Clinical Implications of Basic ResearchCurrent concepts: Diffuse axonal injury–associated traumatic brain injury☆,☆☆,★
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Incidence and social cost
There are approximately 500,000 new cases of TBI admitted to hospitals in the United States each year,1, 2, 3 and the incidence requiring hospitalization is estimated to be approximately 200 to 225 per 100,000 population.1, 2 Currently, it is estimated that brain injuries account for 12% of all hospital admissions in the United States.4
Transportation-related injuries of all types are responsible for approximately 50% of TBI within the United States.5, 6, 7 The predominant mechanism in most
Human data
DAI was initially described by a pathologist.16 These findings were noted to occur in patients who died from a severe TBI following a high-speed transportation injury. On histologic examination, the patients were noted to have neuronal anatomic changes of diffuse axonal degeneration. It has been stated that DAI is a misnomer. It is not diffuse throughout the whole brain, but rather it is predominant in discrete regions of the brain following high-speed, long-duration deceleration injuries.
MVCs
Current animal and physical models
It is difficult to correlate the severity of injury in humans with the current models. The GCS,13 the Disability Rating Scale,30 and the length of posttraumatic amnesia31 cannot be used to assess the outcomes of animals subjected to a TBI. Yet despite the number of experimental neurotrauma in vitro models developed to date, there has not been a reliable, cost-effective in vivo model to mimic mild, moderate, and severe DAI seen in humans.32, 33 Stretching of the axon has been used as an in vitro
Morphologic and biochemical changes in DAI
DAI is characterized microscopically by widespread damage to axons in the cerebral hemispheres, the cerebellum, and the brainstem and is a consistent feature of TBI.8, 24, 25 Traumatically induced axonal damage may be triggered first by focal intraaxonal change involving the neurofilament subunits.45 This neurofilament change is due to either direct mechanical failure of the axonal cytoskeleton or the initiation of a biochemical event that causes neurofilament disassembly.
The histologic
Axonal Changes
A characteristic feature of DAI is a prolonged progression of secondary events that may ultimately result in axonotmesis (interruption of the axon of a nerve followed by complete degeneration of the distal segment). The probable sequence of events was recently summarized by Maxwell et al.33 After injury, there is a depolarization followed by a focal loss of axonal transport as a result of disruption of the cellular organelles. One of the consequences of DAI is direct intracellular injury from
Clinical findings
Severe DAI is usually associated with impairment of consciousness, which begins at the moment of injury.8, 24, 39, 47 It is assumed that DAI has occurred whenever there is any loss of consciousness.5 The GCS may more accurately reflect the amount of midbrain and brainstem injury than cortical injury and, thereby, be a more accurate predictor of outcome with regard to DAI than some other measures of TBI, such as the amount of cortical contusion noted on CT scanning.8
Because the diagnosis can be
Relationship to neuropsychologic complications
Although a broad range of cognitive deficits is possible following TBI, deficits in specific areas seem to predominate. Difficulties with encoding and retrieving new information, commonly referred to as memory abilities, are common following TBI and are often accompanied by problems in information processing and executive skills.81, 82, 83 The percentage of individuals with severe TBI displaying impaired performance on neuropsychologic tests reaches a maximum on tests involving rapid mental
Summary
Before therapeutic rehabilitation interventions are considered, there must be considerable forethought given to the existence of DAI. Further research is necessary to delineate the clinical treatments that are most applicable to the patients who have suffered DAI.
Acknowledgements
We appreciate the donation of the pathology and histology slides on human DAI from Cheryl Palmer, MD, in the Department of Pathology, University of Alabama at Birmingham School of Medicine.
References (107)
- et al.
Epidemiologic aspects of brain injury
Neurol Clin
(1996) - et al.
Assessment of outcome in severe brain damage
Lancet
(1975) - et al.
Staining of amyloid precursor protein to study axonal damage in mild head injury
Lancet
(1994) - et al.
Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model
Neuroscience
(1989) Pathobiology of traumatically induced axonal injury in animals and man
Ann Emerg Med
(1993)Eicosanoids, fatty acids and neutrophils: their relevance to the pathophysiology of disease
Prostaglandins Leukot Essent Fatty Acids
(1995)- et al.
Post-traumatic hypopituitarism due to hypothalamic lesion
Am J Med
(1980) - et al.
Difference in neurotransmitter metabolism in frontotemporal-lobe contusion and diffuse cerebral contusion
Lancet
(1977) - et al.
Cognitive impairment following closed head injury
Neurol Clin
(1992) - et al.
Magnetic resonance identified ventricular dilation in traumatic brain injury: comparison of pre- and postinjury scan and postinjury results
Arch Clin Neuropsychol
(1992)
Psychopharmacologic management of traumatic brain injury
Phys Med Rehabil Clin North Am
The descriptive epidemiology of head trauma in the United States
Epidemiology of head injury.
Rehabilitation of traumatic brain injury
The case for comprehensive residency training in traumatic brain injury: a commentary
Am J Phys Med Rehabil
Factors that influence costs and length of stay of persons with traumatic brain injury in acute care and inpatient rehabilitation
J Head Trauma Rehabil
Consensus Conference. Rehabilitation of persons with traumatic brain injury. NIH Consensus Development Panel on Rehabilitation of Persons with Traumatic Brain Injury
JAMA
Epidemiology
The structural bases of coma and recovery: insights from brain injury in humans and experimental animals
Clinicopathologic observations in 100 consecutive patients with fatal head injury admitted to a neurosurgical unit
Ir Med J
Head injuries: costs and consequences
J Head Trauma Rehabil
The financial trauma of head injury
Brain Inj
Management of head injuries
Rehabilitation of the patient with traumatic brain injury
Diffuse degeneration of the cerebral white matter in severe dementia following head injury
J Neurol Neurosurg Psychiatry
Experimental cerebral concussion
Brain
Shaken adult syndrome
Am J Forensic Med Pathol
Nonaccidental head injury in infants—the “shaken-baby syndrome.”
N Engl J Med
Neuropathology of head injury
Principles and practice of neuropathology
Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury
J Neurotrauma
Diffuse brain damage of immediate impact type: its relationship to “primary brain-stem damage” in head injury
Brain
Diffuse axonal injury in head injury: definition, diagnosis and grading
Histopathology
Traumatic brain injury in high school athletes
JAMA
Concussion among Swedish elite ice hockey players
Br J Sports Med
The applied neuropathology of human spinal cord injury
Spinal Cord
A review of the neuropathology of human spinal cord injury with emphasis on special features
J Spinal Cord Med
Disability rating scale for severe head trauma: coma to community
Arch Phys Med Rehabil
Post-traumatic amnesia and Glasgow Coma Scale related to outcome in survivors in a consecutive series of patients with severe closed-head injury
Brain Inj
In vivo models of experimental brain and spinal cord trauma
A mechanistic analysis of nondisruptive axonal injury: a review
J Neurotrauma
Traumatic brain injury in the rat: characterization of a midline fluid-percussion model
Cent Nerv Syst Trauma
Controlled cortical impact: a new experimental brain injury model
J Neurotrauma
Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue
J Cereb Blood Flow Metab
A new model of diffuse brain injury in rats. Part II: morphologic characterization
J Neurosurg
Diffuse axonal injury and traumatic coma in the primate
Ann Neurol
A research applicable small animal model of diffuse axonal injury
J Neurotrauma
On the mechanics of impact neurotrauma: a review and critical synthesis
Biomechanics of closed head injury
Biomechanics in crash injury research
ISA Trans
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Supported in part by the Centers for Disease Control and Prevention–National Center for Injury Prevention and Control, US Department of Health and Human Services (grant no. R49/CCR403641-11) and the National Institute of Disability and Rehabilitation Research, US Department of Education, Traumatic Brain Injury Model Systems (grant no. H133A980010).
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No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated.
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Reprint requests to Jay M. Meythaler, MD, JD, University of Alabama at Birmingham, R157 Spain Rehabilitation Ctr, 619 19th St S, Birmingham, AL 35249-7330, e-mail: [email protected].