Clinico-pathological correlation in unilateral cortical encephalitis treated with tocilizumab after first-line treatment failure.

OBJECTIVES

To characterize clinico-pathologic findings and therapeutic response in a rare case of unilateral cortical encephalitis successfully treated with tocilizumab after first-line treatment failure, highlighting potential immune mechanisms.

METHODS

Case report.

RESULTS

A 49-year-old man developed fever, seizure, and hemicortical deficits. MRI showed right cortical T2-hyperintensity, gyral enhancement, corresponding to 18F-FDG-PET hypermetabolism, compatible with unilateral cortical encephalitis. Extensive metabolic, infectious, and malignancy workup was unrevealing. Neural autoantibodies were negative. 6-months of progressive cognitive decline, visual, speech, and gait disturbance and an infectious event (appendicitis) preceded acute unihemispheric encephalitic syndrome. Brain biopsy demonstrated increased cortical perineuronal microglial activation, retraction of astrocytic processes from microvessels suggestive of blood-brain barrier disruption, and mainly perivascular CD4+T-cell infiltrates, alongside excess circulating interleukin-18 collectively implicating innate and adaptive immune mechanisms. Initial treatment with pulse steroids and intravenous immunoglobulin failed to yield improvement. Tocilizumab as second-line treatment concomitant to weekly pulse steroids led to significant recovery in cognition, gaze deviation, speech, and gait and resolution of imaging abnormalities.

DISCUSSION: Tocilizumab-an IL-6 receptor blocker-was selected given the pleiotropic role of IL-6 in proinflammatory CD4+T-cell differentiation (Th17/Treg imbalance) and innate immune-driven CNS inflammation. This case illustrates the utility of clinico-pathological correlation and cytokine profiling in guiding immunotherapy selection in antibody-negative autoimmune encephalitis.