|Year : 2018 | Volume
| Issue : 1 | Page : 68-71
Suspected anti-N-methyl-D-aspartate receptor encephalitis in the setting of a 26-year-old female with an ovarian carcinoma
Lauren V Burton, Christopher David Wilbert, Michael I Silberman
Emergency Medicine Residency, University of Tennessee Health Science Center, Murfreesboro, Tennessee, United States of America
|Date of Submission||26-Oct-2017|
|Date of Acceptance||27-Nov-2017|
|Date of Web Publication||23-Apr-2018|
Dr. Christopher David Wilbert
University of Tennessee Health Science Center, Murfreesboro, Tennessee
United States of America
Source of Support: None, Conflict of Interest: None
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune encephalitis associated with ovarian tumors, rarely seen in emergency departments (EDs). There are proposed diagnostic methods and recommended treatment guidelines for anti-NMDAR, however, as this is a rare form of encephalitis, diagnostic, and treatment recommendations continue to be explored. We describe the case of a 26-year-old female patient who presented to our ED with altered mental status, exhibiting orofacial dyskinesias and choreathetoid movements. The patient was subsequently found to have an ovarian tumor and diagnosed with presumed anti-NMDAR encephalitis.
The following core competencies are addressed in this article: Medical knowledge, Patient care.
Keywords: Anti-N-methyl-D-aspartate receptor, anti-N-methyl-D-aspartate receptor encephalitis, autoimmune encephalitis, autoimmune encephalitis syndrome, emergency department, emergency medicine, encephalitis, ovarian tumors, paraneoplastic syndrome
|How to cite this article:|
Burton LV, Wilbert CD, Silberman MI. Suspected anti-N-methyl-D-aspartate receptor encephalitis in the setting of a 26-year-old female with an ovarian carcinoma. Int J Acad Med 2018;4:68-71
|How to cite this URL:|
Burton LV, Wilbert CD, Silberman MI. Suspected anti-N-methyl-D-aspartate receptor encephalitis in the setting of a 26-year-old female with an ovarian carcinoma. Int J Acad Med [serial online] 2018 [cited 2019 Jul 23];4:68-71. Available from: http://www.ijam-web.org/text.asp?2018/4/1/68/230858
| Introduction|| |
Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an autoimmune encephalitis syndrome most common in children and young adults. It presents with neurological and psychiatric changes, with just over half of all patients found to have underlying tumors, most often ovarian teratomas. First described in 2005 and first identified in 2007 anti-NMDAR encephalitis has recently become recognized as the most common cause of autoimmune encephalitis. The disorder traditional is characterized by having a viral prodrome, memory deficits, changes in speech, seizures, movement disorders (choreoathetoid movements, muscle rigidity, orofacial dyskinesias, etc.,), central hypoventilation, and psychiatric symptoms (hallucinations, delusions, agitation, catatonia, etc.).,,,,
Despite the increased frequency of recognition, many patients are initially missed in the emergency department (ED) and are incorrectly diagnosed with psychiatric conditions. The purpose of this article is to increase awareness of what many clinicians describe as a singular event.
| Case Report|| |
A 26-year-old female patient with a history of attention deficit disorder (ADD) presented to the ED after exhibiting bizarre behavior. History was primarily provided by the patient's significant other secondary to clinical status. The patient's significant other reported that the patient had been flapping her hands, sticking out her tongue, and looking around in unusual fashions. The patient had a similar episode about 4 weeks prior, however, the patient's symptoms resolved while in the parking lot of the ED, and therefore, the patient decided not to seek treatment. The patient herself had no complaints and the review of systems was only positive for weight gain. Questioning regarding whether the patient was known to be pregnant was repeatedly denied by the boyfriend.
On physical examination, the patient was noted to be afebrile, normotensive, tachypneic, and tachycardic. She was flapping her arms in the room, sticking out her tongue, and displaying bizarre ocular movements. The patient was disoriented, her neck was supple, no extremity clonus was observed, no focal neurologic deficits were found and the patient had normal symmetric reflexes. The patient would not attempt to track with her eyes but was moving all four extremities spontaneously. The patient was noted to have a large distended abdomen without jaundice or fluid wave.
Eventually, the patient's mother arrived and provided a past medical history that included ovarian torsion due to a large right-sided benign ovarian mass which resulted in a salpingo-oophorectomy. The patient and family had noticed increasing abdominal swelling over the past 6 months. The patient's clinical condition continued to deteriorate while in the ED and the patient was intubated for airway protection.
Computed tomography (CT) of the head and chest X-ray showed no acute abnormalities. Laboratory studies were relatively unremarkable. Urine drug screen was positive for amphetamines believed to be related to her ADD medication. The patient had a negative urine pregnancy test. CT abdomen and pelvis without IV or oral contrast demonstrated a massive complex cystic and solid appearing mass that appeared to arise from the left ovary. Evaluation with ultrasound showed the same.
The patient was admitted to the Intensive Care Unit, gynecological oncology consult recommended exploration and surgical removal of the tumor. On the 2nd day of arrival, the patient had a 40 cm mass with surrounding smooth capsule surgically removed and was decompressed of 8.5 L of fluid. Pathology reports revealed a borderline ovarian mucinous tumor with intraepithelial carcinoma. Subsequently, the patient received 5 days of plasmapheresis secondary to concern for possible autoimmune encephalitis. Eight days after presentation, the patient had significant improvement with return to baseline mental status and was ultimately discharged home.
| Discussion|| |
Epidemiology of anti-NMDAR encephalitis includes a median age in the second decade of life with 95% of those affected <45 years of age. It has been reported to have a predilection in Asian and Pacific Islanders. Diagnosis is suspected in young females, presenting with symptoms first thought to be manifestations of either an acute psychiatric process or toxidrome. Encephalitis with dyskinesias or abnormal movements was found to be anti-NMDAR encephalitis as frequently as 50% of the time in one case series.
In patients between the ages of the 12 and 45 years, the most common underlying tumor is the ovarian teratoma (94%). Only 23% of adults >45 years of age with anti-NMDAR encephalitis are found to have underlying tumors and these are most often carcinomas.
Diagnosis of anti-NMDAR encephalitis is confirmed by antibodies in cerebrospinal fluid (CSF) or serum to the NR1, also known as the GluN1, subunit of the NMDAR., However, the risk of false negatives and positives exist when the antibodies are tested in only serum as compared to CSF, as prior studies have confirmed these antibodies in patients without anti-NMDAR encephalitis. CSF analysis will show lymphocytic pleocytosis or oligoclonal bands, however some cases have found CSF to be initially normal. Normal CSF was observed in our case; unfortunately, this was not obtained until 2 days after initial presentation. In 2016, Graus et al. proposed diagnostic criteria for anti-NMDAR encephalitis, as shown in [Table 1]. The patient did meet three groups of symptoms. Similarly, she had an associated ovarian carcinoma, although not a teratoma, therefore, posing the question of whether the diagnostic criteria could expand to include not only teratomas but also carcinomas.,
|Table 1: Diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis|
Click here to view
Magnetic resonance imaging (MRI) has been shown to be normal in up to 50% of those with clinically proven anti-NMDAR encephalitis. The remaining 50% of MRIs have demonstrated a hyperintensity of T2 or FLAIR images in multiple areas of the brain including cortical (cerebral and cerebellum) and subcortical regions (hippocampus, basal ganglia, and brainstem). Electroencephalograms (EEGs) are often abnormal frequently demonstrating slow disorganized activity.
Treatment of anti-NMDAR encephalitis is achieved through immunosuppression and tumor resection. Titulaer et al.'s large cohort study demonstrated substantial neurological improvement in 81% of patients at 24 months follow-up in patients who received both lines of therapy. Available studies suggest that patients with early tumor removal and immunotherapy had superior outcomes when compared to patients without tumor treatment.,,
Current treatment guidelines recommend intravenous immune globulin therapy (0.4 g/kg daily for 5 days) and methylprednisolone (1.0 g daily for 5 days). Plasma exchange can also be used as an alternative but is less effective in an unstable or uncooperative patient. Patients who do not respond to initial therapy in 10 days are recommended to receive a second-line therapy consisting of rituximab or cyclophosphamide. Relapses can occur and have been documented up to several years after initial presentation with a rate as high as 24%.
| Conclusion|| |
As emergency physicians, it is important to consider a broad differential diagnosis in patients presenting with altered mental status. In younger patients with orofacial dyskinesias, choreoathetoid movements, and altered mental status it is important to consider the diagnosis of anti-NMDAR encephalitis along with more conventional causes. Rapid identification and initiation of treatment including immunotherapy and tumor resection is critical to improve the prognosis of these patients.
Declaration of patient consent
The authors certify that they have obtained appropriate patient consent documentation, wherein the patient(s) has/ have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patient(s) understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosenfeld MR, Dalmau J. Anti-NMDA-receptor encephalitis and other synaptic autoimmune disorders. Curr Treat Options Neurol 2011;13:324-32.
Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al.
Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study. Lancet Neurol 2013;12:157-65.
Ferdinand P, Mitchell L. Anti-NMDA receptor encephalitis. J Clin Cell Immunol S 2012;10:2.
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al.
Aclinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391-404.
Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10:63-74.
Gable MS, Gavali S, Radner A, Tilley DH, Lee B, Dyner L, et al.
Anti-NMDA receptor encephalitis: Report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 2009;28:1421-9.
Titulaer MJ, McCracken L, Gabilondo I, Iizuka T, Kawachi I, Bataller L, et al.
Late-onset anti-NMDA receptor encephalitis. Neurology 2013;81:1058-63.
Dougherty ML. Anti-NMDA receptor encephalitis. Pract Neurol 2014;4:47-9.
Gabilondo I, Saiz A, Galán L, González V, Jadraque R, Sabater L, et al.
Analysis of relapses in anti-NMDAR encephalitis. Neurology 2011;77:996-9.