Treatment of Progressive Multifocal Leukoencephalopathy Associated with Natalizumab

Abstract

We describe the clinical and therapeutic course of a 52-year-old patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML) developed after 12 months of therapy with natalizumab. The patient was hospitalized 2 months after the onset of neurologic and psychiatric symptoms and was treated with plasma exchange and immunoadsorption to eliminate natalizumab. After a brief improvement, he became critically ill with an apparent episode of immune reconstitution inflammatory syndrome. Steroid-pulse therapy led to stabilization of the patient's condition and clinically significant recovery. This case illustrates that prompt diagnosis and treatment may improve the outcome in patients with severe PML associated with natalizumab therapy.

Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient

“…31 The same pattern has also been observed after discontinuation of natalizumab treatment in patients with multiple sclerosis developing PML. [32][33] In our patient, the recovery of specific immunity, and, in particular, of JCVspecific cytotoxic T-cell populations, contributed to viral control without inducing an immune reconstitution-related syndrome. This may be the result of JCV-specific CTL infusion, as the presence of mature effector cells activated in vitro may have enhanced endogenous virus-specific immunity without the activation of unspecific effector cells, likely responsible for reconstitution-related inflammatory reaction.…”

Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

“…3) in 56-86% of patients, with associated edema and mass effect. [69][70][71][72] Nonetheless, non-enhancement of a PML lesion with clinical deterioration does not preclude the diagnosis. To date, there is no biomarker that confirms IRIS.…”

CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function

“…One major risk attributable to a4 integrin blockade has been the occurrence of cases with progressive multifocal leukoencephalopathy observed after natalizumab therapy. 10,11 Recently, it has been reported that the number of circulating CD34 þ HSC markedly increases during natalizumab treatment in MS patients. 12,13 These reports have raised great interest, because they have opened the prospect of examining CD49d blockade as a new mobilization strategy.…”