Progressive Multifocal Leukoencephalopathy in a Child with Nephrotic Syndrome

Dear Editor, The introduction of biological agents has significantly transformed the management of several pediatric diseases. Rituximab has emerged as an effective therapeutic option for children with steroid-dependent and calcineurin inhibitor (CNI)-resistant nephrotic syndrome (NS).[1] However, prolonged immunosuppression associated with such therapies predisposes patients to rare opportunistic infections. We report the case of a 7-year-old boy who presented with a gradual onset of walking difficulty over a year, which had progressively worsened. According to his parents, the symptoms were preceded by a febrile episode that was treated as meningitis at another facility, requiring hospitalization for a month. Following discharge, the child developed generalized weakness, frequent falls, gait imbalance, incoordination, tremors, and became non-ambulatory. The child had a history of NS that had been treated with steroids, CNIs, and rituximab, with the last dose administered 3 years earlier. He had remained in remission since then, and all immunosuppressive agents had been discontinued. On examination, the child demonstrated impaired cognitive functions, including memory and intelligence, were impaired. Spasticity was present in all four limbs, with brisk deep tendon reflexes and positive cerebellar signs. Magnetic resonance imaging of the brain revealed multifocal, asymmetric, periventricular, and subcortical lesions without significant mass effect [Figure 1], consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid analysis showed elevated protein levels, while the neuroviral panel was negative. Further evaluation showed persistently low serum immunoglobulin levels and cluster of differentiation 19 counts of <1%, consistent with secondary agammaglobulinemia following rituximab therapy. The child was started on cotrimoxazole prophylaxis, and the parents were counseled regarding the prognosis.Figure 1: Magnetic resonance imaging of the patient with progressive multifocal leukoencephalopathy. (A–D) Multifocal asymmetric subcortical T2-weighted fluid-attenuated inversion recovery hyperintensities in both frontoparietal subcortical white matter and cerebellar white matter without mass effect (white arrows)Post-rituximab-associated PML has been previously documented in patients with systemic lupus erythematosus, malignancies, and in the recipients of chemotherapy or stem cell transplantation.[2] However, reports of PML in the context of NS are exceedingly rare. In a longitudinal study by Delbue et al.,[3] polyomavirus replication in NS was not found to be associated with rituximab therapy. Similarly, a retrospective cohort study by McAtee et al.[4] did not report any case of PML during a 12-month follow-up post-rituximab, although persistent hypogammaglobulinemia was reported. To the best of our knowledge, this represents the first reported case of PML in a child with NS. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.