibodies

A 24-year-old woman with no significant medical or psychiatric history was brought to the emergency department due to altered mental status and bizarre behaviour. Physical examination was remarkable for decreased speech output and orofacial dyskinesia. Upon further evaluation, electroencephalogram showed extreme delta brush waves and cerebrospinal fluid was positive for anti-NMDA receptor antibodies. Despite aggressive treatment with steroids and immunosuppressive therapy, her dyskinesia was severe enough to cause tooth loss, tongue and lip laceration.

scholarly journals Unilateral predominance of abnormal movements: A characteristic feature of the pediatric anti-NMDA receptor encephalitis?

2017 ◽  
Vol 7 ◽  
pp. 42-44 ◽  
Author(s):  
Vanessa Benjumea-Cuartas ◽  
Monika Eisermann ◽  
Hina Simonnet ◽  
Marie Hully ◽  
Rima Nabbout ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Characteristic Feature ◽  
Nmda Receptor Encephalitis ◽  
Abnormal Movements

Anti-NMDA-receptor encephalitis: aethology of psychiatric symptoms in young women

2011 ◽  
Vol 26 (S2) ◽  
pp. 876-876
Author(s):  
E. Marin Diaz-Guardamino ◽  
L. Larrañaga Rementeria ◽  
I. Hervella Garces ◽  
T. Aldasoro Carcedo ◽  
J. Fernandez Bilbao ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Young Women ◽  
Language Impairment ◽  
Psychiatric Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Initial Assessment ◽  
Nmda Receptor Encephalitis ◽  
Women And Girls ◽  
Receptor Antibodies ◽  
Rule Out

IntroductionAnti-NMDA-receptor encephalitis is subacute disorder that has been recently described in young women and girls who often present neuropsychiatric symptoms as first clinical features; thus, it is common that they receive an initial assessment, diagnose or even treatment by a specialist in Psychiatry.ObjectivesPresenting a case of Anti-NMDA-receptor encephalitis that was observed at our hospital and the steps taken from its initial assessment by Psychiatry to the final diagnose and treatment by Neurology, our objective is to describe this disorder in order to make it known to the specialists in Psychiatry.MethodsThe case is that of a 14 year old girl who presents altered behavior, bizarre delusions and auditory hallucinations with subacute onset. In psychiatric assessment it is noted that the patient presents fever, slight and language impairment: Medical and Neurological assessment are requested. The steps followed to rule out other disorders are presented. SPECT and the detection of specific anti-NMDA-receptor antibodies in serum were necessary for an accurate diagnose.ResultsThe detection of specific antibodies is necessary for the diagnose of Anti-NMDA-receptor encephalitis. NMDA receptors are ligand-gated cation channels with crucial roles in synaptic transmission and plasticity. Their alteration could be a pathogenic mechanism in disorders such as epilepsy, dementia and schizophrenia.ConclusionsAnti-NMDA-receptor encephalitis is a recently described clinical entity that should be taken in consideration to rule out other causes of subacute onset psychiatric symptoms in young women and girls. Its well-defined set of clinical characteristics should become familiar to the specialists in Psychiatry.

Management And Psychiatric Manifestations Of Anti-NMDA Receptor Encephalitis, A Case Report

2016 ◽  
Vol 33 (S1) ◽  
pp. S525-S526
Author(s):  
R. Gallego ◽  
A. Flores
Keyword(s):  
Case Report ◽  
Nmda Receptor ◽  
Psychiatric Symptoms ◽  
Multidisciplinary Treatment ◽  
Autoimmune Disorder ◽  
Clonic Seizure ◽  
Nmda Receptor Encephalitis ◽  
Abnormal Movements ◽  
Nmdar Encephalitis ◽  
Psychiatric Manifestations

IntroductionAnti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007 by Dalmau et al, is an autoimmune disorder with a complex presentation that includes psychiatric symptoms, memory deficits, and autonomic instability. The exact incidence is unknown but age, gender, and ethnicity may all play a role. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis.Case reportWe report the case of a previously healthy, 19-year-old woman, 6 weeks pregnant. She had a generalized tonic-clonic seizure followed by psychiatric symptoms, including insomnia, emotional lability, delusions, and disorganized behavior. During the course of the disease, she demonstrated speech impairments and catatonic features associated with abnormal movements.She was provided lorazepam 1 mg twice a day to treat her catatonic symptoms, her insomnia and her speech improved. Olanzapine was introduced, reaching a dose of 20 mg/day for managing psychosis and agitation.DiscussionNMDA-R encephalitis is a novel disorder with prominent psychiatric manifestations that is widely underdiagnosed. Neuroleptics may be helpful for managing psychosis and agitation, but may exacerbate movement abnormalities. Benzodiazepines are helpful for agitation, insomnia and catatonia associated with this condition.ConclusionEarlier recognition of this illness is crucial as prompt diagnosis and multidisciplinary treatment, can potentially improve prognosis. There is an increasing need for psychiatrists to become aware of the disorder and consider it in their differential diagnosis, specially in patients with new onset psychosis, history of encephalitis or subtle neurological symptoms. Careful selection of psychopharmacological interventions may reduce suffering.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Clinical approach to the diagnosis and successful management of anti-NMDA receptor encephalitis when antibody testing is not possible

2019 ◽  
Vol 12 (10) ◽  
pp. e229593
Author(s):  
Anil Frank Ramlackhansingh ◽  
Alexi Christopher King ◽  
Shamera Maharaj ◽  
David Joseph King
Keyword(s):  
Black Women ◽  
Nmda Receptor ◽  
Mature Teratoma ◽  
Memory Deficits ◽  
Ovarian Teratoma ◽  
Clinical Approach ◽  
Antibody Testing ◽  
Nmda Receptor Encephalitis ◽  
Abnormal Movements ◽  
Children And Young Adults

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a multistage illness that progresses from psychosis, memory deficits, seizures and language disintegration to a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. While the disorder predominantly affects children and young adults, and occurs with or without tumour association, the presence of a tumour (usually an ovarian teratoma) is dependent on the age, sex and ethnicity.Teratomas present more frequently in women older than 18 years, and are more predominant in black women than Caucasians. Here we present the case of a patient with probable anti-NMDA receptor encephalitis. She was subsequently found to have a mature teratoma of the ovary (dermoid cyst). Despite immune-modulated therapy, surgery was eventually performed to remove the cyst. This was met with a good clinical recovery.

Bortezomib for treatment of anti–NMDA receptor encephalitis in a pediatric patient refractory to conventional therapy

2021 ◽  
Vol 78 (5) ◽  
pp. 395-400 ◽  
Author(s):  
Marroyln L Simmons ◽  
Kimberly A Perez
Keyword(s):  
Nmda Receptor ◽  
Clinical Improvement ◽  
Pediatric Patient ◽  
Mental Status ◽  
Clinical Status ◽  
Inpatient Rehabilitation ◽  
High Dose ◽  
Nmda Receptor Encephalitis ◽  
High Dose Methylprednisolone ◽  
Receptor Antibodies

Abstract Purpose The case of a pediatric patient with treatment refractory anti–N-methyl-d-aspartate (NMDA) receptor encephalitis treated with the plasma cell–depleting therapy bortezomib is reported. Summary A 5-year-old female presented to the hospital with a 1-week history of altered mental status, agitation, and possible seizure-like activity. She was admitted to the hospital for suspected meningitis or meningoencephalitis and an extensive workup was completed, including sending blood and cerebrospinal fluid (CSF) for testing for NMDA receptor antibodies. While test results were pending, the patient was treated initially with intravenous immunoglobulin (IVIG) for 4 days followed by high-dose methylprednisolone for 5 days. The patient’s serum and CSF studies were positive for NMDA receptor antibodies, confirming the diagnosis of anti–NMDA receptor encephalitis. She was then treated with plasmapheresis therapy every other day for 5 treatments, without any clinical improvement. The patient then received rituximab once weekly for 6 weeks. Three weeks after completion of rituximab therapy, the patient was started on her first cycle of bortezomib therapy. She received a total of 6 cycles, with improvement in her clinical status beginning with the third cycle. Upon completion of 6 cycles, the patient’s mental status and level of functioning had greatly improved. She was discharged to an inpatient rehabilitation facility and ultimately able to return home to her family. Conclusion A 5-year-old female with anti–NMDA receptor encephalitis was successfully treated with bortezomib after having shown no clinical improvement during treatment with IVIG, high-dose methylprednisolone, plasmapheresis, and rituximab.

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