Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is the first cause of healthcare-associated infections in intensive care units (ICUs) and brain injury is one of the main risk factors for early-onset VAP. Antibiotic prophylaxis has been reported to decrease their occurrence in brain-injured patients, but a lack of controlled randomised trials and the risk of induction of bacterial resistance explain the low level of recommendations. The goal of this study is to determine whether a single dose of ceftriaxone within the 12 hours postintubation after severe brain injury can decrease the risk of early-onset VAP. METHODS AND ANALYSIS: The PROPHY-VAP is a French multicentre, randomised, double-blind, placebo-controlled, clinical trial. Adult brain-injured patients (n=320) with a Glasgow Coma Scale ≤12, requiring mechanical ventilation for more than 48 hours, are randomised to receive either a single dose of ceftriaxone 2 g or a placebo within the 12 hours after tracheal intubation. The primary endpoint is the proportion of patients developing VAP from the 2nd to the 7th day after mechanical ventilation. Secondary endpoints include the proportion of patients developing late VAP (>7 days after tracheal intubation), the number of ventilator-free days, VAP-free days and antibiotic-free days, length of stay in the ICU, proportion of patients with ventilator-associated events and mortality during their ICU stay. ETHICS AND DISSEMINATION: The initial research project was approved by the Institutional Review Board of OUEST III (France) on 20 October 2014 (registration No 2014-001668-36) and carried out according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament relating to the Good Clinical Practice guidelines. The results of this study will be presented in national and international meetings and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02265406; Pre-results.

Urologic dysfunction and neurologic outcome in coma survivors after severe traumatic brain injury in the postacute and chronic phase.

OBJECTIVES: To investigate voiding dysfunction and upper urinary tract status in survivors of coma resulting from traumatic brain injury (TBI), and to compare clinical and urodynamic results with neurologic and psychological features as well as functional outcomes. DESIGN: Observational study focused on urologic dysfunction and neurologic outcome in coma survivors after traumatic brain injury in the postacute and chronic phase. SETTING: A postcoma unit in a rehabilitation hospital. PARTICIPANTS: Consecutive patients (N=57) who recovered from coma of traumatic etiology and who were admitted during a 1-year period to a postcoma unit of a rehabilitation hospital. INTERVENTIONS: Patients underwent clinical urologic assessment, urodynamics with the assessment of the Schafer nomogram and the projected isovolumetric detrusor pressure to evaluate detrusor contractility, ultrasound assessment of the lower and upper urinary tract and voiding cystourethrography, routinely performed, according to the International Continence Society Standards. Neurologic variables assessed were brain injury and disability severity, and neuropsychological status. Neuroimaging identified the site of cerebral lesions. MAIN OUTCOME MEASURES: Urinary symptoms, disability by means of the Glasgow Outcome Scale (GOS), and neuropsychological status by means of the Neurobehavioral Rating Scale (NBRS), and the relationships among them. RESULTS: Of the 57 patients studied, 30 had overactive bladder (urge incontinence) symptoms, 28 had detrusor overactivity, and 18 had detrusor underactivity with associated pseudodyssynergia in 15 of these patients. Eleven patients had hypertrophic bladder; 3, bilateral pyelectasia; and 2, vesicoureteral reflux. Disability measured by GOS was severe in 8 patients and moderate in 27, while recovery was good in 22 patients. The mean NBRS total score indicated a mild cognitive impairment. Neuroimaging showed diffuse brain injury in all patients. Statistically significant relationships were found between urge incontinence, detrusor overactivity, and poor neurologic functional outcome, between detrusor overactivity and right hemisphere damage (P=.0001), and between impaired detrusor contractility and left hemisphere injuries (P=.0001). CONCLUSIONS: Most patients who recovered from coma resulting from TBI have symptoms of overactive bladder syndrome and voiding difficulties. These urinary problems correlate with cerebral involvement and neurologic functional outcome.

Cognitive deficits after traumatic coma.

Survivors from a coma due to severe traumatic brain injury (TBI) frequently suffer from long-lasting disability, which is mainly related to cognitive deficits. Such deficits include slowed information processing, deficits of learning and memory, of attention, of working memory, and of executive functions, associated with behavioral and personality modifications. This review presents a survey of the main neuropsychological studies of patients with remote severe TBI, with special emphasis on recent studies on working memory, divided attention (dual-task processing), and mental fatigue. These studies found that patients have difficulties in dealing with two simultaneous tasks, or with tasks requiring both storage and processing of information, at least if these tasks require some degree of controlled processing (i.e., if they cannot be carried out automatically). However, strategic aspects of attention (such as allocation of attentional resources, task switching) seem to be relatively well preserved. These data suggest that severe TBI is associated with a reduction of resources within the central executive of working memory. Working memory limitations are probably related to impaired (i.e., disorganized and augmented) activation of brain executive networks, due to diffuse axonal injury. These deficits have disabling consequences in everyday life.

Analysis of intracranial pressure changes during early versus late percutaneous tracheostomy in a neuro-intensive care unit.

BACKGROUND: We aimed to investigate intracranial pressure (ICP) changes during early versus late bedside percutaneous tracheostomy (PT) in a neuro-intensive care unit (NICU). METHODS: This study included 30 patients admitted to our NICU for head trauma, subarachnoid haemorrhage, intracerebral haematoma or brain tumour with a Glasgow Coma Score (GCS) less than 8. These patients also underwent ICP monitoring. Bedside PT was performed either early (within 7 days of ventilation) or late (after 7 days of ventilation) via the Griggs system. In all patients; ICP, systemic blood pressure, heart rate, oxygen saturation (Sat O(2)) and arterial blood gases were recorded 5 min before the procedure, during skin incision, during tracheal cannulation, as well as 5 min and 10 min after the procedure. FINDINGS: Thirty patients, 18 male and 12 female, with various intracranial pathologies between ages 18 and 78 (mean 38.7 +/- 20) were identified. The admission GCS ranged between 4 and 11 (median 7). Physiological variables did not differ significantly between the two groups. In the early group, ICP values measured 5 min before the procedure, during skin incision, during tracheal cannulation, as well as 5 min and 10 min after the procedure were 15.1 +/- 5.2, 22 +/- 10.1, 28.4 +/- 13.7, 17.3 +/- 7.1, 13.8 +/- 5.0 mmHg, respectively. In the late group, these values were 14.2 +/- 4.5, 17.2 +/- 5.5, 21.5 +/- 8.0, 15.1 +/- 5.3 and 12.4 +/- 4.1 mmHg. There was no significant difference between the early or late groups in terms of ICP increases during these predetermined 5 time points. CONCLUSIONS: In patients with decreased intracranial compliance, a relatively minimally invasive procedure such as PT may lead to significant increases in ICP. The timing of PT does not seem to influence ICP, mortality, pneumonia or early complications. During the PT procedure, ICP should be closely monitored and preventive strategies should be instituted in an attempt to prevent secondary insult to an already severely injured brain.

Prognosis following severe head injury: Development and validation of a model for prediction of death, disability, and functional recovery.

BACKGROUND: A prognostic model for head trauma patients is useful only if it predicts clinically relevant outcomes accurately on new subjects in various settings. Most existing models consider only dichotomous outcome and have not been tested externally. We developed and validated a rule for prediction of three functional outcome states after severe head injury, using information from day 1. METHODS: The model was developed in a cohort of 304 adults who were admitted to a Dutch trauma center and had survived and remained comatose for >24 hours following severe head injury. We used ordinal logistic regression analysis to predict the extended Glasgow Outcome Scale after > or =12 months, merged into three categories. We preselected five known predictors of outcome and used bootstrapping techniques to avoid statistical overfitting. The performance of the model was subsequently tested in a cohort of 122 patients from an unrelated hospital. RESULTS: The model contained age (p < 0.0001), best motor response on day 1 (p = 0.002), pupil response after resuscitation (p = 0.005), computed tomography findings (p = 0.004), and presence of arterial hypotension (p = 0.37) as predictor variables. In the external validation cohort, the model showed adequate agreement between observed and predicted outcome probabilities (calibration). The model had a good ability to discriminate patients with different outcomes (c-statistic 0.808). The predictive accuracy was 66% when the model was used to classify patients across the three outcome categories. CONCLUSIONS: We have developed a practical model for predicting the probability of death, survival with major disability, and functional recovery in patients who are comatose 24 hours after severe head injury. The model performed well in an external setting, indicating that measures to avoid statistical overfitting were successful.

Gender as a moderator of memory after traumatic brain injury in children.

OBJECTIVE: To explore the possibility that gender has a moderating effect on memory after pediatric traumatic brain injury (TBI). DESIGN: Controlled group study. Gender effects between and within groups were evaluated by means of effect size comparisons and hierarchical regression analysis. SETTING: Regional rehabilitation center. PARTICIPANTS: Seventy children with TBI, selected from a 4-year series of consecutive referrals, and 70 demographically matched controls. MAIN OUTCOME MEASURES: Screening version of the Wide Range Assessment of Memory and Learning (WRAML-S) and the Wechsler Intelligence Scale for Children-Third Edition (WISC-III). RESULTS: Boys with TBI performed worse than girls with TBI, and worse than their counterparts in the control group, on the WRAML-S. There was no gender effect in the control group. Gender explained an additional 9% of the variance in WRAML-S performance over and above injury severity and age variables. However, gender differences were largely attenuated when speed of information processing, as assessed by the WISC-III, was used as a covariate. CONCLUSION: The effect of TBI on children's memory appears to be moderated by gender and may be mediated by speed of information processing.

Rehabilitation outcome in a patient awakened from prolonged coma.

BACKGROUND: This article describes the rehabilitation of a patient recovering from a prolonged coma (defined as lasting longer than 4 weeks). The case is noteworthy because it exemplifies the possibilities and difficulties entailed in treating these patients, who are often regarded as too severely impaired to justify intensive rehabilitation efforts. CASE REPORT: The patient is a 28-year old Polish male, unmarried, who suffered serious closed head injuries in an automobile accident in April of 1999. He was in a comatose state for more than two months, with a GCS score of 5. When admitted for rehabilitation he was bedridden, with global aphasia, agraphia, limb apraxia, and executive dysfunction. The rehabilitation program developed for him is described in detail. RESULTS: Over the course of rehabilitation, which began in December 1999 and continues to this writing, the patient has regained locomotion capabilities (though with impairments), and his speech has improved considerably. The apraxia has largely resolved, and he is able to write his name and copy words. He is now capable of performing many activities of daily living. CONCLUSIONS: A comprehensive program of rehabilitation characterized by a strategic, heuristic approach is capable of achieving a good outcome even in very difficult cases, such as prolonged coma.

Tracheostomy in children: there is a place for acceptable risk.

BACKGROUND: Tracheostomy in children remains controversial regarding the risk of complications. METHODS: Forty-six trauma patients (35 male and 11 female, mean age = 6.8 years) were admitted to the intensive care unit between 1987 and 1991 with severe head injury plus coma. Tracheostomy was performed with standard technique after 5.9 days (range, 2-12 days) of intubation. RESULTS: There were no deaths from tracheostomy, but six deaths resulted from severe head injury. One child was discharged with tracheostomy. The 39 survivors remained with tracheostomy 16.14 days (range, 4-71 days) in the intensive care unit. After cannula removal, 31 remained asymptomatic; 8 had respiratory distress: 2 were normal, 5 had endoscopic treatment for subglottic granulomas/stenosis from intubation, and 1 had tracheomalacia from tracheostomy. In 1997, the 18 patients located for follow-up were asymptomatic. At endoscopy, 8 were normal, 9 had subglottal granulomas from intubation, and 1 had 20% tracheal stenosis from tracheostomy. CONCLUSION: Most complications after tracheostomy result from intubation. Tracheostomy has an acceptable risk in children with severe head injury who need prolonged ventilatory support.

[Head trauma and brain auditory evoked potentials].

The study investigated brain auditory evoked potentials (BAEP) in patients complaining auditory disturbances after head trauma. The results showed that the incidence of hearing loses was 57.5% and the rate of abnormality of BAEP is 33.75%. The types of the abnormalities of BAEP varied and were related with the position and severity of the head trauma. The types of the abnormalities manifested as loses of I-II waves, prolongation of V latency and I-V interlatency.