Anti-NMDAR encephalitis with concomitant varicella zoster virus detection and nonteratomatous malignancy

Discussion

This case report demonstrates a rare presentation of anti-NMDAR encephalitis with concomitant VZV detection in the setting of a nonteratomatous gynecologic tumor.^1,2 In a seminal case series published in 2008, about 60% of patients with anti-NMDAR encephalitis had a tumor, most often an ovarian teratoma.³ Anti-NMDAR encephalitis has also been linked with tumors of endocervical and endometrial origin.⁴ These tumors express NMDA receptor 1 (NR1), as well as synaptophysin, neuron-specific enolase, CD56, and chromogranin. Resection of tumors that express NRs can shorten recovery time.⁵ Our patient's tumor expressed synaptophysin, but NR1 testing was not performed. Thus, it is unknown whether her cervicouterine tumor demonstrates a true association with NMDAR immunoreactivity.

Neurotropic viruses, most frequently HSV, have been linked to anti-NMDAR encephalitis.⁶ One proposed mechanism for this association is that these viruses may lyse neurons, releasing antigens that sensitize IgG antibodies to the NR and triggering autoimmune encephalitis.^1,2 Another hypothesis is that CNS inflammation from anti-NMDAR encephalitis may cause shedding of latent viral DNA or a viral reactivation leading to secondary encephalitis.⁷

To date, VZV has been documented twice in the setting of anti-NMDAR encephalitis.^1,2 One patient presented with cranial nerve palsies and improved significantly after treatment with IV acyclovir and immunoadsorption. The other patient had a teratoma and presented with confusion and behavioral changes after a viral-like illness. She was refractory to treatment with teratoma resection, acyclovir, IVIG, and plasma exchange.

Our patient completed the full first-line therapy for both anti-NMDAR and VZV encephalitis. Although her improvement in symptoms correlated temporally with antiviral therapy, the effects of the IVMP and IVIG treatment cannot be discounted because the response to immunotherapy often lags behind its completion. Because she was treated for both disease processes, it is unclear whether VZV triggered our patient's autoimmune condition or was present in the CSF as a result of latent viral shedding. Her presenting symptoms were more consistent with anti-NMDAR encephalitis than VZV encephalitis. Nevertheless, we recommend antiviral treatment in cases of anti-NMDAR encephalitis with concomitant VZV detection because the immunosuppressive regimen for anti-NMDAR encephalitis may worsen an underlying VZV infection.

Previous literature suggests that anti-NMDAR encephalitis should be considered in any person aged 50 years or younger who presents with acute psychotic changes of less than 4 weeks' duration, especially in the setting of a viral prodrome or abnormal movements.⁵ Current standard of care for patients with suspected anti-NMDAR encephalitis is to treat with acyclovir until HSV PCR testing is complete. Our case is part of a growing body of evidence that suggests providers should continue antiviral treatment until VZV PCR testing has resulted negative as well. Additional research could investigate the optimum treatment course and prognosis when anti-NMDAR encephalitis presents with concomitant viral detection.