The main objective of this study was to investigate the misdiagnosis rate of clinical consensus compared to repeated behavior scale assessments. After the single CRS-R behavior evaluation, it was found that the misdiagnosis rate of clinical MCS was 24.7%, while the repeated CRS-R evaluation results showed that the misdiagnosis rate of clinical MCS was 38.2%. A total of 16.7% of EMCS patients was misdiagnosed as MCS, and 1.1% of EMCS patients was misdiagnosed as UWS.
For the evaluation of the consciousness level of patients with prolonged DOC, a large number of previous studies has compared the diagnostic results of the standard CRS-R scale with other scales, and it has been found that the CRS-R scale has a high sensitivity in detecting the consciousness of patients with MCS or EMCS [36, 37]. When the CRS-R scale is used, it can be found that many patients with a clinical consensus diagnosis of unconscious actually remain minimally conscious. Schnakers et al. found that 41% of patients with a clinical consensus diagnosis of UWS was actually found to be MCS patients after an evaluation using the standard CRS-R behavior scale, whereas the clinical consensus is that 10% of patients with MCS are actually higher conscious EMCS (fully conscious) [22]. A recent study on repeated CRS-R behavior assessments showed that the clinical consensus still had a 33% misdiagnosis rate when diagnosing MCS patients [23]. This also supports the results of the current study. It was found that repeated behavioral assessments could identify patients with MCS with a high misdiagnosis rate of 38.2%. Moreover, the misdiagnosis rate of EMCS with full consciousness was 16.7%. When the evaluation results of the single CRS-R scale were compared with the clinical consensus, it was found that 24.7% of patients were misdiagnosed with MCS by clinical consensus, which was significantly lower than the previous studies on the misdiagnosis rate at 41%; however, the 14.6% misdiagnosis rate of EMCS was similar to the 10% misdiagnosis rate in a previous study [22]. During this decade, with the continuous progress in the field of prolonged DOC, clinicians have a deeper understanding of this concept. This may be the reason for the significant difference in the misdiagnosis rate over the past 10 years. In addition, the difference between single assessment and repeated assessment emphasizes that the fluctuations of patients' responsiveness have an effect on the neuro-behavioral assessment, and also emphasizes the importance of repeated assessment in the clinical diagnosis.
When whether the patient’s demographic factors would lead to clinical misdiagnosis was analyzed, it was found that the difference in gender, etiology, age groups and post-injury time was not the reason for the clinical consensus misdiagnosis. Therefore, it is highly likely that the clinical worker is highly dependent on the patients’ bedside behaviors in the patients’ daily management and may not be using systematic and standardized behavioral assessment tools to diagnose awareness. In addition, it was found that the Glasgow Coma Scale (GCS) was widely used for almost all patients admitted to the hospital, and a previous study also showed that the scale was not appropriate for assessing a patient’s level of consciousness [24]. Different from the GCS scale, the CRS-R scale has very clear MCS diagnostic criteria, and the evaluation consciousness from various angles can be used to diagnose the consciousness level of patients more sensitively, which greatly reduces the misdiagnosis of patients with prolonged DOC. Therefore, the use of standardized CRS-R assessment tools is particularly important for the detection of clinical patients’ level of consciousness and patient management.
During the implementation of the standardized CRS-R scale, a large number of studies has found that the standard CRS-R scale still has some misdiagnosis rates. Cheng and Gosseries et al. found that the name of the patient is more suitable for the detection of auditory localization than other sound stimuli [38]. Vanhaudenhuys et al. also found that the best way to check visual pursuit in MCS patients is to use a moving mirror rather than a moving object or person [39, 40]. Therefore, the application of personally related visual and auditory stimulation can better reduce the misdiagnosis rate of patients compared with natural stimulation [34]. In addition, when the CRS-R was used to evaluate the use of functional objects for MCS patients, the use of personalized objects seemed to elicit better responses from patients, thereby identifying misdiagnosed EMCS [33]. For this study, repeated CRS-R behavior assessments were employed, during which family members or caregivers were asked about patients’ items of interest. To better elicit the patients’ responses according to the patients’ preferences, a variety of different stimuli were selected according to the patients’ performance during the evaluation process, namely natural stimuli and personally related stimuli. It was found that when patients were diagnosed with MCS based on the first behavior evaluation, most of them showed signs of consciousness on the visual subscale (72.7%) and the motor subscale (54.5%), and few showed signs of consciousness on the auditory subscale (9.1%) and the communication scale (4.5%). After repeated evaluations, 10 patients showed signs of consciousness for visual subscale, four patients with motor subscale signs of consciousness, and two patients with auditory subscale signs of consciousness. This is most likely due to fluctuations in the patients’ levels of arousal or consciousness and due to the use of the patients’ own associated stimuli.
It was also found that for the vast majority of patients diagnosed with MCS, the items showing signs of consciousness were mainly related to the visual subscale (visual pursuit and visual fixation), the motor subscale (automatic motor response and localization to noxious stimulation), and the auditory subscale (reproducible movement to command). The results were confirmed by a previous study [41], but the difference is that the most sensitive item in this study was the visual subscale, while the most sensitive item in the previous study was the reproducible movement to command items on the auditory subscale.
Based on the results, it was found that the clinical consensus had a higher rate of misdiagnosis, especially compared to repeated CRS-R scales. This also highlights the importance of the CRS-R scale in the assessment of patient consciousness. Therefore, it is suggested that for patient daily management, clinicians should at least evaluate visual pursuit and visual fixation for the visual subscale, automatic motor response and localization to noxious stimulation for the motor subscale, and reproducible movement to command for the auditory subscale when assessing patients’ levels of consciousness. This can greatly reduce the misdiagnosis rate of patients, although for patients with prolonged DOC, the bedside neurobehavioral assessment has some limitations, and neuroimaging is considered an important method for the diagnosis of consciousness [23]; however, a behavioral assessment is still the most direct and portable method and should be promoted in clinical practice.
The limitation of this study was that no neuroimaging methods were used to evaluate the enrolled patients with prolonged DOC. Because the CRS-R scale still has some false negatives, behavioral assessments combined with neuroimaging should be used to truly understand the misdiagnosis rate of a clinical consensus in the future. Besides, we did not analyze the difference in regards to complications in patients with prolonged DOC during hospitalization which may play a role for the results, and we can analyze this factor in the future studies.