Severe Progressive Multifocal Leukoencephalopathy (PML) and Spontaneous Immune Reconstitution Inflammatory Syndrome (IRIS) in an Immunocompetent Patient

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with JC-virus (JCV), a papova-virus, affecting mostly oligodendrocytes and the white matter of the central nervous system. Progressive Multifocal Leukoencephalopathy (PML) almost exclusively occurs in immunocompromised patients based on different underlying conditions of severe cellular immunodeficiency such as HIV/AIDS, secondary to neoplastic and autoimmune diseases, or during immunosuppressive therapy. Case presentation: We present the case of an otherwise healthy and immunocompetent patient without immunosuppressive therapy who was admitted with hemianopsia to the right side, sensory aphasia and changes of behavior. Magnet resonance imaging (MRI) and laboratory testing confirmed the diagnosis of PML, although functional tests did not show any evidence for cellular immunodeficiency. Extensive immunological tests did not reveal an apparent immunodeficiency. During symptomatic therapy the patient developed seizures which were assumed to be caused by a spontaneous immune reconstitution inflammatory syndrome (IRIS) demonstrated by MRI. We added a high dose of intravenous corticosteroids to the antiepileptic treatment and seizures ended shortly thereafter. However, the impairments of vision, behavior and language persisted. Conclusions: Our case report highlights that an apparently immunocompetent patient can develop PML and IRIS spontaneously. Therefore, MRI should be applied immediately whenever a rapid progression of PML symptoms occurs as treatment of IRIS with corticosteroids can result in a marked clinical improvement.

Keywords: JC-virus; corticosteroid; immunocompetence; progressive multifocal leukoencephalopathy (PML); spontaneous immune reconstitution inflammatory syndrome (IRIS).

Figure 1

MR examination showing typical findings of PML with white matter FLAIR- (A) and T2 weighted- (B) hyperintensities without mass effect. T2-signal elevations (B) are in part spot-like and resemble the milky-way-appearance typical for PML. The area affected by the JC-virus infection does have a typical rim with reduced ADC values (C, white arrow) indicating the inflammatory border zone with acute demyelination combined with swelling of astrocytes and oligodendrocytes.

Figure 2

Tomograms of ¹⁸F-FDG uptake (A) as well as the result of SPM analysis (B, using an uncorrected p < 0.001 for statistical inferences) revealed distinct bilateral hypo-metabolism pronounced on the left side in parietotemporal and occipital areas. Note, unlike in tomograms the left side appears left in the SPM images.

Figure 3

MR examination showing the progress of the PML-related FLAIR-hyperintensities (A). The new multifocal and strong contrast enhancement (B) indicates the PML-IRIS. The zone of active inflammation and demyelination is again indicated also by the low ADC-rim surrounding the area affected by the JC-virus (C, white arrow).