A previously healthy 19-year-old male presented with acute obtundation and right hemiparesis following a viral prodrome. MRI revealed a T2 hyperintensity in the left frontal subcortex extending into the brainstem. CSF was inflammatory (WBC 1,475, 94% PMN). Additional workup was notable for negative serum MOG and AQP-4 antibodies. Treatment with high-dose steroids and plasma exchange initially led to clinical and MRI stabilization but while on steroid taper, the patient experienced an acute decline with extensive brainstem involvement and hydrocephalus. A ventricular drain was placed, and he received a second round of high-dose steroids, plasma exchange as well as two doses of cyclophosphamide. Brain biopsy revealed evidence of AHL. Whole genome sequencing demonstrated biallelic CFI variants and complement testing was consistent with functional CFI-deficiency (low C3, absent Factor B, absent AH50). After cell counts recovered, another worsening occurred with evidence of longitudinally-extensive flaccid myelitis and inflammatory CSF (2,015 WBC). Anakinra therapy was initiated resulting in sustained remission of neuroinflammation over 5 months to date with gradual improvement in his clinical examination. 

CFI-deficiency can manifest with a severe relapsing neuroinflammatory syndrome with AHL and myelitis. Rapid genetic diagnosis in the neuro-ICU may be helpful to clarify diagnosis in such cases. IL-1R inhibition can help treat autoinflammation in this syndrome.