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Differences of Apparent Diffusion Coefficient Values in Patients with Creutzfeldt-Jakob Disease According to the Codon 129 Genotype
===================================================================================================================================

* D. Galanaud
* D. Dormont
* S. Haïk
* J. Chiras
* J.P. Brandel
* J.P. Ranjeva

We read with great interest the article by Tschampa et al1 analyzing the patterns of lesions, mostly on cortical areas, in patients with Creutzfeldt-Jakob disease (CJD). Although this study confirmed the high sensitivity of diffusion imaging, the authors did not find any differences between the 3 subtypes (MM, MV, VV) of the disease associated with the methionine/valine polymorphism at codon 129 of the prion protein gene. In this retrospective study, only diffusion-weighted images (DWIs) were reviewed, and apparent diffusion coefficient (ADC) values were not calculated. We performed a study that showed that ADC values are of interest in CJD diagnosis, as was previously suggested.2

We prospectively studied 20 patients with CJD (6 pathology-proved and 14 probable) and 10 age-matched controls. The codon 129 genotype was available for 15 subjects, who included 1 VV, 8 MM, and 6 MV subtypes. The MR imaging protocol included both fluid-attenuated inversion recovery (FLAIR) and diffusion sequences (DWI, *b* = 0, 500, 750, and 1000 s/mm2). In these patients, we found the same high frequency of lesions (15/15 on FLAIR and DWI), both on the cortex (13/15 on FLAIR, 15/15 on DWI) and on the basal ganglia (10/15 on FLAIR, 12/15 on DWI). The frequency of involvement of the striatum was similar on DWI in MM (6/8) and MV (5/6) genotypes. In addition, ADC values measured on the deep brain structures were significantly lower in patients with the MV and VV genotypes as compared with MM patients (*P* < .03 in the caudate, lenticular, and pulvinar nuclei; χ2 test). The difference was striking in the caudate nucleus, where ADC values were significantly different between controls and MM and MV/VV patients, with a clear-cut separation between MM and MV/VV patients (Fig 1). ADC values were not significantly different between controls and MM patients in the lenticular nucleus, despite the presence of signal-intensity changes on DWIs in 75% of these patients. These findings support a combination of different pathologic processes to explain the hypersignals observed on DWI, inducing increased and/or decreased diffusibility and emphasizing the added value of ADC measures to distinguish in vivo between molecular subtypes of CJD.

![ Fig 1. ](http://www.ajnr.org/http://ajnr-stage2.stage.highwire.org/content/ajnr/29/7/e57/F1.medium.gif)

[ Fig 1. ](http://www.ajnr.org/content/29/7/e57/F1)

 **Fig 1.**  
ADC values measured on the head of the caudate nuclei in patients with CJD with the MM (*n* = 8), MV (*n* = 6), and VV (*n* = 1, same column as MV, *triangle*) phenotypes and controls (*n* = 10). There is a statistical difference between all 3 groups (*P* < 10−4) and a clear-cut separation between patients with the MM and MV/VV phenotypes.

## References

1.  Tschampa HJ, Kallenberg K, Kretzschmar HA, et al. **Pattern of cortical changes in sporadic Creutzfeldt-Jakob disease.** AJNR Am J Neuroradiol 2007;28:1114–18
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo5OiIyOC82LzExMTQiO3M6NDoiYXRvbSI7czoxOToiL2FqbnIvMjkvNy9lNTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  Tschampa HJ, Murtz P, Flacke S, et al **Thalamic involvement in sporadic Creutzfeldt-Jakob disease: a diffusion-weighted MR imaging study.** AJNR Am J Neuroradiol 2003;24:908–15
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo4OiIyNC81LzkwOCI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yOS83L2U1Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

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