CLIPPERS and lymphoma: a unified syndrome

ABSTRACT

Background and aims: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a defined inflammatory central nervous system disorder characterized by established lesions, predominantly on the cerebellum and pons, with punctate gadolinium enhancement on the MRI and responsiveness to glucocorticosteroid-based immunosuppression. Its pathogenesis is unknown. Methods: A 54-year-old man, with history of obesity and alcoholism, was admitted to our emergency ward due to fever, disorientation, and behavior disorder for 3 days. The neurological examination manifested left eye ptosis and unceasing left gaze torsional nystagmus. He tested positive for SARS-CoV2. A lumbar puncture revealed 41 leucocytes/ mm3, with negative antibody determinations. MRI depicted hyperintense lesions on cerebellum, brain stem, left temporal lobe and right parieto-occipital cortex, with punctate gadolinium enhancement. There was a radiological and clinical response to glucocorticosteroid treatment. He was diagnosed of possible CLIPPERS. Results: Several months following the discharge, after the patient voluntarily abandoned the treatment, the symptoms reappeared. A new MRI showed extensive lesions suitable with primary lymphoma. A biopsy confirmed the diagnosis. In situ hybridization detected Epstein-Barr virus (EBV). Conclusion: Reports describing the development of lymphoma on patients previously diagnosed with CLIPPERS, and the fact that both conditions share anatomopathological findings such as infiltrating CD4+ lymphocytes, support the theory of a syndrome with various prestages encompassing both entities. Furthermore, a nexus between B-cell lymphoma and EBV has already been established, but recent studies dwell on the possibility of this same infection being one of the main triggers of CLIPPERS and its progression into lymphoma.