Pearls & Oy-sters: Relapse of anti-NMDA receptor encephalitis after prior first- and second-line immunotherapy

Abstract

Pearls cRelapse of anti-NMDA receptor (NMDAR) encephalitis should be considered in all patients with history of anti-NMDAR encephalitis presenting with new acute-onset encephalopathy or psychosis. c CSF antibody diagnostic testing is sensitive and specific for the initial diagnosis of anti-NMDAR encephalitis.c Although CSF antibody titers correlate more closely with disease severity than serum titers, the utility of comparison to baseline or remission titers in order to diagnose relapse is still under investigation. Oy-sters cLong-term clinical monitoring after anti-NMDAR antibody encephalitis is necessary for appropriate diagnosis and treatment of relapse, as the interpretation of elevated antibody titers without clinical change is of unclear significance. Although current confirmed cases suggest a median of 2 years between the initial episode and first relapse, increasing reports suggest that longer periods of monitoring may be needed.A 33-year-old right-handed woman with a history of anti-NMDA receptor (NMDAR) encephalitis presented with a 1-day history of vomiting and bizarre behavior in the context of recent cannabis and synthetic cannabinoid ingestion. She had been diagnosed 7 years earlier with anti-NMDAR encephalitis complicated by refractory epilepsy and treated with a 5-day course of IV methylprednisolone (IVMP), a 5-day course of IV immunoglobulin (IVIg), and 2 doses of rituximab. Her prior admission was characterized by a prolonged stay with slow clinical improvement ultimately resulting in complete resolution and no longer requiring antiepileptic medications. Anti-NMDAR immunoglobulin G (IgG) antibody was positive (titers not recorded) and CT chest/abdomen/pelvis, MRI pelvis, and transvaginal ultrasound were negative for malignancy. She was last seen at our institution 1.5 years prior to the current presentation without sequelae.On current presentation, the patient was initially hemodynamically stable with intact orientation and attention. Neurologic examination was significant only for diffuse hyperreflexia. Within an hour, she became acutely obtunded and developed orofacial dyskinesias, sensory anesthesia, tachycardia, and acral hyperhidrosis with no improvement over the next 3 days. Urine toxicology was positive for cannabinoids but basic laboratory studies (complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B 12 , folic acid, HIV, urinalysis) were unremarkable. On further workup, MRI brain with and without contrast was normal and showed neither T2 fluid-attenuated inversion recovery (FLAIR) changes nor enhancement. EEG showed diffuse slowing with no posterior dominant rhythm or epileptiform discharges. CSF showed 40 white blood cells (normal 0-5) with 90% lymphocytes and 10% monocytes, glucose 61 mg/dL (normal 50-80), protein 24.2 mg/dL (normal 15-45), and 0 red blood cells. CSF flow cytometry was negative for aberrant T-/B-cell populations, and cytology was negative for malignant cells. Routine CSF studies were negative for gram stain and culture, herpes simplex v...

The diffuse involvement of Anti-N-methyl-D-aspartate receptor encephalitis in brain: a case report

“…Anti-NMDAR encephalitis is the most common antibody-associated encephalitis and appears to be the leading cause of encephalitis in patients younger than 40 years old [3,13]. As reported, approximately 45% of anti-NMDAR encephalitis patients older than 18 years and 9% of girls younger than 14 years present with ovarian teratomas [12].…”

“…For anti-NMDAR encephalitis patients without remarkable improvement or without tumor, additional, second line immunotherapies, including mycophenolate mofetil, cyclophosphamide and rituximab, should be required [12]. Since the median length of time between symptoms onset and first relapse of anti-NMDAR encephalitis was 2 years, at least 2 years of long-term clinical monitoring is necessary [13].…”

A case of anti-N-methyl-d-aspartate receptor encephalitis

“…However, the clinical presentation of neuropsychiatric symptoms, the clinical symptom of orofacial dyskinesia, which is rather common and specific for anti-NMDAR encephalitis, negative HSV PCR in the CSF, as well as poor response to antiviral medications prompted us to consider the possibility of anti-NMDAR encephalitis. As both serum and CSF antibody is highly specific (96.3%–100%), 19 the positive serum anti-NMDAR antibody was sufficient for diagnostic confirmation. This (antibody diagnostics) is important when MRI and EEG findings are incongruent.…”

The diffuse involvement of anti-N-methyl-D-aspartate receptor encephalitis in brain: a case report

“…Anti-NMDAR encephalitis is the most common antibody-associated encephalitis and appears to be the leading cause of encephalitis in patients younger than 40 years old [3, 12]. As reported, approximately 45% of anti-NMDAR encephalitis patients over 18 years old and 9% of girls below 14 years old present with ovarian teratomas [11].…”

“…For anti-NMDAR encephalitis patients without remarkable improvement or without tumor, second line immunotherapies, including mycophenolate mofetil, cyclophosphamide and rituximab, should be required [11]. Since the median length of time between symptoms onset and first relapse of anti-NMDAR encephalitis was 2 years, a minimum of 2 years of long-term clinical monitoring is necessary [12].…”