Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment

BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). METHODS: We prospectively followed 103 patients (55 +/- 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' RESULTS: Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. CONCLUSION: Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus

Minimally conscious state “plus”: diagnostic criteria and relation to functional recovery

peer reviewedBackground: We investigated the relationship between three language-dependent behaviors (i.e., command-following, intelligible verbalization, and intentional communication) and the functional status of patients with disorders of consciousness (DoC). We hypothesized that patients in minimally conscious state (MCS) who retain behavioral evidence of preserved language function would have similar levels of functional disability, while patients who lack these behaviors would demonstrate significantly greater disability. We reasoned that these results could then be used to establish empirically-based diagnostic criteria for MCS+. Methods: In this retrospective cohort study we included rehabilitation inpatients diagnosed with DoC following severe-acquired brain injury (MCS = 57; vegetative state/unresponsive wakefulness syndrome [VS/UWS] = 63); women: 46; mean age: 47 ± 19 years; traumatic etiology: 68; time post-injury: 40 ± 23 days). We compared the scores of the Disability Rating Scale score (DRS) at time of transition from VS/UWS to MCS or from MCS– to MCS+, and at discharge between groups. Results: Level of disability on the DRS was similar in patients with any combination of the three language-related behaviors. MCS patients with no behavioral evidence of language function (i.e., MCS–) were more functionally impaired than patients with MCS+ at time of transition and at discharge. Conclusions: Command-following, intelligible verbalization, and intentional communication are not associated with different levels of functional disability. Thus, the MCS+ syndrome can be diagnosed based on the presence of any one of these language-related behaviors. Patients in MCS+ may evidence less functional disability compared to those in MCS who fail to demonstrate language function (i.e., MCS–). © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Functional Brain Imaging in the Clinical Assessment of Consciousness

Recent findings suggest that functional brain imaging might be used to identify consciousness in patients diagnosed with persistent vegetative state and minimally conscious state. Michael Rafii and James Brewer discuss the potential for fMRI's wider implementation in clinical practice, and associated caveats

Disorders of Consciousness

Disorders of Consciousness are a big challenge for the entire process of rehabilitation: assessment, diagnosis, pharmacological, and rehabilitation programs, including conventional treatments and the use of new technologies

Single tDCS session of motor cortex in patients with disorders of consciousness: a pilot study

peer reviewedPrimary Objective: Patients with disorders of consciousness (DOC) face a lack of treatments and risk ofmisdiagnosis, potentially due to motor impairment. Transcranial direct current stimulation (tDCS)showed promising results over the prefrontal cortex in DOC and over the primary motor cortex (M1)in stroke. Tis pilot study aimed at evaluating the behavioral effects of M1 tDCS in patients with DOC.Research Design: In this randomized double-blind sham-controlled crossover trial, we included 10patients (49 ± 22 years, 7 ± 13 months since injury, 4 unresponsive wakefulness syndrome, 6 minimallyconscious state, 5 traumatic etiologies).Methods and Procedures: One session of tDCS (2 mA for 20 min) and one session of sham tDCS wereapplied over M1 in a randomized order with a washout period of minimum 24 h and behavioral effectswere assessed using the CRS-R. At the group level, no treatment effect was identified on the total score(p= .55) and on the motor subscale (p= .75). Two patients responded to tDCS by showing a new sign ofconsciousness (visual pursuit and object localization).Conclusions: One session of M1 tDCS failed to improve behavioral responsiveness in patients with DOC.Other application strategies should be tested

Detecting Awareness in the Vegetative State: Electroencephalographic Evidence for Attempted Movements to Command

Patients in the Vegetative State (VS) do not produce overt motor behavior to command and are therefore considered to be unaware of themselves and of their environments. However, we recently showed that high-density electroencephalography (EEG) can be used to detect covert command-following in some VS patients. Due to its portability and inexpensiveness, EEG assessments of awareness have the potential to contribute to a standard clinical protocol, thus improving diagnostic accuracy. However, this technique requires refinement and optimization if it is to be used widely as a clinical tool. We asked a patient who had been repeatedly diagnosed as VS for 12-years to try to move his left and right hands, between periods of rest, while EEG was recorded from four scalp electrodes. We identified appropriate and statistically reliable modulations of sensorimotor beta rhythms following commands to try to move, which could be significantly classified at a single-trial level. These reliable effects indicate that the patient attempted to follow the commands, and was therefore aware, but was unable to execute an overtly discernable action. The cognitive demands of this novel task are lower than those used previously and, crucially, allow for awareness to be determined on the basis of a 20-minute EEG recording made with only four electrodes. This approach makes EEG assessments of awareness clinically viable, and therefore has potential for inclusion in a standard assessment of awareness in the VS

Pathological Computed Tomography Features Associated with Adverse Outcomes after Mild Traumatic Brain Injury:A TRACK-TBI Study with External Validation in CENTER-TBI

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI.98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up

A Manual for the Glasgow Outcome Scale-Extended Interview

The Glasgow Outcome Scale-Extended (GOSE) has become one of the most widely used outcome instruments to assess global disability and recovery after traumatic brain injury. Achieving consistency in the application of the assessment remains a challenge, particularly in multi-center studies involving many assessors. We present a manual for the GOSE interview that is designed to support both single- and multi-center studies and promote inter-rater agreement. Many patients fall clearly into a particular category; however, patients may have outcomes that are on the borderline between adjacent categories, and cases can present other challenges for assessment. The Manual includes the general principles of assessment, advice on administering each section of the GOSE interview, and guidance on “borderline” and “difficult” cases. Finally, we discuss the properties of the GOSE, including strengths and limitations, and outline recommendations for assessor training, accreditation, and monitoring

Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques

In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world, practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as 43%) - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation of residual function, formation of differential diagnoses, and estimation of prognosis