Abstract Details

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is caused by reactivation of the JC virus, usually in the setting of profound cellular immunosuppression. We present 3 cases without any known immunosuppressive state who presented with PML and after extensive workup were found to have immune system abnormalities that were previously undiagnosed and asymptomatic.

Case 1: A 51-year-old man presented with cognitive dysfunction including dyslexia, agraphia, aphasia, and right-sided weakness. MRI brain revealed T2/FLAIR hyperintensities in the left parieto-occipital lobe. Further immunologic workup revealed positive PM/Scl-100 antibody, positive ANA titer at 1:80, and low CD4 count of 41/mm³.

Case 2: A 67-year-old woman with idiopathic immune complex-mediated membranoproliferative glomerulonephritis presented with rapid cognitive decline and left-sided weakness. MRI brain revealed multifocal T2/FLAIR hyperintensities and a large right frontal lesion with partial enhancement. Extensive immunologic workup revealed positive ANA at 1:640 but no other abnormalities.

Case 3: A 72-year-old woman presented with left-sided weakness. MRI brain showed right frontal T2/FLAIR hyperintensities. Immunologic workup revealed positive ANA at >1:2560, positive SSA antibody, low complement C3 at 73, C4 at <2, elevated IgG at 1,698 mg/dL, low white blood cell count of 2,600/mm³ with lymphopenia at 830/mm³ and low CD4+ T cells at 299/mm³. Flow cytometry showed clonal expansion of CD5-/CD10- B lymphocytes indicative of a lymphoproliferative malignancy.

In all 3 cases, HIV was negative and PML was confirmed with brain biopsy.

PML may occur without apparent profound immunocompromise and therefore should be included in the differential when investigating compatible white matter abnormalities in patients without known immune dysfunction. It may be the initial presenting illness of an underlying immune system abnormality that was not previously clinically evident. A thorough immunologic workup is warranted when PML is diagnosed in an otherwise immunocompetent individual.