Pembrolizumab-responsive cerebellar PML in untreated sarcoidosis: a case report

Progressive multifocal leukoencephalopathy (PML) is a rare but devastating demyelinating disease usually seen in immunocompromised patients. We describe a 52-year-old man with pulmonary sarcoidosis, who presented with progressive ataxia, dysarthria, and unsteadiness of gait. He was not on immunosuppressive therapy at the onset of balance problems. Initial imaging showed increased signal in the cerebellar peduncles suggestive of cerebellar variant of multiple system atrophy (MSA-C). Cerebellar biopsy revealed PML. The patient’s condition deteriorated until pembrolizumab, a PD-1 checkpoint inhibitor, was commenced. He subsequently showed slow but sustained clinical improvement, supported by radiological (reduced enhancement) and spectroscopic evidence (increased N-Acetyl Aspartate to Creatine ratio), and he remains stable four years later. This case highlights the diagnostic challenge of PML in the absence of ongoing immunosuppression, and illustrates the potential role of pembrolizumab as a disease-modifying therapy. Early recognition and consideration of immunotherapy may be critical to improving outcomes in this otherwise often fatal condition.