To present a case elucidating sequential overlap between La Crosse encephalitis and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Prior infection is a known trigger for NMDAR encephalitis, with prior HSV meningoencephalitis being the most well studied. La Crosse virus is the most common neuroinvasive arbovirus in the U.S., with symptoms that closely overlap with those of autoimmune encephalitis (AE). We present a novel case of a patient developing NMDAR encephalitis triggered by La Crosse encephalitis.

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A 7-year-old previously healthy girl presented with one week of fever and headaches. MRI demonstrated leptomeningeal enhancement. Cerebrospinal fluid (CSF) analysis showed pleocytosis and negative CSF arboviral antibodies, so she was diagnosed with presumed viral encephalitis. Of note, serum arbovirus titers (higher sensitivity than CSF) were not tested. Symptoms initially improved, but over the next two weeks she worsened with abnormal behavior and seizures. CSF pleocytosis had resolved but eight oligoclonal bands were present; MRI showed decreased but persistent enhancement.  Steroids were started due to concern for AE, but discontinued when serum arbovirus testing returned positive, consistent with La Crosse encephalitis. However, in the weeks following discharge, she experienced a further psychiatric and cognitive decline. Subsequently, her serum and CSF resulted positive for NMDA-IgG, confirming the diagnosis of NMDAR encephalitis. She was treated with intravenous immunoglobulin and rituximab with good response in her symptoms.

AE can often follow viral illness, but its association with La Crosse encephalitis is not well described. This is a novel presentation of NMDAR encephalitis triggered by La Crosse encephalitis with overlapping symptoms and delayed recognition.  AE workup should be considered in patients with positive arbovirus serology with continued clinical progression of symptoms.  While poor outcomes have been described in NMDAR encephalitis following HSV encephalitis, our patient ultimately experienced a good outcome.  MRI, electroencephalogram, and sequential neuropsychiatric testing data will be presented.