Discussion
CRS-R, sepsis, spasticity, RTT
SEPSIS, SECONDARY, STILL
To the authors’ knowledge, this is the first randomized-controlled trial among patients with DoC using a RTT with built-in FES of the lower extremities. The primary goal of this study was to test whether RTT treatment was associated with improved recovery of consciousness compared to CPT as part of a comprehensive neurorehabilitation program. RTT with or without FES was equally effective as CPT in promoting recovery of consciousness. We found indirect evidence, that time spent in an upright body position was significantly correlated with the extent of recovery of consciousness at end of treatment and marginally significantly at follow-up. These results could be a hint for a beneficial effect of daily verticalization over 60° on LoC, pertaining up to 5 months after treatment. The significant correlation between recovery until the end of treatment and verticalization across groups could be a result of the strong and highly significant correlation within the RTT-F subgroup. This could be explained by longer verticalization times above 60° position in the RTT-F compared to the RTT+F and CPT groups, that may have been caused by longer preparation times in the RTT+F (due to placement of FES electrodes) and CPT (due to stabilization at bedside through therapists) subgroups, and consequently less verticalization time. We tested whether RTT+F and CPT treatment were less effective by comparing the mean verticalization times per session across groups. The RTT groups had comparable verticalization times, which were significantly longer than the CPT groups. The efficiency of the RTT treatment with regard to net therapy time is in line with previous research [A recent meta-analysis of different verticalization treatments in patients with DoC found only partial evidence for the effectiveness of verticalization treatment regimes [Still the question arises, whether the reported rate of recovery was clinically meaningful. Ng and King [Recovery on secondary clinical outcomes (gain in functional independence during the treatment or change in the degree of spasticity of upper and lower limbs) was not better in the RTT groups compared to the CPT group. The RTT+F and the CPT group showed overall higher changes than the RTT-F (see Table We did not find an effect on EEG beta band power, after RTT treatment, as did a study on the effect of the verticalization on beta power in the injured hemisphere of MCS patients [The biggest limitation of this study is the absence of a treatment arm without any kind of verticalization or mobilization except of standard therapy. Earlier work reported positive evidence for RTT treatments [Further, as pointed out above, the number of treatment sessions was greatly imbalanced, thus limiting the conclusions that can be drawn from this study. A possible explanation of the RTT groups having significantly less sessions than the control group could be the higher amount of protocol deviations in the RTT groups than in the control group.Similarly, the time post-injury (TPI) was not well-balanced between groups, with the longest interval in the RTT-F group, whereas the TPI was quite similar in the RTT+F and CPT groups. At closer inspection, this imbalance is most likely caused by two potential outliers in the RTT-F group with very long TPI. Still, it is unlikely that these two outliers might have influenced the results in a negative way, as one of them had improved in LoC at T4 and one had not.Another limitation of this study is the lack of blinding in outcome assessors. Blinding of researchers was not feasible during verticalization sessions (T1), however, for outcome assessments (CRS-R, NCS-R, MAS, FIM and EEG analysis) it would have been beneficial to have blinded assessors. A meta-analysis reported that in 8/10 articles there was no blinding of outcome assessors [In this study the most frequent reason for an interruption or premature stop of the treatment protocol was transferring patients back to acute-setting hospitals (e.g., for ventriculo-peritoneal shunting or sepsis). Minor deviations from the protocol occurred more often in the RTT groups than in the CPT group and could have limited the effectiveness of the Erigo®Pro-based treatment in improving consciousness. This must be investigated in more detail in future studies.