Background The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. Methods From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to “upper good recovery” [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. Results The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). Conclusions At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).
Traumatic brain injury (TBI) has long been recognized as the leading cause of traumatic death and disability. Tremendous advances in surgical and intensive care unit management of the primary injury, including maintaining adequate oxygenation, controlling intracranial pressure, and ensuring proper cerebral perfusion pressure, have resulted in reduced mortality. However, the secondary injury phase of TBI is a prolonged pathogenic process characterized by neuroinflammation, excitatory amino acids, free radicals, and ion imbalance. There are no approved therapies to directly address these underlying processes. Here, we present a case that was intentionally treated with substantial amounts of omega-3 fatty acids (n-3FA) to provide the nutritional foundation for the brain to begin the healing process following severe TBI. Recent animal research supports the use of n-3FA, and clinical experience suggests that benefits may be possible from substantially and aggressively adding n-3FA to optimize the nutritional foundation of severe TBI patients and must be in place if the brain is to be given the opportunity to repair itself to the best possible extent. Administration early in the course of treatment, in the emergency department or sooner, has the potential to improve outcomes from this potentially devastating public health problem.
Single and repeated sports-related mild traumatic brain injury (mTBI), also referred to as concussion, can result in chronic post-concussive syndrome (PCS), neuropsychological and cognitive deficits, or chronic traumatic encephalopathy (CTE). However PCS is often difficult to diagnose using routine clinical, neuroimaging or laboratory evaluations, while CTE currently only can be definitively diagnosed postmortem. We sought to develop an animal model to simulate human repetitive concussive head injury for systematic study. In this study, mice received single or multiple head impacts by a stereotaxic impact device with a custom-made rubber tip-fitted impactor. Dynamic changes in MRI, neurobiochemical markers (Tau hyperphosphorylation and glia activation in brain tissues) and neurobehavioral functions such as anxiety, depression, motor function and cognitive function at various acute/subacute (1-7 day post-injury) and chronic (14-60 days post-injury) time points were examined. To explore the potential biomarkers of rCHI, serum levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau) were also monitored at various time points. Our results show temporal dynamics of MRI consistent with structural perturbation in the acute phase and neurobiochemical changes (P-Tau and GFAP induction) in the subacute and chronic phase as well as development of chronic neurobehavioral changes, which resemble those observed in mTBI patients.
Background In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. Methods We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). Results We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). Conclusions In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414 .).
Our aim was to assess risk of Parkinson disease (PD) following traumatic brain injury (TBI), including specifically mild TBI (mTBI), among care recipients in the Veterans Health Administration.
Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.
Head injuries across all age groups represent an extremely common emergency department (ED) presentation. The main focus of initial assessment and management rightly concentrates on the need to exclude significant pathology, that may or may not require neurosurgical intervention. Relatively little focus, however, is given to the potential for development of post-concussion syndrome (PCS), a constellation of symptoms of varying severity, which may bear little correlation to the nature or magnitude of the precipitating insult. This review aims to clarify the aetiology and terminology surrounding PCS and to examine the mechanisms for diagnosing and treating.
BACKGROUND:: To investigate the efficacy and indications of zolpidem, a nonbenzodiazepine hypnotic, inducing arousal in vegetative state patients after brain injury. METHODS:: One hundred sixty-five patients were divided into 4 groups, according to area of brain damage and injury mechanism. All patients' brains were imaged by Tc-ECD single-photon emission computerized tomography (SPECT), before and 1 hour after treatment with 10 mg of zolpidem. Simultaneously, 3 quantitative indicators of brain function and damage were obtained using cerebral state monitor. Thirty-eight patients withdrew from the study after the first zolpidem dose. The remaining 127 patients received a daily dose of 10 mg of zolpidem for 1 week and were monitored again at the end of this week. RESULTS:: One hour after treatment with zolpidem, cerebral state index was increased and burst suppression reduced in both brain contrecoup contusion and space-occupying brain compression groups (P < 0.05). SPECT showed, 1 hour after medication, that cerebral perfusion was improved in both brain contrecoup contusion and space-occupying brain compression groups, but no changes were seen in primary and secondary brain stem injury groups. In the 127 patients' group, after 1 week of zolpidem treatment, all parameters obtained from cerebral state monitor were not statistically different compared with those after the initial medication (P > 0.05). CONCLUSIONS:: Zolpidem is an effective medicine to restore brain function in patients in vegetative state after brain injury, especially for those whose brain injuries are mainly in non-brain-stem areas. Improvement of brain function is sudden rather than gradual.
: To investigate the potential cumulative impact of mild traumatic brain injury (MTBI) on postconcussive symptoms.
ABSTRACT Traumatic brain injury (TBI) is an important health issue with high prevalence. The most common type of TBI is mild TBI (MTBI). MTBI is known as a condition with self-limited symptoms; however, it could cause some structural abnormalities of brain and become complicated. Visible structural brain damage could have an important effect on recovery after MTBI, but the outcome is not fully understood. This study investigated the clinical course of MTBI patients with the existence of contusion in computed tomography (CT) imaging. Fifty patients with MTBI and simultaneous brain contusion in CT scan were enrolled according to specific exclusion criteria in 14 month. Patients were followed up for two weeks after their first arrival for neurosurgical interventions, decreased level of consciousness, and other neurological complications. Presence of neurological symptoms increased duration of hospital stay and number of CT scans. Forty-two percent of MTBI patients with contusion did not have any objective neurological signs. Fifty percent returned to the hospital with neurologic symptoms and signs. Leading causes were headache followed by seizure and dizziness. Rehospitalization was increased in the patients with altered level of consciousness. The size of brain contusion increased in two patients without further need for neurosurgical intervention. Contusion alone did not worsen the prognosis of patients in short-term follow-up and did not cause neurosurgical interventions.