Progressive Multifocal Leukoencephalopathy Following Treatment with Rituximab in an HIV-Negative Patient with Non-Hodgkin Lymphoma. A Case Report and Literature Review

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare rapidly progressive demyelinating disease of the central nervous system caused by reactivation of latent John Cunningham (JC) polyomavirus (JCV) infection. We describe an unusual case of PML in a 54-year-old patient with follicular non-Hodgkin lymphoma who received rituximab plus cyclophosphamide, hydroxydaunorubicin, oncovicin and prednisolone (R-CHOP) therapy. She started to notice gradual progressive neurological symptoms about two months after completion of rituximab treatment and was therefore admitted to hospital. On admission, brain CT and MRI showed widespread lesions consistent with a demyelinating process involving the subcortical and deep white matter of the cerebral and cerebellar hemispheres. CT and MRI findings were suggestive of PML, and JC virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid and serum. The patient was treated supportively but reported a progressive worsening of the clinical and radiological findings. Our report emphasizes the role of CT and MRI findings in the diagnosis of PML and suggests that PML should be considered in patients with progressive neurological disorders involving the entire nervous system and mainly the white matter, especially in the presence of previous immunomodulatory treatment or immunosuppression.

Keywords: JC virus; follicular non-Hodgkin lymphoma; progressive multifocal leukoencephalopathy; rituximab.

Figure 1

Initial MRI images obtained some days after the onset of neurological symptoms (January 2014). Axial FLAIR did not show any significant alterations.

Figure 2

CT obtained on admission (February 2014) showed multiple hypodense lesions in the white matter of the cerebral and cerebellar hemispheres.

Figure 3

MRI obtained on admission (February 2014). Axial FLAIR showed multiple hyperintense lesions of the subcortical and deep white matter, symmetrically involving the cerebral hemispheres and cerebellum. The lesions were round or ovoid without significant mass effect, did not conform to cerebrovascular territories and were consistent with PML.

Figure 4

MRI obtained on admission (February 2014). On T1-weighted sequences obtained after administration of gadolinium, the lesions did not show enhancement.

Figure 5

MRI obtained on admission (February 2014). The proton MR spectrum demonstrated a mild elevation of the choline (Cho) peak, with an increased Cho/Cr ratio, and a slightly decreased N-acetyl aspartate peak, with a mildly reduced NAA/Cr ratio. There were also a mild elevation of mI (myo-inositol) and two abnormal peaks at 0.9 ppm and, greater, at 1.3 ppm, due to the presence of lactate and lipids, with an increased lac/Cr and lipids/Cr ratio.

Figure 6

Follow-MRI obtained two months after hospital admission (April 2014). Axial FLAIR at almost the same levels as Figure 3 showed an increase in the number and width of the lesions.