A 35-year-old Hispanic female, with no significant past medical history, first presented after a witnessed seizure but rapidly developed confusion, flat affect, agitation, and suicidal ideation necessitating inpatient psychiatric hold and high dose antipsychotics. She further deteriorated becoming unresponsive while displaying prominent orofacial dyskinesias, muscle rigidity, and autonomic instability that resulted in periodic hyperthermia, tachy-brady syndrome, hypotension, and hypoventilation. She required sedation, mechanical ventilation, and vasopressor support in the intensive care unit. An extensive workup was entailed that included neurological, infectious, toxic, autoimmune, and paraneoplastic studies. Lumbar puncture with cerebrospinal (CSF) studies revealed high oligoclonal bands and IgG synthesis index but brain MRI was normal. Electroencephalogram (EEG) showed generalized slowing and delta-range activity suggestive of severe encephalopathy. Infectious, toxic, and paraneoplastic studies were negative. Autoimmune workup revealed positive N-methyl D-aspartate receptor (NMDAR) antibodies in the CSF confirming the diagnosis of anti-NDMAR encephalitis. Patient was empirically treated with IV steroids and IVIG followed by Rituximab with substantial improvement in her neurological status and near-complete clinical recovery.
Anti-NMDAR encephalitis results from IgG antibodies against the NRI subunit of NMDA receptors, which are localized in the central nervous system and play an important role in synaptic transmission and memory function. The syndrome is characterized by a multistage illness that rapidly progresses from psychosis, memory deficits, seizures, and language dysfunction into a state of unresponsiveness with catatonic features. About 80% of patients are women between the ages of 18 to 35 and 40% have an underlying tumor. Since its discovery in 2007, hundreds of cases of anti-NMDAR encephalitis has been described in the medical literature; although, it remains a diagnostic mystery in most institutions. Most clinicians fail to recognize or are unfamiliar with the characteristic symptoms and unnecessarily subject their patients to psychiatric treatments. Additionally, delay in diagnosis risks significant morbidity and mortality. Hence, clinicians must know the features of anti-NMDAR encephalitis and have a high index of suspicion to diagnose and treat it. Diagnosis is based on clinical presentation and positive anti-NMDAR antibodies in the serum or CSF. Standard treatment is with 5 days of IV steroids plus IVIG and removal of tumor if one exists. Rituximab and/or cyclophosphamide may be added to the treatment regimen if the former fails. About 75% of patients recover or have mild sequelae with early diagnosis and treatment. Others remain severely disabled or die.
Anti-NMDAR encephalitis is an increasingly recognized and potentially treatable autoimmune disorder that often presents with neuropsychiatric symptoms. Children and young adults are predominately affected and most cases have a paraneoplastic association, commonly ovarian teratomas. Diagnosis is confirmed with positive anti-NMDAR antibodies in the serum or CSF. The mainstays of treatment are early diagnosis, tumor work-up and removal if found, and initiation of immunosuppressive therapy.
To cite this abstract:Ram A, Amiri H. An Emerging Diagnosis: A Mysterious Encephalitis. Abstract published at Hospital Medicine 2016, March 6-9, San Diego, Calif. Abstract 751. Journal of Hospital Medicine. 2016; 11 (suppl 1). https://www.shmabstracts.com/abstract/an-emerging-diagnosis-a-mysterious-encephalitis/. Accessed March 31, 2020.