Right median nerve electrical stimulation for acute traumatic coma (the Asia Coma Electrical Stimulation trial): study protocol for a randomised controlled trial.

BACKGROUND: Traumatic brain injury (TBI) has become the most common cause of death and disability in persons between 15 and 30 years of age, and about 10-15% of patients affected by TBI will end up in a coma. Coma caused by TBI presents a significant challenge to neuroscientists. Right median nerve electrical stimulation has been reported as a simple, inexpensive, non-invasive technique to speed recovery and improve outcomes for traumatic comatose patients. METHODS/DESIGN: This multicentre, prospective, randomised (1:1) controlled trial aims to demonstrate the efficacy and safety of electrical right median nerve stimulation (RMNS) in both accelerating emergence from coma and promoting long-term outcomes. This trial aims to enrol 380 TBI comatose patients to partake in either an electrical stimulation group or a non-stimulation group. Patients assigned to the stimulation group will receive RMNS in addition to standard treatment at an amplitude of 15-20 mA with a pulse width of 300 µs at 40 Hz ON for 20 s and OFF for 40 s. The electrical treatment will last for 8 h per day for 2 weeks. The primary endpoint will be the percentage of patients regaining consciousness 6 months after injury. The secondary endpoints will be Extended Glasgow Outcome Scale, Coma Recovery Scale-Revised and Disability Rating Scale scores at 28 days, 3 months and 6 months after injury; Glasgow Coma Scale, Glasgow Coma Scale Motor Part and Full Outline of Unresponsiveness scale scores on day 1 and day 7 after enrolment and 28 days, 3 months and 6 months after injury; duration of unconsciousness and mechanical ventilation; length of intensive care unit and hospital stays; and incidence of adverse events. DISCUSSION: Right median nerve electrical stimulation has been used as a safe, inexpensive, non-invasive therapy for neuroresuscitation of coma patients for more than two decades, yet no trial has robustly proven the efficacy and safety of this treatment. The Asia Coma Electrical Stimulation (ACES) trial has the following novel features compared with other major RMNS trials: (1) the ACES trial is an Asian multicentre randomised controlled trial; (2) RMNS therapy starts at an early stage 7-14 days after the injury; and (3) various assessment scales are used to evaluate the condition of patients. We hope the ACES trial will lead to optimal use of right median nerve electrical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02645578 . Registered on 23 December 2015.

Predictive Validity and Inter-Rater Reliability of the Persian Version of Full Outline of Unresponsiveness Among Unconscious Patients with Traumatic Brain Injury in an Intensive Care Unit.

INTRODUCTION: The Glasgow Coma Scale (GCS) has some limitations when evaluating the unconscious patient. This study aims to validate the Persian version of the FOUR (Full Outline of Unresponsiveness) score as a proposed substitute. METHODS: Two nurses, two nursing students, and two physicians scored the prepared Persian version of the FOUR and GCS in 84 patients with acute brain injury. The inter-rater agreement for the FOUR and the GCS scores was evaluated by the weighted kappa (κ w). The outcome prediction power of the scales was assessed by the area under the curve (AUC) in the ROC curve. RESULTS: The inter-rater agreement of the FOUR was excellent (κ w = 0.923, 95 % CI, 0.874-0.971) and comparable with the one of the GCS (κ w = 0.938, 95 % CI, 0.889-0.987). The area under the curve (AUC) for predicting in-hospital mortality (modified Rankin Scale: 6) was 0.835 for the FOUR (95 % CI, 0.739-0.907) and 0.772 for the GCS (95 % CI, 0.668-0.856) (P = 0.01). AUC for predicting poor outcome (modified Rankin Scale: 3-6) for the total FOUR score was 0.983 (95 % CI, 0.928-0.999), which is comparable with 0.987 for the total GCS score (95 % CI, 0.934-1.000). CONCLUSIONS: The researchers conclude that the Persian version of the FOUR score is a reliable and valid scale to assess unconscious patients with traumatic brain injury and can be substituted for the GCS.

Long-lasting coma.

In this report, we describe the case of a patient who has remained in a comatose state for more than one year after a traumatic and hypoxic brain injury. This state, which we refer to as long-lasting coma (LLC), may be a disorder of consciousness with significantly different features from those of conventional coma, the vegetative state, or brain death. On the basis of clinical, neurophysiological and neuroimaging data, we hypothesize that a multilevel involvement of the ascending reticular activating system is required in LLC. This description may be useful for the identification of other patients suffering from this severe disorder of consciousness, which raises important ethical issues.

Long-term outcomes after shunt implantation in patients with posttraumatic hydrocephalus and severe conscious disturbance.

BACKGROUND: Posttraumatic hydrocephalus (PTH) is a frequent complication secondary to traumatic brain injury, especially among patients keeping chronic unconscious. And effects of shunt implantation on improving outcomes among these patients are still controversial. This study was aimed to assess the long-term outcomes following shunt implantation among patients who had PTH and kept chronic unconscious. METHODS: A prospective study was performed to include patients who had PTH and remained in severe conscious disturbance from March 2010 to December 2010. All of included patients would have shunt implantation and be closely followed up at least for 2 years to assess final outcomes. RESULTS: Fifteen patients having PTH were identified. Before shunt implantation, 2 patients kept vegetative state (Glasgow Outcome Scale [GOS] score 2), and 13 patients kept minimally consciousness with severe disability (GOS score 3). After shunt implantation, the shunt device was removed because of intracranial infection in 1 patient, and the other patient died because of allergic shock. Among the remaining 13 patients, finally 7 patients had improvement on GOS or Modified Barthel Index (MBI) score during the 2-year follow-up, but only 1 patient achieved a good outcome (GOS score 4, independent life). Among them, 5 patients' outcomes improved as assessed by GOS or MBI score during the first 3 months following shunt implantation. During the fourth to sixth month following shunt implantation, there were 2 patients who showed first rise on GOS or MBI score. Beyond 6 months, no patient showed initial improvement. And among patients who showed improvement, most of them kept improving during a certain time. CONCLUSIONS: A proportion of patients who had PTH and remained in severe conscious disturbance would benefit from shunt implantation, and the improvement may turn up late after this procedure.

[Neuroanatomical basis for traumatic coma: clinical and magnetic resonance correlates].

In this paper, the relationship between brain lesion localization (verified by magnetic resonance imaging (MRI)) and the severity of traumatic brain injury (TBI) and its outcomes is presented. Magnetic resonance studies in different modes (T1, T2, FLAIR, DWI, DTI, T2 * GRE, SWAN) were performed in 162 patients with acute TBI. Statistical analysis was done using Statistica 6, 8 software and R programming language. A new advanced MRI-based classification of TBI was introduced implying the assessment of hemispheric and brainstem traumatic lesions level and localization. Statistically significant correlations were found between the Glasgow coma and outcome scales scores (p < 0.001), and the proposed MRI grading scale scores, which means a high prognostic value of the new classification. The knowledge of injured brain microanatomy coming from sensitive neuroimaging, in conjunction with the assessment of mechanisms, aggravating factors and clinical manifestation of brain trauma is the basis for the actual predictive model of TBI. The proposed advanced MRI classification contributes to this concept development.

Functional MRI and outcome in traumatic coma.

Advances in task-based functional MRI (fMRI), resting-state fMRI (rs-fMRI), and arterial spin labeling (ASL) perfusion MRI have occurred at a rapid pace in recent years. These techniques for measuring brain function have great potential to improve the accuracy of prognostication for civilian and military patients with traumatic coma. In addition, fMRI, rs-fMRI, and ASL perfusion MRI have provided novel insights into the pathophysiology of traumatic disorders of consciousness, as well as the mechanisms of recovery from coma. However, functional neuroimaging techniques have yet to achieve widespread clinical use as prognostic tests for patients with traumatic coma. Rather, a broad spectrum of methodological hurdles currently limits the feasibility of clinical implementation. In this review, we discuss the basic principles of fMRI, rs-fMRI, and ASL perfusion MRI and their potential applications as prognostic tools for patients with traumatic coma. We also discuss future strategies for overcoming the current barriers to clinical implementation.

[The value of bispectral index in the unconscious patients with acute brain injury due to different pathogenic factors].

OBJECTIVE: To observe the differences in bispectral index (BIS) in unconscious patients with acute brain injury due to different pathogenic factors, and approach its clinical significance. METHODS: A retrospective study was conducted. One hundred and twenty-two unconscious patients with acute brain injured admitted to the intensive care unit (ICU) from March 2009 to August 2012 were involved. According to the pathogenic factors, all patients were divided into direct injury group (n=66) and indirect injury group (n=56). Based on BIS value, all patients were divided into the BIS<60 group (n=80) and the BIS≥60 group (n=42). The BIS was continuously measured for 12 hours during the first 3 days, or 24 hours after stoppage of sedative after admission to ICU. The mean value of BIS (BISmean) was evaluated. The acute physiology and chronic health evaluationII (APACHEII) score, probability of survival (PS) and Glasgow coma score (GCS) were recorded. On the same day, the serum protein S100 and neuron-specific enolase (NSE) were determined. The mortality and the rate of the poor neurological outcome were analyzed. RESULTS: (1) There were no significant differences in the age, sex, APACHEII score, PS and days of stay in ICU between the direct and indirect injury groups. (2) BISmean and GCS in direct injury group were significantly lower than those of the indirect injury group [BISmean: 39.0 (2.5, 58.0) vs. 59.0 (42.0, 71.0), GCS score: 3 (3, 5) vs. 4 (3, 6), both P<0.01], while serum S100 levels was significantly higher [2.30 (0.75, 6.66) mg/L vs. 0.84 (0.40, 3.62) mg/L, P<0.01]. There was no significant difference in the NSE level between the direct and indirect injury groups. (3) The mortality rate and poor neurological outcome rate in BIS<60 group were significantly higher than the BIS≥60 group (mortality rate: 67.50% vs. 40.48%, poor neurological outcome rate: 86.25% vs. 66.67%, P<0.01 and P<0.05). In the BIS<60 group, there were no significant differences in the mortality and poor neurological outcome rate between direct and indirect injury group. CONCLUSIONS: There are differences in pathogenic factors, the injury mechanism, and the degree of the brain injury between the direct and indirect injury groups. BIS monitoring could help judge the degree of different kinds of brain injury. BIS<60 indicates poor prognosis and neurological outcome in spite of the inducing factor of brain injury.

Disconnection of the ascending arousal system in traumatic coma.

Traumatic coma is associated with disruption of axonal pathways throughout the brain, but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness-arousal and awareness-in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. High angular resolution diffusion imaging tractography guided tissue sampling in the neuropathologic analysis. High angular resolution diffusion imaging tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical "awareness pathways." Neuropathologic examination, which used ß-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of high angular resolution diffusion imaging tract disruption. Axonal injury was also present within the gray matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain.

Self and parent ratings of executive functioning after adolescent traumatic brain injury.

OBJECTIVE: To examine the level of agreement between adolescents with traumatic brain injury (TBI) and their parents in standardized ratings of executive functioning, and to determine correlates of discrepancies between those ratings. PARTICIPANTS: Ninety-eight 11- to 16-year-old adolescents with TBI and their parents, and 97 neuropsychologically healthy controls. METHOD: Five-year consecutive series of rehabilitation referrals for TBI. MEASURES: Behavior Rating Inventory of Executive Function-Self Report (BRIEF-SR) and Behavior Rating Inventory of Executive Function (BRIEF) parent report versions. RESULTS: Self and parent ratings were moderately positively correlated in both the TBI group and the control group, but parents generally identified more executive dysfunction than did the adolescents. Parent-adolescent discrepancies were statistically significantly greater in the TBI group than in the control group on the Metacognitive index but not the Behavioral Regulation index. The degree of the former discrepancy was predicted by duration of coma in the TBI group. CONCLUSIONS: Adolescents with more severe TBI may underestimate their own degree of executive dysfunction in daily life, particularly aspects of metacognitive abilities, possibly, in part, because of an organic-based lack of deficit awareness.

Usefulness of functional MRI associated with PET scan and evoked potentials in the evaluation of brain functions after severe brain injury: preliminary results.

OBJECTIVE: To evaluate the feasability and the potential usefulness of functional MRI (fMRI) for the evaluation of brain functions after severe brain injury, when compared to a multimodal approach (evoked potentials [EP] and Positron Emission Tomography [PET] examinations). MATERIAL AND METHODS: Seven patients (mean age: 49 years [23-73], three males, four females) presenting with coma after acute severe brain injuries underwent fMRI (auditive, visual, somesthesic), (18)F-FDG PET and EP (auditive, visual, somesthesic) within a 3-day period of time in a mean of 120 days after initial brain injury. fMRI activations in somesthesic, visual and auditive cortical areas were compared to EP (28 possible comparisons) and to the metabolic activity on PET examination in the same anatomical areas (21 possible comparisons). RESULTS: In case of availability, results were concordant between fMRI and PET in 10 comparisons but not in one, and between fMRI and EP in 11 comparisons but not in four. CONCLUSIONS: In many patients, there is a good concordance between fMRI and brain functions suggested by EP and metabolic activity demonstrated with PET. In few others, fMRI can be integrated in the early evaluation of brain functions to further augment our capacity for a proper evaluation of brain functions in critically ill patients.

[Coma after lucid interval--severe secondary alteration of consciousness following multiple trauma]. / Koma nach luzidem Intervall--schwere sekundäre Bewusstseinseinschränkung nach Polytrauma.

A 71-year-old man sustains multiple fractures in an accident; after a lucid interval he deteriorates neurologically and becomes comatose. Intracranial hemorrhage, status epilepticus, adverse drug reactions, toxic-metabolic, ischemic or infectious causes are subsequently ruled out. Development of petechiae and thrombopenia raises the possibility of fat embolism syndrome, which is confirmed in a MRI of the head 72 hours after the accident. We discuss current aetiologic concepts as well as diagnosis and clinical course of the cerebral fat embolism syndrome.

Feasibility of instrumental swallowing assessments in patients with prolonged disordered consciousness while undergoing inpatient rehabilitation.

OBJECTIVE: To evaluate the feasibility, safety, and potential benefit of instrumental swallowing assessments for patients with prolonged disordered consciousness participating in rehabilitation. DESIGN: Case-control, retrospective. PARTICIPANTS: Thirty-five participants divided into 2 cohorts according to cognitive level at the time of baseline instrumental swallowing assessment. Group 1 (n = 17) participants were at Rancho Los Amigo (RLA) level II/III or RLA level III, while Group 2 (n = 18) participants were rated better than RLA level III. RESULTS: Aspiration and laryngeal penetration rates for both groups were similar (aspiration rate Group 1 = 41%, Group 2 = 39%; laryngeal penetration rate Group 1 = 59%, Group 2 = 61%). Overall, 76% (13/17) of Group 1 and 72% (13/18) of Group 2 were able to receive some type of oral feedings following baseline video fluoroscopic swallow study (VFSS) or endoscopic exam of the swallow (FEES). CONCLUSION: The majority of participants who underwent an instrumental swallowing examination while still functioning at RLA level II/III or RLA level III were able to return to some form of oral feedings immediately following their baseline examination. Swallowing as a treatment modality can be considered a part of the overall plan to facilitate neurobehavioral recovery for patients with prolonged disordered consciousness participating in rehabilitation.

Neuroimaging and the vegetative state: resolving the behavioral assessment dilemma?

The accurate assessment of patients with impaired consciousness following a brain injury often remains a challenge to the most experienced clinician. A diagnosis of vegetative or minimally conscious state is made on the basis of the patient's clinical history and detailed behavioral examinations, which rely upon the patient being able to move or speak in order to demonstrate residual cognitive function. Recently, the development of noninvasive neuroimaging techniques has fostered a rapid increase in the exploration of residual cognitive abilities in these patient populations. However, while this body of literature is growing rapidly, at present the enterprise remains one of scientific endeavor with no inclusion in standard clinical practice. Correctly administered behavioral testing in survivors of brain injury may provide sufficient information to identify patients who are aware and are able to signal that this is the case via a recognized motor output. However, it remains possible that a subgroup of these patients may retain some level of awareness, but lack the ability to produce any motor output and are therefore mistakenly diagnosed as vegetative. It is in this latter situation that functional neuroimaging may prove to be most valuable, as a unique clinical tool for probing volition and residual cognition without necessarily assuming that the patient is able to produce any motor output.

Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders.

PRIMARY OBJECTIVE: This study investigates (1) the utility of the bispectral index (BIS) to distinguish levels of consciousness in severely brain damaged patients and, particularly, disentangle vegetative state (VS) from minimally conscious state (MCS), as compared to other EEG parameters; (2) the prognostic value of BIS with regards to recovery after 1 year. RESEARCH DESIGN: Multi-centric prospective study. METHOD AND PROCEDURES: Unsedated patients recovering from coma were followed until death or transferal. Automated electrophysiological and standardized behavioural assessments were carried out twice a week. EEG recordings were categorized according to level of consciousness (coma, VS, MCS and Exit MCS). Outcome was assessed at 1 year post-insult. MAIN OUTCOMES AND RESULTS: One hundred and fifty-six EEG epochs obtained in 43 patients were included in the analyses. BIS showed a higher correlation with behavioural scales as compared to other EEG parameters. Moreover, BIS values differentiated levels of consciousness and distinguished VS from MCS while other EEG parameters did not. Finally, higher BIS values were found in patients who recovered at 1 year post-insult as compared to patients who did not recover. CONCLUSION: EEG-BIS recording is an interesting additional method to help in the diagnosis as well as in the prognosis of severely brain injured patients recovering from coma.

Search for clinical and neurophysiological prognostic patterns of brain coma outcomes in children.

OBJECTIVE: The aim of the study was to evaluate the possible predictive values of clinical examinations combined with the recordings of electroencephalography and brainstem auditory-evoked potentials in traumatic coma of pediatric patients. MATERIAL AND METHODS: A total of 43 children in coma with severe acute head trauma were included in the study. They were investigated and treated in pediatric intensive care unit using standard evaluation and treatment protocol. Evaluation of coma was performed using Glasgow Coma Scale. Electroencephalography for 35 patients and brainstem auditory-evoked potentials for 24 patients were recorded. RESULTS: Glasgow coma scale statistic pool median was equal to 4 points as measured in presence of brain edema, meanwhile it was 6 as measured in absence of edema. In case of supratentorial damage, median duration of consciousness recovery was 10 days. In absence of above-mentioned supratentorial damage, recovery of the consciousness was earlier - median was 5 days. Determined duration of artificial lung ventilation was statistically significantly shorter for those who had edema (P=0.048). In 20 patients (57% of all cases), constant or alternating slow wave activity was observed during the first electroencephalographic recording. In other cases, "alpha coma" or low amplitude of arrhythmic activity and local slowing activity corresponding to brain damage seen on computerized tomography were recorded. For 24 patients, brainstem auditory-evoked potentials were recorded. In 9 cases, they were abnormal; in these cases, the consciousness of the patients recovered after 44 days or did not recover. CONCLUSIONS: Glasgow coma scale results alone may have limited prognostic value in absence of other objective neurophysiologic investigation data concerning the coma outcome in children. Prognosis may be worse if pathological brainstem auditory-evoked potentials correlate with pathological dynamic changes in electroencephalography and brain lesions, diagnosed during computerized tomography scan.

Comparison of indices of traumatic brain injury severity: Glasgow Coma Scale, length of coma and post-traumatic amnesia.

BACKGROUND: Classification of traumatic brain injury (TBI) severity guides management and contributes to determination of prognosis. Common indicators of TBI severity include Glasgow Coma Scale (GCS) scores, length of coma (LOC) and duration of post-traumatic amnesia (PTA). OBJECTIVE: To compare GCS, LOC and PTA by examining distributions and intercorrelations and develop multivariable linear regression models for estimating LOC and PTA duration. METHODS: Prospective study of 519 of 614 consecutive patients with TBI. Indices of TBI severity studied were GCS, LOC, PTA and PTA-LOC (the interval from return of command-following to return of orientation). Candidate predictor variables for estimation of LOC, PTA and PTA-LOC intervals were age, years of education, year of injury (before 1997 vs 1997 or later), GCS, LOC (for PTA and PTA-LOC), pupillary responsiveness, type of injury, CT pathology and intracranial operations. RESULTS: Although there was a severity/response relationship between GCS and LOC, PTA and PTA-LOC intervals, there was overlap in these intervals between GCS severity categories. Age, year of injury, GCS, pupillary responsiveness and CT pathology were predictive of LOC. Age, years of education, year of injury, GCS, LOC, pupillary responsiveness and intracranial operations were predictive of PTA duration. Age, years of education, year of injury, GCS, LOC and pupillary responsiveness were predictive of PTA-LOC. GCS and LOC effects were influenced by age. CONCLUSIONS: Predictors for estimating LOC, PTA and PTA-LOC intervals were determined and simple equations were developed. These equations will be helpful to clinicians, researchers and those counselling family members of patients with TBI.