We describe two cases of SLIPPERS syndrome, emphasizing its clinical and diagnostic heterogeneity, as well as the challenges encountered in its recognition and management.

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids syndrome (SLIPPERS syndrome) is a rare neuro-inflammatory disorder predominantly affecting the brain's supratentorial regions.¹

The case series draws on a detailed review of clinical data for two patients who were monitored at Ochsner Health, ensuring a comprehensive and insightful analysis of their medical journeys for this study.

Case 1 details a 25-year-old man with a history of asthma and childhood seizures, presenting with a generalized tonic-clonic seizure. MRI revealed a heterogeneously enhancing lesion in the left frontal lobe. Despite normal cerebrospinal fluid (CSF) analysis, a biopsy indicated peri-vascular T-cell predominant inflammation. Steroid treatment was initiated, yielding a positive response. Case 2 involves a 19-year-old woman with no significant past medical history who experienced drug-induced seizures and developed progressive neurological symptoms. Her MRI demonstrated T2 FLAIR hyperintensities with enhancement, indicating an inflammatory process. Biopsy showed reactive T-cell perivascular inflammation. The patient's condition evolved, requiring increased steroid treatment and adjunctive rituximab therapy. Both cases involved initial seizure control with levetiracetam and demonstrated clinical improvement with steroids, supporting an inflammatory etiology. However, the cases differed in their progression and complexity of diagnosis.

In summary, these cases highlight the diverse manifestations of SLIPPERS syndrome, ranging from isolated lesions with autoimmune features to more elusive, progressive patterns requiring extensive investigation and treatment adjustments. This series emphasizes the need for clinical vigilance to facilitate early detection and treatment of SLIPPERS syndrome, a condition with diverse symptoms and considerable diagnostic hurdles. These cases add to the evidence aiding comprehension of SLIPPERS syndrome's clinical and pathological characteristics.