Viral or Autoimmune? Acute Encephalitis in the Setting of Newly Diagnosed Primary Immunodeficiency

Encephalitis in immunocompromised individuals presents a unique diagnostic and treatment challenge due to the interplay between infection and immune dysregulation. A 48-year-old male with a history of recurrent sinusitis presented for seizure, agitation, rightward gaze, and fevers. He became obtunded and required intubation. Brain MRI showed three foci of acute-subacute infarcts in the left parietal and posterior temporal lobes. Chest X-ray revealed a right lower lobe infiltrate. Workup was positive for Mycoplasma pneumonia and Bordetella bronchiseptica. Cerebrospinal fluid (CSF) was positive for HSV-1 and undetectable IgG. Serum immunoglobulins were IgG <8, IgA <7, and IgM <5. B cell phenotyping revealed increased naive B cells and decreased memory cells and plasmablasts. Given that the radiological findings were not consistent with pure HSV encephalitis and an absence of blood in the CSF, there was concern for a parainfectious autoimmune encephalitis in the setting of newly diagnosed hypogammaglobulinemia. He received acyclovir, steroids, and high-dose intravenous immunoglobulins (IVIg) over 5 days. Repeat MRI showed worsening vasogenic edema. With concern for vasculitis, a brain biopsy was performed, which revealed a predominance of CD8+ T cells with no detectable B cells. HSV-1 was negative on biopsy; however, this was post-treatment. He improved in language function; however, he did not return to baseline and required further psychiatric hospitalization. Monthly IVIg was continued. This case is notable for CD8+ T cell predominance on brain biopsy with newly diagnosed hypogammaglobulinemia, suggesting possible T cell dysfunction leading to autoimmune encephalitis in the absence of immunoglobulins. Toll-like receptor and primary immunodeficiency genetic panel are pending. It highlights the importance of immunologic evaluation and a multidisciplinary approach to the diagnosis and treatment of patients with atypical encephalitis.