Limitations.
The reliability of PPT measurements is dependent upon not only the application technique of the observer, but also on the ability of the participant to provide a consistent verbal indication of the PPT level. It has been previously shown in ME/CFS patients that working memory, as assessed by n-back testing, is reduced during-HUT compared to pre-HUT(44, 45). This may have altered the post-HUT assessment of PPT and windup. For reasons of impaired memory and concentration we applied 1 kg/s instead of 2 kg/s in determining windup, as patient responses might be delayed(35). For the same reason we asked patients to rate windup after every stimulus. Whether this may change the outcomes, needs to be studied in future. The reduction of cerebral blood flow during HUT(50) is variable between ME/CFS patients. To which extent the cerebral blood flow reduction is related to PPT changes is subject of another study. We only studied ME/CFS patients undergoing HUT because of the suspicion of OI. It is unknown whether ME/CFS patients without OI show the same PPT and windup alterations. Also, the effect in male ME/CFS patients is unknown. This single center study is the first on the effects of HUT on PPT and windup and needs to be replicated by others.