Multicenter prospective study on predictors of short-term outcome in disorders of consciousness

Abstract

Objective.This international multi-center, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged Disorders of Consciousness (DoC) due to acquired severe brain injury.Methods.Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical and neurophysiological data were collected at study entry. Patients were then followed-up for assessing the primary outcome, i.e. clinical diagnosis according to standardized criteria at 6 months post-injury.Results.We enrolled 147 patients (44 women; mean age: 49.4 [95% confidence intervals: 46.1-52.6] years; VS/UWS= 71, MCS= 76; traumatic= 55, vascular= 56, anoxic= 36; mean time post-injury= 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS= 70; MCS= 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS= 27; MCS= 45). Younger age, shorter time post-injury, higher Coma Recovery Scale-Revised total score and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity and P300 on event related potentials were not associated with outcome.Conclusions.Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families and funding sources with various aspects of decision-making. This multi-center, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC.

When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress

“…The results of the latest studies with representative samples seem to evidence that around half of the patients who are admitted in a UWS, remain in this condition 6 months after the injury [ 23 , 34 ]. The higher proportion of patients in UWS at admission in our study by that time could be explained by the fact that patients were admitted to our facilities, and our study, with up to one year post-injury, while only patients with less than three months of evolution were included in the other studies [ 23 , 34 ]. However, transition to MCS at 6 months since injury was detected, as in our study, in almost one third of patients [ 23 , 34 ].…”

“…However, the reliability of these figures has been questioned because they include retrospective old series of patients that could not represent the current state of the clinical practice [ 13 ]. Since then, a large number of studies have described the neurobehavioral progress of patients with UWS, often showing large discrepancies between studies, which can be partially explained by differences in the methodologies and included samples [ 23 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Some studies have also investigated demographic, clinical and neurophysiological predictors of the neurobehavioral progress in patients with DOC, with a particular emphasis on patients with UWS.…”

“…Some studies have also investigated demographic, clinical and neurophysiological predictors of the neurobehavioral progress in patients with DOC, with a particular emphasis on patients with UWS. Factors such as age, etiology, injury location and the baseline time since injury, neurobehavioral condition, and level of disability have been associated with neurobehavioral outcomes of patients with DOC [ 29 , 33 , 34 , 35 , 36 , 37 , 38 , 41 , 46 , 47 , 49 ]. Neurophysiological metrics as well as responses to neuroimaging active and passive paradigms, have been also shown to be associated with patients’ prognosis [ 23 , 34 , 39 , 40 , 49 , 50 ].…”

“…Although all the existing studies provide valuable information about the neurobehavioral progress of patients with UWS, they incorporate small samples [ 26 , 27 , 30 , 31 , 32 , 35 , 37 , 47 , 49 , 50 ], include infrequent assessments [ 23 , 29 , 33 , 34 , 37 , 38 , 40 , 41 , 42 , 50 ], do not use standardized neurobehavioral assessment measures [ 26 , 27 , 43 ] (contrary to updated recommendations [ 3 , 44 ]), focus on patients with specific etiologies [ 31 , 36 , 39 , 50 ], combine data with those from patients with MCS [ 23 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 41 , 46 , 47 , 49 ], and, except on rare occasions [ 37 , 42 , 45 ], provide information about behavioral signs. In addition, with regards to the studies on predictors, most of the existing studies described to date do not provide the parameters of the models [ 23 , 29 , 33 , 36 , 37 ,...…”

“…While the medical records of patients with UWS are limited and clinical procedures differ across clinical facilities, models should be, at least, internally validated with resampling methods, such as cross validation or bootstrapping. A recent international multicenter collaboration by the International Brain Injury Association’s DOC Special Interest Group is noteworthy for overcoming this recurring methodological limitation [ 34 ]. However, the study include data from patients either with UWS or in MCS who may or may not be undergoing rehabilitation and are followed for less than six months.…”