In this geographically-diverse sample drawn from a Belgian federal network of brain injury treatment centers, the rate of misdiagnosis of VS (41%) is roughly equivalent to rates reported in the U.S. and U.K. before the criteria for MCS were published [5, 6]. Misdiagnosis occurred most often as the result of failure to detect purposeful eye movements (i.e., visual fixation and pursuit), in line with previous studies . Moreover, our study suggests that the majority of cases with an uncertain diagnosis are in MCS (89%), not in VS. Finally, a false negative diagnosis of MCS was noted in 10% of cases that had emerged from this condition.
One could argue that the false negative consensus-based MCS diagnoses actually represent false positive CRS-R diagnoses of MCS. This possibility cannot be excluded but is also not easily resolved. As false positive errors increase, specificity decreases. However, in the context of a weak gold standard, false positives may not actually reflect diagnostic errors. If we consider the clinical consensus diagnosis as the gold standard, then false positive errors on the comparison measure (i.e., diagnosis of MCS) will result in lower specificity. Such false positive errors may, however, be due to the superior capacity of the comparison measure to detect the behavior of interest. In this case, the CRS-R, a standardized measure, captured more behavioral signs of consciousness relative to the collective impression of the medical team. One could also argue that there was a bias in favor of the research team's diagnostic accuracy as the researchers were not blind to the consensus diagnosis. The research team's knowledge of the clinical consensus diagnosis may hence have overestimated the sensitivity of CRS-R to detect signs of consciousness. However, the CRS-R requires replication of behavioral responses before scoring them as present (e.g., a response to verbal order is considered scoreable if the appropriate behavior is observed on 3 out of 4 trials) and, as such, decreases the risk of a false positive diagnosis. Future studies including blind assessment could be performed in order to comfort our results.
Spontaneous recovery is unlikely to explain our results as the clinical consensus diagnosis included behaviors observed by the medical staff within the prior 24 hours and was provided just before the CRS-R assessment. It is more likely that the examiners' reliance on unstructured bedside observations contributed to the high rate of misdiagnosis of VS patients. Indeed, it has been suggested that misdiagnosis is influenced by the use of a standardized behavioral tool . In this study, we compared the accuracy of diagnoses based on standardized behavioral assessment using the CRS-R with consensus-based diagnoses established by the medical team following qualitative observations. Unlike traditional bedside assessment, the CRS-R guards against misdiagnosis by incorporating items that directly reflect the existing diagnostic criteria for MCS, and by operationalizing scoring criteria for the identification of behaviors associated with consciousness. Standardized assessment approaches may hence mitigate the tendency to miss signs of consciousness that may arise when the diagnosis is based solely on routine bedside examination. In cases with ambiguous behavioral findings, the failure to employ a standardized behavioral tool may increase the likelihood of misdiagnosis. Reliance on qualitative (versus standardized) assessment could also explain the higher rate of misdiagnosis observed for VS and MCS patients in both chronic and acute care settings. There is evidence to support this premise. Data regarding the use of a standardized behavioural scale were collected for each centre involved in this study. The behavioural scales' scores were not reported to the research team but were taken in account for the clinical consensus diagnosis. All 46 patients in the acute setting were evaluated with the Glasgow Coma Scale, a standardized assessment tool, and only 4 of these cases (10%) were misdiagnosed. In contrast, of the 57 chronic patients, 30 were not assessed using a standardized measure and 9 cases (30%) were misdiagnosed.
Finally, for uncertain diagnoses, we did not collect information on who disagreed and how frequently. While it would be helpful to know if uncertain diagnoses were due to the ambiguity of patient's responses or to the observational skills of the examiner, the aim of this study was to assess the misdiagnosis rate rather than explain the causes of misdiagnosis.