A patient with encephalitis associated with NMDA receptor antibodies. Nat Clin Prac 3:291-296

Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Nature Clinical Practice Neurology (Impact Factor: 7.64). 06/2007; 3(5):291-6. DOI: 10.1038/ncpneuro0493
Source: PubMed


A 34-year-old woman presented with headache, feverish sensation and anxiety, rapidly followed by homicidal ideation, aggressive agitation, seizures, hypoventilation, hyperthermia and prominent autonomic instability requiring intubation and sedation. She developed episodes of hypotension and bradycardia with periods of asystole lasting up to 15 seconds. Upon weaning off sedation, her eyes opened but she was unresponsive to stimuli. There was muscle rigidity, frequent facial grimacing, rhythmic abdominal contractions, kicking motions of the legs, and intermittent dystonic postures of the right arm.
Routine laboratory testing, toxicology screening, studies for autoimmune and infectious etiologies, brain MRI scan, lumbar puncture, electroencephalogram, whole-body CT scan, abdominal ultrasound, paraneoplastic and voltage-gated potassium channel antibody serologies, analysis of N-methyl-D-aspartate receptor antibodies.
Paraneoplastic encephalitis associated with immature teratoma of the ovary and N-methyl-D-aspartate receptor antibodies.
Intensive care, mechanical ventilation, antiepileptics, laparotomy and left salpingo-oophorectomy, corticosteroids, plasma exchange, intravenous immunoglobulin, cyclophosphamide, physical therapy, and chemotherapy.

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Available from: Erdem Tüzün, Jul 11, 2014
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    • "A recently reported case series attempted to differentiate male ANRE from female ANRE and suggested that male patients, similar to our case, present with early seizures, whereas behavioral changes are more common as an early manifestation in female patients [12]. Seizures are a common feature of ANRE [2] [13] [14] and occur in more than two-thirds of patients (76/100) in a recently published large series [1]. A few refractory cases of SE as a result of ANRE have been reported; however, their details were not specified. "
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    ABSTRACT: Anti-NMDA receptor encephalitis (ANRE) has been previously reported as a rare cause of nonconvulsive status epilepticus (NCSE). Vagus nerve stimulation (VNS) is generally considered as a palliative treatment for patients with drug-resistant partial-onset epilepsy. Here, we report a case of refractory NCSE that was terminated after vagus nerve stimulator implantation. To our knowledge, similar cases have not been reported previously.
    Epilepsy and Behavior Case Reports 12/2015; 3. DOI:10.1016/j.ebcr.2015.02.003
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    • "Another feature of anti-NMDAR encephalitis is that it predominantly affects women of reproductive age (Kamei et al. 2009), and is often accompanied by ovarian teratoma (Dalmau et al. 2007, 2008). Mature-and immature-appearing neurons in ovarian teratoma ectopically express NMDARs (Sansing et al. 2007; Seki et al. 2008; Tüzün et al. 2009); this is thought to contribute to the production of anti-NMDAR antibodies. Therefore, anti- NMDAR encephalitis has been considered to be a type of paraneoplastic encephalitis (Vitaliani et al. 2005; Dalmau et al. 2007). "
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    ABSTRACT: Autoimmune synaptic encephalitis is characterized by the presence of autoantibodies against synaptic constituent receptors and manifests as neurological and psychiatric disorders. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is such an autoimmune disorder that predominantly affects young women. It is associated with antibodies against the extracellular region of the NR1 subunit of postsynaptic NMDAR. Each NMDAR functions as a heterotetrameric complex that is composed of four subunits, including NR1 and NR2A, NR2B, or NR2C. Importantly, ovarian teratoma is a typical complication of anti-NMDAR encephalitis in female patients and may contain antigenic neural tissue; however, antigenic sites remain unknown in female patients without ovarian teratoma. The purpose of this study was to investigate the expression of NMDARs in the ovum. We detected NR1 and NR2B immunoreactivity in protein fractions extracted from the bovine ovary and ova by SDS-polyacrylamide gel electrophoresis and immunoblotting analysis. Immunoprecipitates digested with trypsin were analyzed by reverse phase liquid chromatography coupled to tandem mass spectrometry. We obtained the following five peptides: SPFGRFK and KNLQDR, which are consistent with partial sequences of human NR1, and GVEDALVSLK, QPTVAGAPK, and NEVMSSK, which correspond to those of NR2A, NR2B and NR2C, respectively. Immunocytochemical analysis revealed that the bovine ovum was stained with the immunoglobulin G purified from the serum of a patient with anti-NMDAR encephalitis. Taken together, we propose that the normal ovum expresses NMDARs that have strong affinity for the disease-specific IgG. The presence of NMDARs in ova may help explain why young females without ovarian teratomas are also affected by anti-NMDAR encephalitis.
    The Tohoku Journal of Experimental Medicine 03/2015; 235(3):223-31. DOI:10.1620/tjem.235.223 · 1.35 Impact Factor
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    • "Presences of antibodies against the GluN1 subunit of the NMDAR in the CSF and/or serum confirm the diagnosis of NMDAR encephalitis, which also should prompt a thorough search for an underlying tumor [2] [3] [4]. Age, gender and ethnicity may all play a role, as Asian and African American females older than 18 years of age have an increased likelihood of an underlying tumor, most commonly teratoma [2] [3] [5] [32]. Treatment is focused on tumor resection and first-line immunotherapy (corticosteroids, plasma exchange and intravenous immunoglobulin). "
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    ABSTRACT: Anti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007, has been increasingly identified as a significant cause of autoimmune and paraneoplastic encephalitis. Approximately 80% of the patients are females. The characteristic syndrome evolves in several stages, with approximately 70% of the patients presenting with a prodromal phase of fever, malaise, headache, upper respiratory tract symptoms, nausea, vomiting and diarrhoea. Next, typically within two weeks, patients develop psychiatric symptoms including insomnia, delusions, hyperreligiosity, paranoia, hallucinations, apathy and depression. Catatonic symptoms, seizures, abnormal movements, autonomic instability, memory deficits may also develop during the course of the disease. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis, which also should prompt a thorough search for an underlying tumor. Age, gender, and ethnicity may all play a role, as black females older than 18 years of age have an increased likelihood of an underlying tumor. Treatment is focused on tumor resection and first-line immunotherapy [corticosteroids, plasma exchange, and intravenous immunoglobulin]. In non-responders, second- line immunotherapy [rituximab or cyclophosphamide or combined] is required. More than 75% of the patients recover completely or have mild sequelae, while the remaining patients end up demonstrating persistent severe disability or death. There is a paucity of literature on the management of psychiatric symptoms in this population. Given the neuropsychiatric symptoms in the relatively early phase of the illness, approximately 77 % of the patients are first evaluated by a psychiatrist. Earlier recognition of this illness is of paramount importance as prompt diagnosis and treatment can potentially improve prognosis. We describe two patients diagnosed with NMDAR encephalitis presenting with two different psychiatric manifestations. The first patient presented with psychotic mania and catatonic symptoms, while the second suffered from depression with psychotic and catatonic features refractory to psychotropic medications. We review of the use of psychotropic medications and ECT to address insomnia, agitation, psychosis, mood dysregulation and catatonia in NMDAR encephalitis.
    General hospital psychiatry 03/2014; 36(4). DOI:10.1016/j.genhosppsych.2014.02.010 · 2.61 Impact Factor
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