An atypical case of progressive multifocal leukoencephalopathy in a patient with high grade B-cell lymphoma causing diagnostic delay

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare disease of the central nervous system caused by opportunistic infection with JC virus. It presents in patients who are immunocompromised, and diagnosis is made by correlating clinical findings and radiological changes with the detection of JC virus in cerebrospinal fluid. Rarely, a brain biopsy is needed. A 72 year old with high grade B-cell lymphoma developed right arm weakness and limb ataxia shortly after his diagnosis. CNS involvement was excluded with a normal CT head, MRI brain/spine, and CSF examination. A paraneoplastic cause was suspected, and he received 5 cycles of Rituximab-containing chemotherapy to a complete metabolic remission. His neurology evolved during treatment despite serial MRI and CSF examination remaining normal. CSF and serum were both negative for JC virus by PCR. Following completion of chemotherapy, he deteriorated acutely with seizures and personality changes. It was only at this point that a repeat MRI showed new multiple scattered ring enhancing lesions within both cerebral hemispheres. The patient underwent a brain biopsy confirming JC virus positive-PML by immunohistochemistry and passed away one month later. This case illustrates the diagnostic challenges associated with PML and had several atypical features which led to diagnostic delay, specifically the onset of symptoms before starting immunochemotherapy, and the lack of radiological change despite evolving neurology. The eventual MRI abnormalities were not altogether classical for PML which, coupled with the JC-negativity in CSF and serum, meant a brain biopsy was required to reach the diagnosis.