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Proton MR Spectroscopy of Progressive Multifocal Leukoencephalopathy−Immune Reconstitution Inflammatory Syndrome
==================================================================================================================

* V. Cuvinciuc
* G. Martin-Blondel
* B. Marchou
* F. Bonneville

We read with great interest the article by Bag et al1 entitled “JC Virus Infection of the Brain.” In this work, the authors dedicated a significant section to the inflammatory forms of progressive multifocal leukoencephalopathy (PML), referred to as PML-immune reconstitution inflammatory syndrome (IRIS). The authors underlined how this diagnosis may be challenging because there is no available biomarker of PML-IRIS and also because the suggestive MR imaging findings of PML-IRIS, namely the onset of contrast enhancement and/or mass effect of white matter T2 hyperintensities, are inconsistently present.1,2 Thus, proton MR (1H-MR) spectroscopy, a technique that studies the metabolism of the brain and lesions in vivo, could be of interest in demonstrating specific modifications in cases of PML-IRIS. However, as Bag et al1 noticed, while 1H-MR spectroscopy has already been reported in PML, the literature lacks spectroscopic descriptions of PML-IRIS. Herein, we wanted to briefly report our experience with serial 1H-MR spectroscopy in a patient with PML-IRIS.

A 48-year-old man was admitted with a right frontal cerebral toxoplasmic abscess revealing human immunodeficiency virus-1 (HIV-1) infection. After the abscess was evacuated emergently, MR imaging was performed and showed confluent T2 hyperintensity in the left corona radiata, with no gadolinium uptake, compatible with PML (Fig 1*A*). Short TE 1H-MR spectroscopy of the left corona radiata lesion showed a mild elevation of choline (Cho), a diminution of *N*-acetylaspartate (NAA), the presence of lactate (Lac)/lipids at 1.3 ppm, and the presence of myo-inositol (mIns) (Fig 1*B*). Combined antiretroviral treatment was started. Two months later, the patient developed subacute right hemiplegia, while the HIV load had decreased by >2 log10 copies/mL. MR imaging showed a marked increase of the left white matter T2 hyperintensity, with mass effect (Fig 1*C*) and contrast enhancement. Subsequent short and long TE proton spectra showed an additional increase of Cho and Lac/lipid peaks (Fig 1*D*), compared with the spectrum of PML acquired before combined antiretroviral treatment initiation and immune restoration. Stereotactic brain biopsy further confirmed PML-IRIS.

![Fig 1.](http://www.ajnr.org/http://ajnr-stage2.stage.highwire.org/content/ajnr/31/8/E69/F1.medium.gif)

[Fig 1.](http://www.ajnr.org/content/31/8/E69/F1)

Fig 1. 
*A*, Fluid-attenuated inversion recovery (FLAIR) axial image shows high signal intensity in the left corona radiata, compatible with PML. Note the right frontal postsurgical appearance after evacuation of a cerebral abscess. *B*, Short TE spectroscopy shows increased Cho, free lipids (and/or Lac), and diminished NAA. *C*, After 2 months of treatment, with adapted biologic response but paradoxic clinical worsening, axial FLAIR image reveals an enlargement of the left T2 hyperintensity with obvious mass effect on the ipsilateral ventricle. *D*, Short TE spectroscopy shows further increase in Cho, Lac, and free lipid peaks (long TE not shown). Glx indicates glutamine/glutamate; lip, lipid; mI, myo-inositol.

In conclusion and responding to Bag et al,1 we report a case of paradoxic PML-IRIS with serial MR spectroscopy features consistent with an increased inflammatory response. While the elevation of the mIns/creatine ratio has been shown to be associated with better survival rates in patients with PML,3 we propose that serial spectroscopy could be a diagnostic marker of PML-IRIS, deserving further study.

## References

1.  1. Bag AK, Cure JK, Chapman PR, et al. JC virus infection of the brain. AJNR Am J Neuroradiol 2010 Mar 18. [Epub ahead of print]
    
    

2.  2. Tan K, Roda R, Ostrow L, et al. PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology 2009;72:1458–64
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjEwOiI3Mi8xNy8xNDU4IjtzOjQ6ImF0b20iO3M6MTk6Ii9ham5yLzMxLzgvRTY5LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Katz-Brull R, Lenkinski RE, Du Pasquier RA, et al. Elevation of myoinositol is associated with disease containment in progressive multifocal leukoencephalopathy. Neurology 2004;63:897–900
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjg6IjYzLzUvODk3IjtzOjQ6ImF0b20iO3M6MTk6Ii9ham5yLzMxLzgvRTY5LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

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