MR-Perfusion Patterns of Progressive Multifocal Leukoencephalopathy Lesions Affect the Risk of Developing IRIS
Abstract & Commentary
By Joseph Safdieh, MD
Assistant Professor of Neurology, Weill Cornell Medical College
Dr. Safdieh reports no financial relationships relevant to this field of study.
Synopsis: Hyperperfusion of progressive leukoencephalopathy lesions (PML) on MRI predicts progression of PML and reduced risk of immune reconstitution inflammatory syndrome.
Source: Khoury MN, et al. Hyperperfusion in progressive multifocal leukoencephalopathy is associated with disease progression and absence of immune reconstitution inflammatory syndrome. Brain 2013;136:3441-3450.
Progressive multifocal leukoencephalopathy (pml) is a central nervous system opportunistic infection caused by the JC virus. Originally described in patients with hematologic malignancies, it became quite common in the height of the AIDS era and over the past few years has been noted in the setting of immunomodulatory therapy for multiple sclerosis (MS) and a variety of other autoimmune disorders. The prognosis of patients with PML has traditionally been quite poor, but with the advent of highly active antiretroviral therapy (HAART), it has improved. However, reconstitution of the immune system, either with HAART in HIV patients or after withdrawal of the offending immunomodulatory therapy in patients with MS, can lead to immune reconstitution inflammatory syndrome (IRIS). PML-IRIS can cause worsening of neurological symptoms and imaging findings and can lead to permanent neurologic dysfunction if not identified and treated rapidly.
In this study, the authors studied the predictive value of the presence of hyperperfusion in PML lesions on the risk of progression and IRIS. MR-perfusion using arterial spin labeling does not require the administration of IV contrast and was used in this study to determine perfusion in PML lesions. The authors had initially hypothesized that hyperperfusion in PML lesions would be associated with increased immune activation and affect risk of IRIS. The study was designed as an observational study. Patients were divided retrospectively into survivors or progressors depending if they lived more than or less than 1 year from the onset of neurological symptoms. A total of 22 patients were enrolled. Eleven were survivors and 11 were progressors. The only statistically significant demographic difference between the groups was age, with median age 19 years older in the progressors than the survivors. Although HIV patients accounted for 64% of the survivors and 27% of the progressors, this was not a statistically significant difference. Initial Karnofsky score and modified Rankin scale score tended to be better in the patients who were ultimately survivors.
Hyperperfusion in PML lesions on MRI was found to be associated with a higher risk of progression and a lower risk of IRIS. In fact, only one PML survivor demonstrated hyperperfusion. The authors calculated a 9.1 relative risk of PML progression with hyperperfusion as measured by MRI. The presence of hyperperfusion in PML lesions was found to have sensitivity of 81.8% and specificity of 90.9% to predict progression. Additionally, the results suggested that hyperperfusion was also associated with reduced risk of developing IRIS. The mean perfusion was much lower in patients who developed IRIS compared to those who didn’t. The predictive value was quite good, with 90% of patients with hyperperfusion not developing IRIS. Additionally, hyperperfusion was not associated with contrast enhancement on MRI.
This study concludes that MR perfusion can risk-stratify patients with PML, with hyperperfusion associated with a higher risk of progression and a lower risk of IRIS. If validated, this would be a very useful predictive tool in clinical practice as it is noninvasive, does not require administration of IV contrast, and can be done at the same time patients obtain other standard MRI sequences. It is interesting that hyperperfusion is not associated with IRIS, as one might predict. Instead, the authors suppose that hyperperfusion may be directly related to viral activity. How can we apply these findings to neurologic practice? In patients with PML, we might order MR perfusion images and in patients who have hyperperfusion perhaps worry less that they will develop IRIS, but worry more about their overall prognosis.