To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition on minimally conscious state (MCS) and provide care ...recommendations for patients with prolonged disorders of consciousness (DoC).
Recommendations were based on systematic review evidence, related evidence, care principles, and inferences using a modified Delphi consensus process according to the AAN 2011 process manual, as amended.
Clinicians should identify and treat confounding conditions, optimize arousal, and perform serial standardized assessments to improve diagnostic accuracy in adults and children with prolonged DoC (Level B). Clinicians should counsel families that for adults, MCS (vs vegetative state VS/unresponsive wakefulness syndrome UWS) and traumatic (vs nontraumatic) etiology are associated with more favorable outcomes (Level B). When prognosis is poor, long-term care must be discussed (Level A), acknowledging that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults (Level B); no tests are shown to improve prognostic accuracy in children. Pain always should be assessed and treated (Level B) and evidence supporting treatment approaches discussed (Level B). Clinicians should prescribe amantadine (100-200 mg bid) for adults with traumatic VS/UWS or MCS (4-16 weeks post injury) to hasten functional recovery and reduce disability early in recovery (Level B). Family counseling concerning children should acknowledge that natural history of recovery, prognosis, and treatment are not established (Level B). Recent evidence indicates that the term chronic VS/UWS should replace permanent VS, with duration specified (Level B). Additional recommendations are included.
During the conflicts of the Global War on Terror, which are Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF), there have been over a quarter of a million diagnosed ...cases of traumatic brain injury (TBI). The vast majority are due to explosive blast. Although explosive blast TBI (bTBI) shares many clinical features with closed head TBI (cTBI) and penetrating TBI (pTBI), it has unique features, such as early cerebral edema and prolonged cerebral vasospasm. Evolving work suggests that diffuse axonal injury (DAI) seen following explosive blast exposure is different than DAI from focal impact injury. These unique features support the notion that bTBI is a separate and distinct form of TBI. This review summarizes the current state of knowledge pertaining to bTBI. Areas of discussion are: the physics of explosive blast generation, blast wave interaction with the bony calvarium and brain tissue, gross tissue pathophysiology, regional brain injury, and cellular and molecular mechanisms of explosive blast neurotrauma.
Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the ...highest rates of TBI‐related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI‐related disabilities. The cost of care is very high.
Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.
The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated ...dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.
Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in ...patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the “grand challenge” of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the “curing coma community” to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.
To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the ...literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days.
Articles were classified per the AAN evidence-based classification system. Evidence synthesis occurred through a modified Grading of Recommendations Assessment, Development and Evaluation process. Recommendations were based on evidence, related evidence, care principles, and inferences according to the AAN 2011 process manual, as amended.
No diagnostic assessment procedure had moderate or strong evidence for use. It is possible that a positive EMG response to command, EEG reactivity to sensory stimuli, laser-evoked potentials, and the Perturbational Complexity Index can distinguish MCS from vegetative state/unresponsive wakefulness syndrome (VS/UWS). The natural history of recovery from prolonged VS/UWS is better in traumatic than nontraumatic cases. MCS is generally associated with a better prognosis than VS (conclusions of low to moderate confidence in adult populations), and traumatic injury is generally associated with a better prognosis than nontraumatic injury (conclusions of low to moderate confidence in adult and pediatric populations). Findings concerning other prognostic features are stratified by etiology of injury (traumatic vs nontraumatic) and diagnosis (VS/UWS vs MCS) with low to moderate degrees of confidence. Therapeutic evidence is sparse. Amantadine probably hastens functional recovery in patients with MCS or VS/UWS secondary to severe traumatic brain injury over 4 weeks of treatment. Recommendations are presented separately.
Objective:
From the ongoing military conflicts in Iraq and Afghanistan, an understanding of the neuroepidemiology of traumatic brain injury (TBI) has emerged as requisite for further advancements in ...neurocombat casualty care. This study reports population‐specific incidence data and investigates TBI identification and grading criteria with emphasis on the role of loss of consciousness (LOC) in the diagnostic rubric.
Methods:
This is a cohort study of all consecutive troops acutely injured during combat operations—sustaining body‐wide injuries sufficient to require immediate stateside evacuation—and admitted sequentially to our medical center during a 2‐year period. A prospective exploration of the TBI identification and grading system was performed in a homogeneous population of blast‐injured polytrauma inpatients.
Results:
TBI incidence was 54.3%. Structural neuroimaging abnormalities were identified in 14.0%. Higher Injury Severity Score (ISS) was associated with abnormal neuroimaging, longer length of stay (LOS), and elevated TBI status—primarily based on autobiographical LOC. Mild TBI patients had normal neuroimaging, higher ISS, and comparable LOS to TBI‐negative patients. Patients who reported LOC had a lower incidence of abnormal neuroimaging.
Interpretation:
This study demonstrates that the methodology used to assign the diagnosis of a mild TBI in troops with complex combat‐related injuries is crucial to an accurate accounting. The detection of incipient mild TBI, based on an identification system that utilizes LOC as the principal diagnostic criterion to discern among patients with outcomes of interest, misclassifies patients whose LOC may not reflect actual brain injury. Attempts to identify high‐risk battlefield casualties within the current point‐of‐injury mild TBI case definition, which favors high sensitivity, will be at the expense of specificity. ANN NEUROL 2012;72:673–681
To review the emerging literature on traumatic brain injury (TBI) caused by explosive blast.
Efforts are underway to understand how explosive blast injures brain, what is the clinical presentation ...and how best to manage it. A major way blast injures brain is from detonation pressure waves coupling to a victim's head leading to brain deformation. The effect of other explosion-related elements is unknown. Because scientific insights take time to develop but injuries are occurring now, the military adopts existing civilian standard of care practices developed for similar diseases, such as the Guidelines for the Management of Severe Traumatic Brain Injury developed mainly for closed head TBI. When these do not exist, the military creates them, such as the Veterans Administration and Department of Defense Clinical Practice Guidelines for Concussion/Mild TBI. Another treatment advance is the creation of the first large system-wide approach to diagnosis and clinical management of TBI, which begins at the site of injury and extends through both the military and the Veterans' Administration medical care systems.
Explosive blast TBI is being addressed at all levels - basic research through clinical care. New clinical practice guidelines are being used in a standardized system-wide approach.
Background/Objective
For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in ...patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis.
Methods
We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development.
Results
Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints.
Conclusions
This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.
Paroxysmal sympathetic hyperactivity (PSH) is characterized by episodic, hyperadrenergic alterations in vital signs after traumatic brain injury (TBI). We sought to apply an objective scale to the ...vital sign alterations of PSH in order to determine whether 1 element might be predictive of developing PSH.
We conducted an observational study of consecutive TBI patients (Glasgow Coma Scale score ≤12) and monitored the cohort for clinical evidence of PSH. PSH was defined as a paroxysm of 3 or more of the following characteristics: (1) tachycardia, (2) tachypnea, (3) hypertension, (4) fever, (5) dystonia (rigidity or decerebrate posturing), and (6) diaphoresis, with no other obvious causation (ie, alcohol withdrawal, sepsis).
The Modified Clinical Feature Severity Scale (mCFSS) was applied to each participant once daily for the first 5 days of hospitalization.
Nineteen (11%) of the 167 patients met criteria for PSH. Patients with PSH had a higher 5-day cumulative mCFSS score than those without PSH (median interquartile range = 36 29-42 vs 29 22-35, P = .01). Of the 4 components of the mCFSS, elevated temperature appeared to be most predictive of the development of PSH, especially during the first 24 hours (odds ratio = 1.95; 95% confidence interval, 1.12-3.40).
Early fever after TBI may signal impending autonomic dysfunction.
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