Progressive Multifocal Leukoencephalopathy Associated With Idiopathic CD8+ Lymphocytopenia

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by the polyoma John Cunningham (JC) virus. This virus is rarely pathogenic in immunocompetent individuals, being associated with profound cellular immunosuppression. We present a case of a 72-year-old woman with schizoaffective disorder who presented to the emergency department with dysarthria and right hemiataxia. The initial computer tomography was normal and the diagnosis of ischemic stroke was first assumed. However, during hospitalization there was a progressive worsening of symptoms with cerebellar ataxia, and the magnetic resonance revealed a lesion in the right middle cerebellar peduncle hypointense in T1 and hyperintense on T2/fluid attenuated inversion recovery (FLAIR) sequence, suggestive of PML. Although the first cerebrospinal fluid analysis was negative, the second one was positive for the JC virus. Furthermore, due to radiological and clinical progression, mirtazapine was started and the patient underwent a course of intravenous immunoglobulin, with no response. In parallel, causes of immunosuppression were investigated, which led to the diagnosis of idiopathic CD8+ lymphocytopenia. Due to rapid progression of symptoms and radiological worsening of lesions, pembrolizumab was administered. After the first administration of pembrolizumab there was a transitory clinical stabilization. However, shortly after the second administration of pembrolizumab, the patient developed stridor with bilateral vocal cord paralysis and subsequent symptom progression, which led to the death of the patient three months after the appearance of initial symptoms. In conclusion, we report a case of a PML in a patient with idiopathic CD8+ lymphocytopenia, enhancing the need for a high suspicion index for this entity as well as for occult and less frequent forms of immunosuppression. Although there have been various case reports of favourable outcomes with pembrolizumab for PML, more research is needed, particularly to identify patient factors that might be associated with better responses to this therapy.