To describe a case of supratentorial lymphocytic inflammation with parenchymal perivascular enhancement responsive to steroids (SLIPPERS) presenting as isolated subacute cognitive changes with radiographic bilateral thalamic-predominant involvement. 

SLIPPERS is a rare, recently characterized inflammatory syndrome with radiologic and pathologic overlap with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Fewer than twenty cases of SLIPPERS have been reported, and its full clinical and imaging spectrum remains incompletely defined.

A previously independent man in his late 60s presented with 2 months of progressive short-term memory loss, disorientation, and executive dysfunction, eventually requiring hospitalization. Neurologic examination showed isolated cognitive deficits without other focal neurological deficits. MRI demonstrated asymmetric bilateral thalamic T2/FLAIR hyperintensities extending to the superior colliculi/tectal plate and periaqueductal gray with patchy enhancement, as well as susceptibility changes consistent with microhemorrhages. Cerebrospinal fluid studies showed mildly elevated protein with otherwise unrevealing profile, including unremarkable glucose, cell count, meningitis/encephalitis panel, gram stain/culture, or flow cytometry. Broad serum infectious, inflammatory, and metabolic workup was unrevealing. Given clinical concern for SLIPPERS, he was treated with pulse-dose methylprednisolone followed by a prolonged oral prednisone taper, with rapid clinical improvement during hospitalization and continued recovery thereafter. At outpatient follow-up, family reported return to near-baseline cognition, with repeat MRI demonstrating interval normalization. He was subsequently transitioned to mycophenolate mofetil as a steroid-sparing agent.

SLIPPERS is a rare steroid-responsive inflammatory disorder with few reported cases in the literature. Prior descriptions include seizures, headache, hemiparesis, and cognitive dysfunction with punctate or curvilinear perivascular enhancement. This case expands the radiographic spectrum by demonstrating bilateral thalamic-predominant deep gray involvement with tectal/periaqueductal extension, as well as microhemorrhagic changes. Clinically, it highlights isolated cognitive decline without additional focal deficits as a presenting feature. Overall, this case contributes to defining the broader clinical and radiographic spectrum of SLIPPERS.