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-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.

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.

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.

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.

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.

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.

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Predicting one year clinical outcome in traumatic brain injury (TBI) at the beginning of rehabilitation.

Predicting long-term clinical outcome for patients with traumatic brain injury (TBI) at the beginning of rehabilitation provides essential information for counseling of the family and priority-setting for the limited resources in intensive rehabilitation. The objective of this study is to work out the probability of the one-year outcome at the beginning of rehabilitation. Sixty-eight patients with moderate-to-severe TBI and known one-year outcome were employed for outcome prediction using the logistic regression model. A large number of prospectively collected data at admission (age, Glasgow Coma Scale [GCS] Score, papillary response), during intensive care unit (ICU) management (duration of coma, intracranial pressure [ICP] and its progress) and at the beginning of rehabilitation (baseline Functional Independence Measure [FIM], Neuro-behavioral Cognitive Status Examination [NCSE] and Functional Movement Assessment [FMA]) were available for preliminary screening by univariate analysis. Six prognostic factors (age, GCS, duration of coma, baseline FIM, NCSC and FMA) were utilized for the final logistic regression model. Age, GCS and baseline FIM at the beginning of rehabilitation have been found to be independent predictors for one-year outcome. The accuracy of prediction for a good Glasgow Outcome Score is 68% and an outcome for disability (either moderate or severe) is 83%. Validation of this model using a new set of data is required.

[Cerebral circulatory autoregulation as a guide for controlling the parameters of assisted ventilation in acute severe brain injury].

The paper presents the results of cerebral circulation (CC) in 17 ventilated patients with severe brain injury in its acute phase. All the patients developed traumatic subarachnoidal hemorrhage, which was accompanied with angiospasm in the majority of cases. Doppler transcranial study (DTCS) was performed, by using the carotid compression test; the findings correlated with paCO2 and CV parameters. A dynamic study was performed every two days starting from their admission to an intensive care unit to the recovery from coma or normalization of CC parameters. The dilation and constriction components of the CC reserve were assessed from the results of this test and continued to be controlled during therapy. Thus, this paper shows the possibility of goal-oriented correction of CC autoregulation and optimization by selecting the parameters of assisted ventilation and by changing paCO2 under the guidance of Doppler transcranial study.

Functional MR imaging assessment of a non-responsive brain injured patient.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Patients who talk and deteriorate: a new look at an old problem.

BACKGROUND AND METHODS: We sought to review established prognostic indicators applied to Asian population, and to identify new risk factors for deterioration in patients who talked and deteriorated after traumatic brain injury (TBI). This retrospective study used our prospectively maintained TBI database. From August 1999 to July 2001, 324 patients were admitted to the neurosurgical intensive care unit (ICU). Thirty-eight patients (11.8%) talked between injury and subsequent deterioration into coma. Independent outcome predictors were studied. RESULTS AND CONCLUSION: Fourteen patients had subdural haematomas, 9 extradural haematomas, 19 contusions/haematomas and 3 subarachnoid haemorrhages. 81.5% of the patients had mass lesions potentially requiring surgery. Twenty patients had good functional recovery at 6 months (Glasgow Outcome Score 4 and 5); 18 were dead or vegetative. Age, gender, type of intracranial lesion and presence of coagulopathy were significantly correlated with outcome. Intracranial haematomas continue to be most significant in patients who talk and deteriorate. Coagulopathy was the strongest prognostic predictor of poor outcome with fibrinolytic parameters being reliable prognostic markers of head injury. Early identification, continued monitoring and treatment of coagulopathy should be our new look at improving outcome of these patients.

Battlefield advanced trauma life support.

Prevent secondary injury by: Preventing hypoxia, hypercarbia and hypovolaemia. Giving oxygen if available and ensure a clear airway at all times. Treating fits with diazepam in appropriate doses. Establishing a working diagnosis. Searching for associated injuries. Constantly repeating the mini-neurological examination. Identifying and evacuating appropriate casualties to a neurosurgical unit.

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.

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.