Seizures as first symptom of anti-NMDA receptor encephalitis are more common in men

There has been a rapid increase in the characterization of encephalitis associated with antibodies to cell surface or synaptic proteins,¹ starting with the report of 4 patients with prominent psychiatric symptoms who rapidly progressed into hypoventilation and coma.² The disorder was subsequently identified as anti-NMDA receptor (NMDAR) encephalitis, now the best characterized and most frequently recognized autoimmune encephalitis,³ demonstrating that “newly identified” does not always mean “infrequent” or “rare.” In addition to frequency, 2 reasons for the sharp increase in the identification of patients with this syndrome are the characteristic clinical features that facilitate its recognition on clinical grounds and the specificity of the diagnostic test that when properly used leaves no margin for error.⁴ The latter is straightforward: examine the patient's CSF with HEK cells expressing GluN1 or GluN1/2 subunits of the NMDAR (the cell-based assay [CBA] used commercially or in research laboratories). If only serum is used, there is a risk (∼15%) of false-negative or false-positive results⁵; this risk decreases if the serum is examined with an additional confirmatory test, such as immunohistochemistry with rat brain tissue. If these criteria are not used, the specificity of the test decreases and the presumed “spectrum” of symptoms enlarges.