To describe a rare case of CLIPPERS with initial infratentorial findings that later evolved into supratentorial disease consistent with SLIPPERS during poor treatment response.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a CNS inflammatory disease characterized on MRI by punctate and curvilinear gadolinium ‘peppering’ predominantly involving the brainstem and cerebellum. Patients typically present with subacute gait ataxia, diplopia, dizziness, dysarthria, and nystagmus. Supratentorial lesions may occur; predominant involvement is termed supratentorial lymphocytic inflammation with parenchymal perivascular enhancement responsive to steroids (SLIPPERS).

A 74-year-old male with chronic cervicalgia and OSA developed tinnitus and diplopia in 2021. Exam showed left gaze palsy and normal brain MRI. Patient was diagnosed with MRI-negative stroke, improved for three months, then developed ataxia, vertigo, bilateral hypoacusis, and falls requiring readmission. CSF showed elevated protein without pleocytosis and negative infectious, autoimmune, cytologic studies. MRI showed T2 hyperintensities in the brainstem, cerebellar hemispheres, thalami, subcortical white matter. Brain biopsy demonstrated perivascular lymphohistiocytic inflammation without vasculitis, granulomas, or neoplasm, consistent with CLIPPERS. Patient improved with IV steroids, prednisone taper, and methotrexate. After a 3-year stable period, patient developed dizziness, tinnitus, imbalance, cognitive impairment, and phosphenes. MRI showed new enhancing pontine, brainstem, and cerebellar lesions with right posterior corpus callosum infarcts. Vasculitis evaluation and GFAP antibodies were negative. Patient was treated with prednisone and switched to mycophenolate with partial improvement; however, symptoms worsened during tapering and repeat MRI showed progressive supra and infratentorial enhancing lesions involving bilateral basal ganglia, corpus callosum, parieto-occipital, and sensorimotor cortices, consistent with SLIPPERS. He improved after IV steroids and rituximab.  

CLIPPERS is a rare relapsing-remitting CNS disorder with unclear etiopathogenesis, classically involving infratentorial structures. Increasing reports describe a supratentorial variant termed SLIPPERS. This case supports a broader spectrum, suggesting inflammatory progression beyond the pons and cerebellum during uncontrolled disease.