JC virus infection of the brain

Abstract

Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE, JCVGCN, and JCM. Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency. IRIS may develop secondary to restoration of immunity in HIV-positive patients with PML receiving antiretroviral therapy. This is of profound clinical significance and needs to be diagnosed promptly. Imaging plays a crucial role in the diagnosis of the disease, monitoring of treatment response, identifying disease progression, and predicting prognosis. In this article, current understanding of the epidemiology, pathogenesis, clinical presentations, and all aspects of imaging of JCV infection of the brain have been comprehensively reviewed.

Fig 1.

Typical supratentorial right frontal cPML in an HIV-positive patient. A, On DWI, the lesion shows typical restricted diffusion along the advancing edge posteriorly (arrows) and facilitated diffusion centrally. B, On the ADC map, ADC value is low at the posterior advancing edge (arrow) and high at the center of the lesion. C, The lesion typically involves the subcortical U-fiber and is hypointense (relative to gray matter) on the T1-weighted sequence. Note the absence of mass effect from this moderate-sized lesion. D, There is no enhancement of the lesion on the postcontrast T1-weighted sequence. E, On the FLAIR sequence, there is hyperintensity in most parts of the lesion. Note the inversion of the FLAIR high signal anteriorly (arrow) due to intralesional cystic change. F, On the T2-weighted sequence, the entire lesion is hyperintense. Note the adjacent anterior cortex is relatively spared (arrow). G, On perfusion imaging, cerebral blood volume of the lesion is lower (arrow) than that of the contralateral white matter.

Fig 2.

Typical infratentorial cPML in another HIV-positive patient classically involving the middle cerebellar peduncle (left). A and B, This lesion also has diffusion restriction at the anterolateral advancing edge (high DWI signal intensity and low ADC value, arrows) and diffusion facilitation at the center as evidenced by the DWI (A) and the ADC map (B). C and D, The lesion shows typical hypointensity on the T1-weighted sequence (C) and hyperintensity on FLAIR (D). Note, there are no mass effect. There is no enhancement in the postcontrast T1-weighted sequence (E).

Fig 3.

There is an incomplete rim of T1 hyperintensity (arrows) at the advancing edges of the supratentorial (A) and infratentorial (B) cPML lesions.

Fig 4.

Progression of cPML. A and B, These FLAIR images, 4 months apart, from an HIV-positive patient with cPML demonstrate typical progression of the supratentorial white matter FLAIR hyperintensity.

Fig 5.

A, Intralesional microcyst on T2-weighted sequence on the left parietal cPML lesion in an HIV-positive patient, zoomed up in the inset. The arrow points to a microcyst. B, There are 2 intralesional microcysts (arrows) in this right fronto-parietal cPML lesion in another HIV-positive patient.

Fig 6.

Typical disease course of cPML in an HIV-positive patient receiving HAART. Top panel, a set of images at presentation with focal diffusion restriction (A and B) and very subtle but typical hypointensity on T1 (C) and hyperintensity on FLAIR (D). This initial study was confused with acute subcortical infarction. Middle panel, a set of images 1 month after the initial presentation. No HAART was administered before this scanning. Now the lesion has enlarged in size with typical diffusion restriction (arrows) at the medial and posterior advancing edges (E and F). Now the T1 hypointensity is more obvious (G). The adjacent cortex is not involved (arrows). Typically the lesion is hyperintense on FLAIR (H). Bottom panel, a set of images 19 months after initial presentation. The patient received HAART for 18 months. Now there is no diffusion restriction (I). On the T1-weighted sequence (J), there is profound T1 hypointensity associated with new/progressive atrophy. There is FLAIR hyperintensity in the adjacent areas. However, the main lesion is not hyperintense on FLAIR (K). On T2 (L), the lesion itself is very hyperintense compared with the adjacent white matter, suggesting cystic encephalomalacia. Note that the adjacent cortical architecture is preserved.

Fig 7.

Sequel of cPML. A and B, The 2 T2-weighted sequences, 16 months apart, from an HIV-positive patient demonstrate prominent brain atrophy with dilation of the ventricles and prominence of the sulci. Even at this advanced stage, there is minimal cortical involvement.