PKD or Not PKD: That is the question

active demyelination, hence with more dynamic endogenous remyelination that might be detected by PET. Interestingly, Mat ıas-Guiu and collaborators, using the stilbene derivative F-florbetaben and a semiquantitative approach, found a lower uptake in the progressive types of MS compared to RRMS, suggesting that disease progression may be associated with a persistent and cumulative process of myelin loss in the white matter. The key remaining question is whether the individual remyelination profiles that were detected using C-Pittsburgh compound B (C-PiB) PET have the potential to influence the long-term disease evolution. The population investigated had a 7.45-year mean disease duration, and the remyelination profiles were highly correlated with disability. In particular, a strong correlation was found between the index of dynamic remyelination and the MS severity scale scores, which take into account the disease duration: this suggests that remyelination significantly influenced the accrual of medium-term disability during the RRMS phase. To establish the relationship with disability in the long term, it will be necessary to further follow up subjects, and to develop similar longitudinal studies in the later stages of the disease, especially over the course of progressive MS. The uptake of the tracer in inflammatory conditions has been questioned, and in the context of cerebral amyloid angiopathy Carmona-Iragui et al described a milder amyloid uptake in swollen areas. Contrasting with this finding, we showed a milder uptake reduction in gadolinium-enhancing inflammatory lesions compared to overall T2 lesions. Therefore, in MS, which is a nonamyloid disease, the inflammatory component does not seem to negatively bias the estimation of the myelinbound fraction. Furthermore, any bias linked to active lesions was minimized, as only 4% of the T2 lesional volume analyzed by Bodini et al was made of gadolinium-enhancing lesions. Finally, we carefully quantified the C-PiB binding in the normal-appearing white matter (NAWM) of patients and found no difference with the white matter of control subjects. This contrasts with the report of Mat ıas-Guiu et al, which described a reduced uptake in the NAWM, a difference that could be explained by the inclusion of progressive patients in their cohort (7 of 12 patients). It would be of potential clinical interest to use the level of tracer binding the NAWM to discriminate RRMS from progressive MS. However, some methodological issues may have influenced Mat ıas-Guiu’s findings. First, in their study, only 3 subjects were included as healthy controls. Second, Mat ıas-Guiu’s study was not conducted with dynamic acquisitions, as only static standardized uptake values (SUVs) were employed to measure F-florbetaben uptake; this could represent a limit in the interpretation of the results, as it has been shown for C-PiB that using SUVs leads to a higher intersubject variability and less reproducibility. Finally, in our study, perilesional regions were excluded from the NAWM analysis, as C-PiB binding in those regions was significantly reduced compared to NAWM. It would therefore be of great interest to confirm Mat ıas-Guiu’s results after the exclusion of perilesional regions from the NAWM. Overall, the application to MS of PET imaging with either stilbene or benzothiazole derivatives, especially those that may be labeled with fluorine-18, is a promising emerging field of research that may extend the investigations to larger cohorts and improve our understanding of the disease physiopathology. Ultimately, this approach will allow the evaluation of candidate drugs aimed at promoting remyelination.