Published ahead of print on June 10, 2010
doi: 10.3174/ajnr.A2160

American Journal of Neuroradiology 31:E69-E70, September 2010
© 2010 American Society of Neuroradiology

V. Cuvinciuc^a
aNeuroradiology Department
University Hospital
Toulouse, France
and
Neuroradiology Department
University Hospital
Grenoble, France

G. Martin-Blondel^b
bInfectious and Tropical Diseases Department
University Hospital
Toulouse, France
and
INSERM UB563
Toulouse, France

B. Marchou^c
cInfectious and Tropical Diseases Department
University Hospital
Toulouse, France

F. Bonneville^d
dNeuroradiology Department
University Hospital
Toulouse, France

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, protonMR (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 1A). 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 1B). 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 1C) and contrast enhancement. Subsequent short and long TE proton spectra showed an additional increase of Cho and Lac/lipid peaks (Fig 1D), compared with the spectrum of PML acquired before combined antiretroviral treatment initiation and immune restoration. Stereotactic brain biopsy further confirmed PML-IRIS.

View larger version (79K): [in this window] [in a new window] 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. 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. 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]
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]

Reply

Published ahead of print on June 10, 2010
doi: 10.3174/ajnr.A2176

American Journal of Neuroradiology 31:E71, September 2010
© 2010 American Society of Neuroradiology

A.K. Bag^a, J.K. Cure^a, P.R. Chapman^a, G.H. Roberson^a and R. Shah^a
aDepartment of Radiology
Division of Neuroradiology
University of Alabama at Birmingham Medical Center
Birmingham, Alabama

We greatly appreciate the authors’ interest in our work and thank them for their contribution to the discussion. Not having encountered a case of immune reconstitution inflammatory syndrome (IRIS) with progressive multifocal leukoencephalopathy (PML) in our institution, we hypothesized possible MR spectroscopic findings in our article, which were confirmed by the authors’communication. The authors’ example showed elevated choline and mildly elevated myo-inositol peaks as we postulated in our article in addition to a lactate peak. These spectroscopic abnormalities presumably reflect an intense inflammatory response associated with the PML-IRIS. The baseline MR spectroscopy before development of PML-IRIS helped to elucidate the metabolic changes attributable to PML-IRIS.