Objective:

To report a case of progressive multifocal leukoencephalopathy (PML) in the setting of idiopathic CD4 lymphopenia in an otherwise immunocompetent-appearing patient and highlight the challenges and importance of early recognition. 

Background:

PML is a rare demyelinating disease of the central nervous system caused by JC virus reactivation in the setting of an immunocompromised state. PML is most commonly seen in patients with HIV infection, immunosuppressive therapy, or hematologic malignancy. Rarely, PML can present in patients with idiopathic lymphocytopenia without other signs of impaired immunity, leading to diagnostic delays and poor outcomes. 

Design/Methods:

NA

Results:

79-year-old man presented with right hemi-body incoordination and dysarthria. His MRI brain showed a right cerebellopontine T2-hyperintense lesion with diffusion restriction but no enhancement, initially concerning for infarct. He subsequently developed worsening symptoms with scanning speech, right sided dysmetria, decreased right facial sensation, and reduced right eye abduction, and a two-week interval MRI showed progression of the cerebellopontine lesion with new punctate enhancement. HIV testing was negative, but he was found to have profound CD4 lymphopenia (84 cells/μL). He tested positive for serum JC virus DNA and antibody and CSF JC virus DNA. Brain biopsy demonstrated multifocal demyelination, astrocyte atypia, and oligodendrocytes with SV40+ intranuclear inclusions, consistent with PML. The patient had no prior exposure to immunosuppressive therapy or history of frequent infections. Extensive evaluation for malignancy, viral infection, and primary immunodeficiency was unremarkable. He was successfully enrolled in an experimental treatment trial and his initial course shows promising viral clearance. 

Conclusions:

Although PML is rare in patients without HIV or exposure to immunosuppressive therapy, it is important to consider idiopathic lymphopenias as a risk factor in otherwise immunocompetent-presenting individuals. Early recognition and diagnosis of PML allow for timely initiation of immunotherapeutic intervention and supportive management.