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Cognitive Impairments Following Traumatic Brain Injury
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Neurotrauma
Cognitive Impairments Following Traumatic Brain Injury Etiologies and Interventions Alice E. Davis, PhD, RN, CNRN, CNP
Traumatic brain injury (TEI) has been identified as a major health problem in this country with an estimated 1.5 to 2 million injuries occurring each year. 33 Survival for those with severe TEI can be attributed to advances in emergency services and to the early and focused management of primary and secondary injuries. Up to 90,000 persons who sustain a TEI experience long-term functional impairments, including physical, cognitive, behavioral, and emotional changes. These functional impairments have far-reaching consequences, including changes in life course, family relationships, social interactions, and financial stability. Whereas physical impairments are problematic, it is the cognitive, emotional, and behavioral sequelae that are most pervasive and disruptive to the lives of patients with TBI and their families. Of the myriad of deficits, it is the loss of cognitive function-including memory and learning, attention and concentration, and executive function-that precludes many of these TEI survivors from participating in the mainstream activities of normal life. 33
From the School of Nursing, University of Michigan, Ann Arbor, Michigan
Although behavioral and emotional problems are often embedded in cognitive dysfunction following TEI, the purpose of this article is to provide substantive knowledge related to the cognitive impairments, namely, changes in awareness, attention, memory, learning, and executive function, that are the hallmarks of TEI. After identifying the anatomic structures and physiologic mechanisms responsible for information processing resulting in cognition, the pathobiology of brain injury and its relationship to cognitive dysfunction are addressed. Finally, an evidencebased approach to interventions that could prevent further cognitive damage and enhance brain recovery, thereby improving cognitive outcomes, is discussed. In so doing, critical care nurses will be better equipped to influence functional outcomes during the immediate critical care phase as well as those outcomes necessa1y for long-term recove1y.
Anatomic and Physiologic Components of Information Processing The central nervous system (CNS) supports the work of sensing and responding to internal or external environmental changes. De-
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spite the complexity of information processing and behavioral responses that need to occur, the structure of the CNS is simple and consists of nerve cells and their connections. Information received by the CNS is sent to primary sensory and association areas of the cortex where processing of individual stimuli takes place. The result of activation of this sophisticated neuronal network is the ability to think and communicate. Cognition is a person's ability to process information in a meaningful way and encompasses the ability to remember, learn, and make decisions. Components of cognition necessary for everyday life are attention and concentration, learning and memory, and executive function. Each of these components of cognition arises from different areas of the brain but are connected in such a way that life experiences are recorded, learning takes place, information is retrieved, and behavioral responses occur. The ability to respond to novel or innovative events experienced in day-to-day life is a result of plasticity. Plasticity is defined as the adaptive capacity of the central nervous system, the brain's ability to modify its organization and function, 2 which allows enduring functional change to take place. Plasticity is a normal process of postnatal growth and development and occurs continuously throughout life. Without plasticity, the brain would not be capable of learning and remembering new information because these activities require existing neuronal pathways to modify and change themselves. Plasticity occurs as a result of neurochemical, receptor, and structural changes within the brain, and evidence of plasticity is expressed in morphologic, physiologic, and behavioral terms. 23 · 46 Morphologic changes are tied most closely with growth and development. Evidence for these plastic changes, documented primarily in animal studies, is based on dendritic sprouting, increased dendritic aborization (i.e., prolific branching of dendrites), and synaptogenesis (i.e., making new synaptic connections). Jones and Schallert21 describe contralateral plastic changes of the dendrites and behavioral recovery of forelimb use following lesions of the sensorimotor strip in rats but also noted pruning of the new dendritic growth once the motor function improved. The presence of pruning suggests that plasticity is limited to the growth neces-
sary to reestablishing function. Physiologic plasticity has long been associated with longterm potentiation (LTP). LTP is the ability of the neuronal cell to remember after it has been electrically stimulated. LTP studies, often associated with learning and memory, have demonstrated that evidence of memory can be detected from days to weeks after the cell has been stimulated. 38 Lastly, behavioral plasticity, much like the morphologic changes seen during growth and development, occurs as a result of experience. Across the lifespan, experience provides a rich reservoir of events that stimulate the brain to grow in new directions, thereby establishing new pathways.
Leaming and Memory Many memory systems, each providing their own unique contribution to information processing, have been identified. Consequently, memory has been broadly classified as explicit and implicit and further delineated with respect to time as a recent, remote, or working memory. Also known as declarative memory, explicit memo1y encodes factual information and life events. Comparisons, evaluations, and references are essential processes in the formation of declarative memories. 12 The highly investigated hippocampal system has been recognized as the primary area for explicit memory since the early 1950s. The hippocampal system, located in the medial temporal lobe, consists of the hippocampus proper, perirhinal structures, and the amygdala. The hippocampal memory system allows for conscious recollection and remembering of specific facts and events 11 • 45 · 45 · so. 51 as well as the encoding of new memories. Spatial representations are also made in the hippocampal system. It is through the use of spatial maps that navigation of the environment is possible. Storage of memories is less clear; it is thought that memories are stored in the hippocampal system for approximately 2 years and then are transferred to other areas of the cortex after that time. How these memories are stored and where they are stored remains unclear; however, this time-dependent aspect of memory allows for retrieval of memories without involving the hippocampal system. Memory systems outside of the hippocampal complex are responsible for implicit mem-
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ory. AJso known as JTH:mory, immemory has an and does not depend on complex conscious recall, or awareness. Procedural memories include reflexes, associations through conditioning, motor skills, or other learned procedures. 12. 01 Activation of a procedural memory such as riding a bicycle is thought to be through cerebellar and basal ganglia systems. Learning is a component of directed attention, memory storage, and memory retrieval. It is not difficult to link learning to the hippocampal system in view of its many roles in making, storing, and retrieving information. For one to learn, information needs not only to be encoded and stored as facts, events, and conditions but to be able to be retrieved for use at specific times. Without storage and retrieval mechanisms, a person is unable to repeat activities even if the skills were practiced. There is a parallel process to learning that allows a person to learn or repeat tasks for an intermediate amount of time without encoding the information for future use. This working memory allows one to briefly remember a dictated phone number or a new psychomotor skill. After completing the task, there is no retrieval of the information because an implicit or explicit memory of the event was not made. Working memory is much like the desktop of a computer; it is temporary storage of information. If it is not saved, the memory is not enduring and learning has not occurred. Executive function implies the coordination and integration of many cognitive processes. Consequently, problem solving, abstract thinking, insight, judgment, information processing, and organization, which have traditionally been defined as executive function, require not a single brain location but several structures and neuronal networks to function adequately. Brain structures and circuits that are highly associated with executive function include the prefrontal cortex, sensory cortices (vision, auditory, and thalamus, and limbic and cortex. It seems, however, that the prefrontal cortex directs the multitude of activities that demand innovative responses in a changing environment.' Whereas cognitive functions such as memo1y, learning, and executive function
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essential for information processocrur becwse arousal and attention mechanisms are intact. Limbic structures, such as the system housed within the brain stem, the ;irousal and attention mechanisms needed to acquire new information, learn the information, and store it as a new memory. Attention, a basic cognitive function, is essential for memory and learning.1 Selective attention is necessa1y for recognizing and stimuli, provides basic arousal function, and serves as the prerequisite for sustained attention or concentration. Sustained attention, necessary to maintain focus despite competing stimuli and thought to be necessary for learning, is measured by registration of the information or immediate recall. Sustained attention occurs as a result of interactions among several brain structures, including the parietal, frontal, medial temporal, subcortical, and reticular areas. 1 This delicate yet sophisticated network of neurons can be disrupted when the brain is injured.
Brain injmy occurs as a result of mechanical forces to the head; the nature, severity, site, and direction of these forces determine the magnitude of injmy. JO The brain injuries resulting from mechanical forces have long been described as primary injuries of either focal or diffuse lesion etiology. 12 The classification system devised by Gennarelli et al ir, provides insight into the pathophysiologic dynamics occurring in brain injmy and provides mutually exclusive lesion definitions for brain injuries. Focal lesions are those brain injuries that can be identified on CT scan as spaceoccupying lesions. They cause mass effect and are thought to be the cause of coma. ·Focal lesions arc defined as extraclural (epidural) hematomas and acute subdural hematomas requiring surgical intervention or other focal which may or may not have required surgery but included some component of space-occupying pathoiogy. Another type of diffuse brain lesion, is classified strictly by coma duration. Subgroups of coma duration are determined by length of coma, that coma less than 24 hours or greater than 24 hours. Those in coma from greater than 24 hours were further identified as having either
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a decerebrate or nondecerebrate component. The classification system devised by Gennarelli et al1 6 remains relevant today and provides the foundation of understanding for the primary injury caused by mechanical forces. The complexity of brain injury, however, continues to unfold as more is learned of the delayed or nonmechanical injuries. Delayed or secondary brain damage, although initiated at the time of mechanical force, is not present clinically for hours to days after injury. Secondary injuries include brain swelling (edema), alterations in the brain's endogenous neurochemical mechanisms, and ischemia. Best known to clinicians are the cerebral dynamic effects of brain injury. These include the changes in volume and pressure associated with swelling, the development of increased intracranial pressure, the shifting of cerebral spinal fluid into the intrathecal spaces, and the dependence of the brain on systemic blood pressure to maintain cerebral perfusion pressure when autoregulation is lost. Adverse changes are immediately apparent by intracranial pressure and jugular venous monitoring, calculation of cerebral perfusion pressure, and mass shifts on CT scans. Less well known or understood are the endogenous neurochemical processes that are initiated as a result of the mechanical distortion. Following injury, a cascade of events occurs that requires hours to days to complete.15 Four mechanisms have been described in the pathobiology of injury, which result in cell dysfunction and delayed cell death: receptor dysfunction, free-radical effects, inflammatory events, and calciummediated damage. 15 Two distinct physiologic injuries, those that directly damage the axon of the neuron (deafferentation) and those that cause widespread neuroexcitation, result from these injury mechanisms. For each of these injury types, specific pathophysiologic characteristics have been described and physiologic dysfunctions have been identified. Axonal injury or deafferentation injury occurs as a result of neurofilament disassembly, which leads to cytoskeletal change, impaired axonal transport, axonal swelling, and disconnection. 36· ·~ 7 Deafferentation occurs as a result of axonal disconnection (axons physically disconnect from one another) and interrupts established neuronal pathways. Neuronal dis-
connection can be diffuse, that is, scattered throughout injured tissue, or concentrated in a focused area of tissue.37 Deafferentation occurs throughout cortex and brain stem and the diffuse or focused pattern of disconnection influences rate and extent of recovery. Neuroexcitation (diffuse) injury, the second type of injury identified in TBI, has been hypothesized by Hayes et al1 7 to be a result of aberrant neuronal information flow and has been described more fully as a neuroexcitatory cascade. Activated by TBI, a neurotransmitter surge occurs as a result of depolarization and nonspecific release of neurotransmitters. In addition, there is an influx into the brain of blood-borne neurotransmitters through the damaged blood-brain barrier. When depolarization occurs, massive amounts of excitatory neurotransmitters, such as glutamate, aspartate, and acetylcholine, are released. 13· 17• 25 - 27 Depolarization is thought to occur as a result of increases in extracellular potassium brought about by mechanical deformation of potassium channels and breakdown of plasma membranes shifting potassium out of the cell. 17 In addition, calciummediated events occur, driving large amounts of calcium into the cell and causing breakdown of cell membranes and the development of free fatty acids. 15 Interestingly, this physiologic cascade of events can be initiated by injury or ischemia. Characterized as a secondary injury, the destructive power of ischemia is widespread and well documented. 5 Although often associated with raised intracranial pressure, episodes of hypoxia, and hypotension, ischemia can also occur alone. Considerable investigation has occurred over the years to determine how the ischemic process evolves. One hypothesis postulates that there is a reduction in regional cerebral blood flow during the first 6 hours after injury even in patients without surgical mass lesions. Persisting for the first 24 hours after injury, this low flow state has been associated with low Glasgow Coma Scores (GCS) and is thought to have detrimental effects on brain cell viability and neurologic recovery. A second hypothesis counters the first, suggesting ischemia is caused not by some single inherent hypoperfusion mechanism but that it occurs as the injury sequelae evolve. Brain shifts that occur with tissue swelling and increased ICP distort and stretch cerebral ves-
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sels and a hypoperfusion state. Changes in the cerebral microvasculature, vasospasm, and hypotension related to other injuries also contribute to development of ischemia. 10 Although ischemia following TEI occurs throughout the brain, the hippocampus located in the medial temporal lobe is most vulnerable to even small changes in perfusion.
Cognitive Dysfuncticn and Brain Injury Cognitive impairments following severe brain injmy are pervasive and span a range of severity from coma to forgetfulness. Cognitive dysfunction following brain injury is not similar in all patients owing to the vast numbers of possible patterns of focal and diffuse prima1y injuries and secondary injuries. Brain damage to specific areas results in an inability to interpret the signal, whereas destruction of the network results in an inability of intact brain structures to receive and interpret signals. Despite the heterogeneity of brain injmy, there are salient features of cognitive dysfunction that may occur in many patients. These features include antegrade amnesia, impaired explicit memory, attention deficit, and alterations in executive function. 24 The complex relationship between cognitive dysfunction and brain injmy is slowly emerging through multiple avenues, including psychologic and neuropsychologic testing, CT scanning, MR imaging, functional MR imaging, PET scanning, and autopsy results. Thus, it is possible to match the pathophysiologic data with the type of cognitive impairment that has been identified. Brain structures and neuronal networks associated with cognitive function seem especially vulnerable to both primary and secondary injury. An understanding of the etiology of the symptoms allows for the development of strategies that may contribute to preventing further injury or to enhancing cognitive recove1y or both. As a result of prima1y injuries, there is direct damage to brain structures. Contusions of the brain are common and are found ve1y frequently in the cortex, especially in the frontal cortex and poles of the temporal cortex. A large percentage of diffuse axonal injuries also occur in the frontal and temporal areas. In fact, the early work of Ommaya and Gen-
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narelli 35 identified the hippocampal mesocortex and temporal neocortex as being substantially injured following trauma to the head. Brain stem injmy, which is associated with rotational forces, and diffuse axonal injury are common and result in damage to the reticularactivating system. The secondary injuries that occur from swelling compromise blood supply to all cortical structures. The temporal lobe and hippocampal system structures are especially vulnerable to swelling because they are often compressed against the tentorium even if uncal herniation does not occur. Additional insult occurs to the hippocampus if hypotension, hypoxia, or hypoxemic episodes take place. These events, even if mild, easily damage the hippocampus, which is the brain structure most vulnerable to ischemia. The brain structures identified as most frequently injured are those responsible in some way for many of the cognitive functions necessary for participating in routine daily activities. One of the most striking and incapacitating cognitive impairments is the loss of recent memory. Known as antegrade amnesia, this enduring loss of declarative or explicit memory is characterized by an inability to remember recent events. Highly associated with injmy to the hippocampal system, patients with these injuries have lost the ability to encode or store information. Ability to make spatial representation and the ability to learn are also impaired. Attentional deficits have also been identified and are most likely the result of direct brain stem injury or injury to networks linking the brain stem with the prefrontal area. One impairment of attention has been described as an inability to adequately focus (selective or "phasic" attention) and another is an inability to sustain attention or concentrate. As a result of attentional deficits, TEI patients have difficulty reading, following conversations, watching a television program, or even maintaining a train of thought. 1 Severe damage to the brain stem and its connecting networks results in prolonged coma. Loss of executive functioning is quite devastating following brain injury. Without executive function, planning and organization are impaired, decision making is difficult, and judgment is compromised. Because of the complexity of this cognitive system, the prefrontal cortex or any number of its connecting
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structures or networks could be damaged and result in executive dysfunction. Although these cognitive impairments are described separately, the reality for a patient with TBI is that multiple problems need to be addressed to regain a meaningful lifestyle.
Research-Based Interventions for Cognitive Impairments Survival for patients with cognitive impairments can be attributed to the early and focused management of primary and secondary injuries. Management plans for persons with TBI must account for the ongoing process of brain damage caused by the delayed effects of injury. By allowing the focal point of therapy to target ongoing change, sequential therapies based on the evolution of the injury can be mounted. 28 • 46 An interesting duality occurs following brain injury, that is, injury mechanisms and recovery mechanisms are activated simultaneously. Unfortunately, there are no interventions to enhance cognitive function directly. Two mechanisms, however, have been identified, neuroprotection and neuroplasticity, that once activated have the potential to reduce neuronal damage or enhance neuronal growth, thereby indirectly improving cognitive function.
Neuroprotectkm Strategies The aim of neuroprotective strategies is to shield the injured brain from the delayed or secondary damage following the brain insult. Interventions that may be effective in protecting neurons from secondary injury target include (1) management of ICP and cerebral perfusion pressure (CPP) through traditional venues including medical management and positioning and (2) disruption of the neurochemical mechanisms activated by the injury cascade. The importance of delayed or secondary injury is being increasingly recognized. Recently published guidelines for the management of severe TBI, which are based on extensive reviews of the research literature, target ff·•w''"~·" cerebral blood flow to prevent ischemia. Hyperventilation (Paco 2 :::::35 mm Hg) in the acute management of brain injury is no longer advocated during the first 24
hours after injury because it causes cerebral vasoconstriction. Hyperventilation is recommended as an option of care only if neurologic deterioration occurs or if ICP is refractory to traditional treatments such as sedation, paralysis, drainage of cerebrospinal fluid (CSP), and osmotic diuresis. 7 CPP has also been targeted by the Brain Trauma Foundation. 6 The critical threshold for CPP has been set between 70 and 80 mm Hg. Although there is not sufficient empirical support for a standard of care related to maintaining CPP above 70 mm Hg, the morbidity and mortality data associate better outcomes with higher CPP. Along with these new recommendations, there is continued support for more traditional approaches to TBI management, including optimizing systemic blood pressure with vasoactive agents, maintaining euvolemia, utilizing sedation and paralyzing agents to manage metabolic demand (e.g., agitation, restlessness), and aggressive treatment of ICP elevations. 8 Another powerful intervention that can be used effectively to prevent secondary injury is patient positioning. Since the classic study by Mitchell and Mauss, 32 nurse researchers and others have investigated the effect of positioning on ICP and CPP. Reporting results of an integrated review on positioning research indicate routine standards of care are not recommended for positioning of patients with TBI. 20 Rather, the literature supports patient positioning, especially head-of-bed elevation and turning, that optimizes CPP and minimizes ICP. 20 Reduction in core body temperature has also been examined as a neuroprotective method. A preliminary trial using moderate hypothermia (i.e., temperatures of 33°C) has demonstrated a reduction in mortality and improved short-term psychologic function after brain trauma. The use of hypothermia as a neuroprotective strategy is based on the theory that the secondary injury cascade can be attenuated by lowering metabolism, which in turn reduces the posttraumatic neurochemical response. 29 It is important to note that core temperature reduction using moderate hypothermia requires a strict protocol for implementation and should not be confused with routi:r:e use of for 1f-'rnnP"'" reduction. The neurochemical cascade that follows TBI is well documented, and the pharmaco-
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logic manipulation of the associated signs and symptoms is under intense investigation. Future treatment of brain injury will undoubtedly include administering combinations of neuroprotective agents, but most likely they will be given within designated windows with an emphasis on sequence and concurrent administration. The following agents have been or are currently under investigation: anticholinergics or cholinomimetics, anti-inflammatory agents, calcium channel blockers, cal pain antagonists, free-radical scavengers, and glutamate antagonists. 29 In addition, treatments to diminish the acidosis generated by anaerobic metabolism are also being examined. 34 The hypothesized mechanisms of action of these agents are complex and beyond the scope of this article, and readers are encouraged to read the cited references. The pathobiology of TBI is complex, and the role of neuroprotective intervention spans a wide continuum. Developing successful neuroprotective strategies will occur only with continued focus on the acute and chronic sequence of events, windows of opportunity, delivery strategies, and the potential use of combinations of therapies. In the future, more innovative clinical trials will be conducted using neuroprotective agents. 29
Neuroplasticity Although slow and incomplete, cognitive and motor recovery following diffuse and axonal injury is possible. Recovery of function is thought to occur as a result of resolution of local factors such as edema but more importantly through plasticity. Plasticity has also been described as a consequence of deafferentation injury where remaining axons sprout and grow new connections. 32 Several mechanisms are thought to enhance plasticity, including the release of neurotrophic factors and environmental enrichment. Following injury, the peptide neurotrophic or growth factors are expressed. These factors induce sprouting of neurites (neuronal plasticity) and facilitate guidance of neurons to their proper targets. Nerve growth factor, basic fibroblast growth factor, brain-derived nerve growth factor, and neurotrophin-3 are just a few of the many factors identified. There is evidence that neurotrophic factors are altered following brain injury, perhaps in an
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effort to facilitate repair and reestablish functional connections. 29· 47 More recent evidence expands the role of neurotrophic factors to include damage prevention and promotion of regenerative processes after brain injury. Consequently, the integrity of neurons as well as the structure and function of neurons is preserved and long-term damage is attenuated. 28 Much of the pioneering work related to the effect of neurotrophic factors has been gleaned from animal studies. Prevention of cell death in neurons projecting to hippocampus18· 49 following ischemic and neuroexcitatory lesions 14• 40 and decreases in cognitive dysfunction associated with septal lesions 41 • 42 have been reported following administration of nerve growth factor. McDermott et al28 reported improvement in cognitive function in rats that received continuous basic fibroblast growth factor (bFGF) for 7 days following brain injury. From the research comes the notion that neurotrophic factors may have a delayed or prolonged therapeutic window, enabling administration of these types of agents beyond the critical phase of injury. Clinical use for the administration of neurotrophic factors remains under investigation. Because it seems that expression of neurotrophic factors is an advantage to recovery, treatments that may minimize or diminish their effectiveness should be scrutinized. Prophylactic use of anticonvulsants has become commonplace in the treatment of brain injury because of the untoward effects of seizures, namely, increased metabolic demand and release of excitatory neurotransmitters; however, the indiscriminate use of anticonvulsants is not without risk Schierhout and Roberts 39 systematically reviewed randomized controlled trials to examine the effectiveness and safety of antiepileptic agents in the treatment of acute TBI. Results of their review suggest that antiepileptic agents may actually delay neurologic recovery and contribute to impaired cognition and motor function. Moreover, there was no evidence that prophylactic use of antiepileptics used at any time after head injury reduced death and disability. As a result of their review, antiepileptics were recommended only in high-risk patients and during the first week after injury. Environmental manipulation has been shown to influence cognitive function and to produce long-lasting changes in neuronal
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structure. 3 Through experience-dependent mechanisms, new synapses are generated in response to experiences, and opportunities for learning can occur. Consequently, sensory stimulation paradigms using novel and meaningful stimuli have been used in an attempt to increase arousal in patients who are comatose.9· 22 • 31 Although there have been positive responses by patients to sensory stimulation programs, it is difficult to determine if positive recovery trajectories are the effect of normal brain healing or increased plasticity. Unfortunately, this question is not resolved easily in clinical studies. Useful clinical information coming from sensory stimulation research suggests it is a safe intervention even early after injury. 9 The efficacy of sensory stimulation programs for persons in coma following TBI has yet to be determined, but there is still the need to create environments that promote plasticity. It is the rich experiences of everyday life that have demonstrated positive effects on cognition after brain injury. 23 •46 Efforts should be made to use meaningful conversa-
tion, orientation techniques, arousal methods such as bells and blocks, familiar voices, and music in an attempt to promote novel environments for the healing brain. 10• 19 As patients are able to actively participate in the rehabilitation process and participate in neuropsychologic testing, the complex overlap of cognitive impairments may be better understood. The rehabilitation approach is often difficult given the multitude of impairments; however, some strategies have been useful. For memory impairments, supporting techniques and aids such as notebooks and computers are more beneficial than repetitive memory exercises. Unfortunately, researchbased strategies for managing impairments in executive dysfunction are minimal. Access to care, system services, and financial resources become priorities when planning discharge from an acute care setting. Such services should emphasize the important interaction between individuals and their environments, as this is necessary in determining real-world successes and failures. 48
SUMM.AR'ti' Brain injury is a dynamic process that continues for weeks. Recovery is also a lengthy process, proceeding in overlapping stages along with injury. The outcome for many patients with TBI is an inability to fully participate in life events because of.cognitive impairments. Physiologic responses throughout the injury an,d recovery are punctuated by neuroprotective and neuroplastic events. The time course of these injury and recovery activities requires that medical and nursing therapies. are targeted across the trajectory of injury as damage and recovery processes are occurring. Prevention of secondary injury using medical and nursing strategies should be of paramount importance. Altering the environment by .providing meaningful yet novel sensory stimulation may enhance plasticity .and lead. to reorganization of structures that support cognitive processes. Administration of neuroprotective agents in an effort to control damage from neurochemieal processes should proceed as these agents become approved fordinical use, Active participation in rehabilitation programs and rteu...... ropsychologic.testingprovide.additionala.ve:nuesfor.identifying.andaddressing. cognitive impairments. the complex relationship between injury and cognitive impairment is slowly being unraveled. Through an understanding of the brain structures and networks associated with information processing as well as the pathophysiologic consequences of brain injury, critical care nurses can design evidence-based regimens of care that preserve cognitive function and result in improvement of long-term cognitive outcomes and fuller participation in everyday life activities.
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570, 1991 41. Sinson G, Voddi M, Mcintosh T: Nerve growth factor administration attenuates cognitive but not neurobehavioral motor dysfunction or hippocampal cell loss following fluid-percussion injury in rats. J Neurochem 65:2209-2216, 1995 42. Sinson G, Voddi M, Mcintosh T: Combined fetal neural transplantation and nerve growth factor infusion: Effects on neurological outcome following tluidpercussion brain injury in the rat.] Neurosurg 84:655-
662, 1996
100:203-210, 1994 47. Stephenson R: A review of plasticity: Some implications for physiotherapy in the treatment of lesions of the brain. Physiotherapy 79:699-704, 1993 48. Whyte J: Rehabilitation of individuals with traumatic brain injury: Status of the art and science. Report of the NIH Consensus Development Conference on the Rehabilitation of Persons with Traumatic Brain Injury, pp 39-45. Bethesda, MD, National Institutes of Health, 1999 49. Williams L, Varon S, Peterson G, et al: Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Nat Acad Sci 83:9231-9235, 1986 50. Zola-Morgan S, Squire L: The primate hippocampal formation: Evidence for a time-limited role in memory storage. Science 250:288-290, 1990
Address reprint requests to Alice E. Davis, PhD, RN, CNRN, CNP School of Nursing University of Michigan 400 North Ingalls Ann Arbor, MI 48109
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Neurotrauma
Cognitive Impairments Following Traumatic Brain Injury Etiologies and Interventions Alice E. Davis, PhD, RN, CNRN, CNP
Traumatic brain injury (TEI) has been identified as a major health problem in this country with an estimated 1.5 to 2 million injuries occurring each year. 33 Survival for those with severe TEI can be attributed to advances in emergency services and to the early and focused management of primary and secondary injuries. Up to 90,000 persons who sustain a TEI experience long-term functional impairments, including physical, cognitive, behavioral, and emotional changes. These functional impairments have far-reaching consequences, including changes in life course, family relationships, social interactions, and financial stability. Whereas physical impairments are problematic, it is the cognitive, emotional, and behavioral sequelae that are most pervasive and disruptive to the lives of patients with TBI and their families. Of the myriad of deficits, it is the loss of cognitive function-including memory and learning, attention and concentration, and executive function-that precludes many of these TEI survivors from participating in the mainstream activities of normal life. 33
From the School of Nursing, University of Michigan, Ann Arbor, Michigan
Although behavioral and emotional problems are often embedded in cognitive dysfunction following TEI, the purpose of this article is to provide substantive knowledge related to the cognitive impairments, namely, changes in awareness, attention, memory, learning, and executive function, that are the hallmarks of TEI. After identifying the anatomic structures and physiologic mechanisms responsible for information processing resulting in cognition, the pathobiology of brain injury and its relationship to cognitive dysfunction are addressed. Finally, an evidencebased approach to interventions that could prevent further cognitive damage and enhance brain recovery, thereby improving cognitive outcomes, is discussed. In so doing, critical care nurses will be better equipped to influence functional outcomes during the immediate critical care phase as well as those outcomes necessa1y for long-term recove1y.
Anatomic and Physiologic Components of Information Processing The central nervous system (CNS) supports the work of sensing and responding to internal or external environmental changes. De-
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spite the complexity of information processing and behavioral responses that need to occur, the structure of the CNS is simple and consists of nerve cells and their connections. Information received by the CNS is sent to primary sensory and association areas of the cortex where processing of individual stimuli takes place. The result of activation of this sophisticated neuronal network is the ability to think and communicate. Cognition is a person's ability to process information in a meaningful way and encompasses the ability to remember, learn, and make decisions. Components of cognition necessary for everyday life are attention and concentration, learning and memory, and executive function. Each of these components of cognition arises from different areas of the brain but are connected in such a way that life experiences are recorded, learning takes place, information is retrieved, and behavioral responses occur. The ability to respond to novel or innovative events experienced in day-to-day life is a result of plasticity. Plasticity is defined as the adaptive capacity of the central nervous system, the brain's ability to modify its organization and function, 2 which allows enduring functional change to take place. Plasticity is a normal process of postnatal growth and development and occurs continuously throughout life. Without plasticity, the brain would not be capable of learning and remembering new information because these activities require existing neuronal pathways to modify and change themselves. Plasticity occurs as a result of neurochemical, receptor, and structural changes within the brain, and evidence of plasticity is expressed in morphologic, physiologic, and behavioral terms. 23 · 46 Morphologic changes are tied most closely with growth and development. Evidence for these plastic changes, documented primarily in animal studies, is based on dendritic sprouting, increased dendritic aborization (i.e., prolific branching of dendrites), and synaptogenesis (i.e., making new synaptic connections). Jones and Schallert21 describe contralateral plastic changes of the dendrites and behavioral recovery of forelimb use following lesions of the sensorimotor strip in rats but also noted pruning of the new dendritic growth once the motor function improved. The presence of pruning suggests that plasticity is limited to the growth neces-
sary to reestablishing function. Physiologic plasticity has long been associated with longterm potentiation (LTP). LTP is the ability of the neuronal cell to remember after it has been electrically stimulated. LTP studies, often associated with learning and memory, have demonstrated that evidence of memory can be detected from days to weeks after the cell has been stimulated. 38 Lastly, behavioral plasticity, much like the morphologic changes seen during growth and development, occurs as a result of experience. Across the lifespan, experience provides a rich reservoir of events that stimulate the brain to grow in new directions, thereby establishing new pathways.
Leaming and Memory Many memory systems, each providing their own unique contribution to information processing, have been identified. Consequently, memory has been broadly classified as explicit and implicit and further delineated with respect to time as a recent, remote, or working memory. Also known as declarative memory, explicit memo1y encodes factual information and life events. Comparisons, evaluations, and references are essential processes in the formation of declarative memories. 12 The highly investigated hippocampal system has been recognized as the primary area for explicit memory since the early 1950s. The hippocampal system, located in the medial temporal lobe, consists of the hippocampus proper, perirhinal structures, and the amygdala. The hippocampal memory system allows for conscious recollection and remembering of specific facts and events 11 • 45 · 45 · so. 51 as well as the encoding of new memories. Spatial representations are also made in the hippocampal system. It is through the use of spatial maps that navigation of the environment is possible. Storage of memories is less clear; it is thought that memories are stored in the hippocampal system for approximately 2 years and then are transferred to other areas of the cortex after that time. How these memories are stored and where they are stored remains unclear; however, this time-dependent aspect of memory allows for retrieval of memories without involving the hippocampal system. Memory systems outside of the hippocampal complex are responsible for implicit mem-
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ory. AJso known as JTH:mory, immemory has an and does not depend on complex conscious recall, or awareness. Procedural memories include reflexes, associations through conditioning, motor skills, or other learned procedures. 12. 01 Activation of a procedural memory such as riding a bicycle is thought to be through cerebellar and basal ganglia systems. Learning is a component of directed attention, memory storage, and memory retrieval. It is not difficult to link learning to the hippocampal system in view of its many roles in making, storing, and retrieving information. For one to learn, information needs not only to be encoded and stored as facts, events, and conditions but to be able to be retrieved for use at specific times. Without storage and retrieval mechanisms, a person is unable to repeat activities even if the skills were practiced. There is a parallel process to learning that allows a person to learn or repeat tasks for an intermediate amount of time without encoding the information for future use. This working memory allows one to briefly remember a dictated phone number or a new psychomotor skill. After completing the task, there is no retrieval of the information because an implicit or explicit memory of the event was not made. Working memory is much like the desktop of a computer; it is temporary storage of information. If it is not saved, the memory is not enduring and learning has not occurred. Executive function implies the coordination and integration of many cognitive processes. Consequently, problem solving, abstract thinking, insight, judgment, information processing, and organization, which have traditionally been defined as executive function, require not a single brain location but several structures and neuronal networks to function adequately. Brain structures and circuits that are highly associated with executive function include the prefrontal cortex, sensory cortices (vision, auditory, and thalamus, and limbic and cortex. It seems, however, that the prefrontal cortex directs the multitude of activities that demand innovative responses in a changing environment.' Whereas cognitive functions such as memo1y, learning, and executive function
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essential for information processocrur becwse arousal and attention mechanisms are intact. Limbic structures, such as the system housed within the brain stem, the ;irousal and attention mechanisms needed to acquire new information, learn the information, and store it as a new memory. Attention, a basic cognitive function, is essential for memory and learning.1 Selective attention is necessa1y for recognizing and stimuli, provides basic arousal function, and serves as the prerequisite for sustained attention or concentration. Sustained attention, necessary to maintain focus despite competing stimuli and thought to be necessary for learning, is measured by registration of the information or immediate recall. Sustained attention occurs as a result of interactions among several brain structures, including the parietal, frontal, medial temporal, subcortical, and reticular areas. 1 This delicate yet sophisticated network of neurons can be disrupted when the brain is injured.
Brain injmy occurs as a result of mechanical forces to the head; the nature, severity, site, and direction of these forces determine the magnitude of injmy. JO The brain injuries resulting from mechanical forces have long been described as primary injuries of either focal or diffuse lesion etiology. 12 The classification system devised by Gennarelli et al ir, provides insight into the pathophysiologic dynamics occurring in brain injmy and provides mutually exclusive lesion definitions for brain injuries. Focal lesions are those brain injuries that can be identified on CT scan as spaceoccupying lesions. They cause mass effect and are thought to be the cause of coma. ·Focal lesions arc defined as extraclural (epidural) hematomas and acute subdural hematomas requiring surgical intervention or other focal which may or may not have required surgery but included some component of space-occupying pathoiogy. Another type of diffuse brain lesion, is classified strictly by coma duration. Subgroups of coma duration are determined by length of coma, that coma less than 24 hours or greater than 24 hours. Those in coma from greater than 24 hours were further identified as having either
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a decerebrate or nondecerebrate component. The classification system devised by Gennarelli et al1 6 remains relevant today and provides the foundation of understanding for the primary injury caused by mechanical forces. The complexity of brain injury, however, continues to unfold as more is learned of the delayed or nonmechanical injuries. Delayed or secondary brain damage, although initiated at the time of mechanical force, is not present clinically for hours to days after injury. Secondary injuries include brain swelling (edema), alterations in the brain's endogenous neurochemical mechanisms, and ischemia. Best known to clinicians are the cerebral dynamic effects of brain injury. These include the changes in volume and pressure associated with swelling, the development of increased intracranial pressure, the shifting of cerebral spinal fluid into the intrathecal spaces, and the dependence of the brain on systemic blood pressure to maintain cerebral perfusion pressure when autoregulation is lost. Adverse changes are immediately apparent by intracranial pressure and jugular venous monitoring, calculation of cerebral perfusion pressure, and mass shifts on CT scans. Less well known or understood are the endogenous neurochemical processes that are initiated as a result of the mechanical distortion. Following injury, a cascade of events occurs that requires hours to days to complete.15 Four mechanisms have been described in the pathobiology of injury, which result in cell dysfunction and delayed cell death: receptor dysfunction, free-radical effects, inflammatory events, and calciummediated damage. 15 Two distinct physiologic injuries, those that directly damage the axon of the neuron (deafferentation) and those that cause widespread neuroexcitation, result from these injury mechanisms. For each of these injury types, specific pathophysiologic characteristics have been described and physiologic dysfunctions have been identified. Axonal injury or deafferentation injury occurs as a result of neurofilament disassembly, which leads to cytoskeletal change, impaired axonal transport, axonal swelling, and disconnection. 36· ·~ 7 Deafferentation occurs as a result of axonal disconnection (axons physically disconnect from one another) and interrupts established neuronal pathways. Neuronal dis-
connection can be diffuse, that is, scattered throughout injured tissue, or concentrated in a focused area of tissue.37 Deafferentation occurs throughout cortex and brain stem and the diffuse or focused pattern of disconnection influences rate and extent of recovery. Neuroexcitation (diffuse) injury, the second type of injury identified in TBI, has been hypothesized by Hayes et al1 7 to be a result of aberrant neuronal information flow and has been described more fully as a neuroexcitatory cascade. Activated by TBI, a neurotransmitter surge occurs as a result of depolarization and nonspecific release of neurotransmitters. In addition, there is an influx into the brain of blood-borne neurotransmitters through the damaged blood-brain barrier. When depolarization occurs, massive amounts of excitatory neurotransmitters, such as glutamate, aspartate, and acetylcholine, are released. 13· 17• 25 - 27 Depolarization is thought to occur as a result of increases in extracellular potassium brought about by mechanical deformation of potassium channels and breakdown of plasma membranes shifting potassium out of the cell. 17 In addition, calciummediated events occur, driving large amounts of calcium into the cell and causing breakdown of cell membranes and the development of free fatty acids. 15 Interestingly, this physiologic cascade of events can be initiated by injury or ischemia. Characterized as a secondary injury, the destructive power of ischemia is widespread and well documented. 5 Although often associated with raised intracranial pressure, episodes of hypoxia, and hypotension, ischemia can also occur alone. Considerable investigation has occurred over the years to determine how the ischemic process evolves. One hypothesis postulates that there is a reduction in regional cerebral blood flow during the first 6 hours after injury even in patients without surgical mass lesions. Persisting for the first 24 hours after injury, this low flow state has been associated with low Glasgow Coma Scores (GCS) and is thought to have detrimental effects on brain cell viability and neurologic recovery. A second hypothesis counters the first, suggesting ischemia is caused not by some single inherent hypoperfusion mechanism but that it occurs as the injury sequelae evolve. Brain shifts that occur with tissue swelling and increased ICP distort and stretch cerebral ves-
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sels and a hypoperfusion state. Changes in the cerebral microvasculature, vasospasm, and hypotension related to other injuries also contribute to development of ischemia. 10 Although ischemia following TEI occurs throughout the brain, the hippocampus located in the medial temporal lobe is most vulnerable to even small changes in perfusion.
Cognitive Dysfuncticn and Brain Injury Cognitive impairments following severe brain injmy are pervasive and span a range of severity from coma to forgetfulness. Cognitive dysfunction following brain injury is not similar in all patients owing to the vast numbers of possible patterns of focal and diffuse prima1y injuries and secondary injuries. Brain damage to specific areas results in an inability to interpret the signal, whereas destruction of the network results in an inability of intact brain structures to receive and interpret signals. Despite the heterogeneity of brain injmy, there are salient features of cognitive dysfunction that may occur in many patients. These features include antegrade amnesia, impaired explicit memory, attention deficit, and alterations in executive function. 24 The complex relationship between cognitive dysfunction and brain injmy is slowly emerging through multiple avenues, including psychologic and neuropsychologic testing, CT scanning, MR imaging, functional MR imaging, PET scanning, and autopsy results. Thus, it is possible to match the pathophysiologic data with the type of cognitive impairment that has been identified. Brain structures and neuronal networks associated with cognitive function seem especially vulnerable to both primary and secondary injury. An understanding of the etiology of the symptoms allows for the development of strategies that may contribute to preventing further injury or to enhancing cognitive recove1y or both. As a result of prima1y injuries, there is direct damage to brain structures. Contusions of the brain are common and are found ve1y frequently in the cortex, especially in the frontal cortex and poles of the temporal cortex. A large percentage of diffuse axonal injuries also occur in the frontal and temporal areas. In fact, the early work of Ommaya and Gen-
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narelli 35 identified the hippocampal mesocortex and temporal neocortex as being substantially injured following trauma to the head. Brain stem injmy, which is associated with rotational forces, and diffuse axonal injury are common and result in damage to the reticularactivating system. The secondary injuries that occur from swelling compromise blood supply to all cortical structures. The temporal lobe and hippocampal system structures are especially vulnerable to swelling because they are often compressed against the tentorium even if uncal herniation does not occur. Additional insult occurs to the hippocampus if hypotension, hypoxia, or hypoxemic episodes take place. These events, even if mild, easily damage the hippocampus, which is the brain structure most vulnerable to ischemia. The brain structures identified as most frequently injured are those responsible in some way for many of the cognitive functions necessary for participating in routine daily activities. One of the most striking and incapacitating cognitive impairments is the loss of recent memory. Known as antegrade amnesia, this enduring loss of declarative or explicit memory is characterized by an inability to remember recent events. Highly associated with injmy to the hippocampal system, patients with these injuries have lost the ability to encode or store information. Ability to make spatial representation and the ability to learn are also impaired. Attentional deficits have also been identified and are most likely the result of direct brain stem injury or injury to networks linking the brain stem with the prefrontal area. One impairment of attention has been described as an inability to adequately focus (selective or "phasic" attention) and another is an inability to sustain attention or concentrate. As a result of attentional deficits, TEI patients have difficulty reading, following conversations, watching a television program, or even maintaining a train of thought. 1 Severe damage to the brain stem and its connecting networks results in prolonged coma. Loss of executive functioning is quite devastating following brain injury. Without executive function, planning and organization are impaired, decision making is difficult, and judgment is compromised. Because of the complexity of this cognitive system, the prefrontal cortex or any number of its connecting
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structures or networks could be damaged and result in executive dysfunction. Although these cognitive impairments are described separately, the reality for a patient with TBI is that multiple problems need to be addressed to regain a meaningful lifestyle.
Research-Based Interventions for Cognitive Impairments Survival for patients with cognitive impairments can be attributed to the early and focused management of primary and secondary injuries. Management plans for persons with TBI must account for the ongoing process of brain damage caused by the delayed effects of injury. By allowing the focal point of therapy to target ongoing change, sequential therapies based on the evolution of the injury can be mounted. 28 • 46 An interesting duality occurs following brain injury, that is, injury mechanisms and recovery mechanisms are activated simultaneously. Unfortunately, there are no interventions to enhance cognitive function directly. Two mechanisms, however, have been identified, neuroprotection and neuroplasticity, that once activated have the potential to reduce neuronal damage or enhance neuronal growth, thereby indirectly improving cognitive function.
Neuroprotectkm Strategies The aim of neuroprotective strategies is to shield the injured brain from the delayed or secondary damage following the brain insult. Interventions that may be effective in protecting neurons from secondary injury target include (1) management of ICP and cerebral perfusion pressure (CPP) through traditional venues including medical management and positioning and (2) disruption of the neurochemical mechanisms activated by the injury cascade. The importance of delayed or secondary injury is being increasingly recognized. Recently published guidelines for the management of severe TBI, which are based on extensive reviews of the research literature, target ff·•w''"~·" cerebral blood flow to prevent ischemia. Hyperventilation (Paco 2 :::::35 mm Hg) in the acute management of brain injury is no longer advocated during the first 24
hours after injury because it causes cerebral vasoconstriction. Hyperventilation is recommended as an option of care only if neurologic deterioration occurs or if ICP is refractory to traditional treatments such as sedation, paralysis, drainage of cerebrospinal fluid (CSP), and osmotic diuresis. 7 CPP has also been targeted by the Brain Trauma Foundation. 6 The critical threshold for CPP has been set between 70 and 80 mm Hg. Although there is not sufficient empirical support for a standard of care related to maintaining CPP above 70 mm Hg, the morbidity and mortality data associate better outcomes with higher CPP. Along with these new recommendations, there is continued support for more traditional approaches to TBI management, including optimizing systemic blood pressure with vasoactive agents, maintaining euvolemia, utilizing sedation and paralyzing agents to manage metabolic demand (e.g., agitation, restlessness), and aggressive treatment of ICP elevations. 8 Another powerful intervention that can be used effectively to prevent secondary injury is patient positioning. Since the classic study by Mitchell and Mauss, 32 nurse researchers and others have investigated the effect of positioning on ICP and CPP. Reporting results of an integrated review on positioning research indicate routine standards of care are not recommended for positioning of patients with TBI. 20 Rather, the literature supports patient positioning, especially head-of-bed elevation and turning, that optimizes CPP and minimizes ICP. 20 Reduction in core body temperature has also been examined as a neuroprotective method. A preliminary trial using moderate hypothermia (i.e., temperatures of 33°C) has demonstrated a reduction in mortality and improved short-term psychologic function after brain trauma. The use of hypothermia as a neuroprotective strategy is based on the theory that the secondary injury cascade can be attenuated by lowering metabolism, which in turn reduces the posttraumatic neurochemical response. 29 It is important to note that core temperature reduction using moderate hypothermia requires a strict protocol for implementation and should not be confused with routi:r:e use of for 1f-'rnnP"'" reduction. The neurochemical cascade that follows TBI is well documented, and the pharmaco-
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logic manipulation of the associated signs and symptoms is under intense investigation. Future treatment of brain injury will undoubtedly include administering combinations of neuroprotective agents, but most likely they will be given within designated windows with an emphasis on sequence and concurrent administration. The following agents have been or are currently under investigation: anticholinergics or cholinomimetics, anti-inflammatory agents, calcium channel blockers, cal pain antagonists, free-radical scavengers, and glutamate antagonists. 29 In addition, treatments to diminish the acidosis generated by anaerobic metabolism are also being examined. 34 The hypothesized mechanisms of action of these agents are complex and beyond the scope of this article, and readers are encouraged to read the cited references. The pathobiology of TBI is complex, and the role of neuroprotective intervention spans a wide continuum. Developing successful neuroprotective strategies will occur only with continued focus on the acute and chronic sequence of events, windows of opportunity, delivery strategies, and the potential use of combinations of therapies. In the future, more innovative clinical trials will be conducted using neuroprotective agents. 29
Neuroplasticity Although slow and incomplete, cognitive and motor recovery following diffuse and axonal injury is possible. Recovery of function is thought to occur as a result of resolution of local factors such as edema but more importantly through plasticity. Plasticity has also been described as a consequence of deafferentation injury where remaining axons sprout and grow new connections. 32 Several mechanisms are thought to enhance plasticity, including the release of neurotrophic factors and environmental enrichment. Following injury, the peptide neurotrophic or growth factors are expressed. These factors induce sprouting of neurites (neuronal plasticity) and facilitate guidance of neurons to their proper targets. Nerve growth factor, basic fibroblast growth factor, brain-derived nerve growth factor, and neurotrophin-3 are just a few of the many factors identified. There is evidence that neurotrophic factors are altered following brain injury, perhaps in an
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effort to facilitate repair and reestablish functional connections. 29· 47 More recent evidence expands the role of neurotrophic factors to include damage prevention and promotion of regenerative processes after brain injury. Consequently, the integrity of neurons as well as the structure and function of neurons is preserved and long-term damage is attenuated. 28 Much of the pioneering work related to the effect of neurotrophic factors has been gleaned from animal studies. Prevention of cell death in neurons projecting to hippocampus18· 49 following ischemic and neuroexcitatory lesions 14• 40 and decreases in cognitive dysfunction associated with septal lesions 41 • 42 have been reported following administration of nerve growth factor. McDermott et al28 reported improvement in cognitive function in rats that received continuous basic fibroblast growth factor (bFGF) for 7 days following brain injury. From the research comes the notion that neurotrophic factors may have a delayed or prolonged therapeutic window, enabling administration of these types of agents beyond the critical phase of injury. Clinical use for the administration of neurotrophic factors remains under investigation. Because it seems that expression of neurotrophic factors is an advantage to recovery, treatments that may minimize or diminish their effectiveness should be scrutinized. Prophylactic use of anticonvulsants has become commonplace in the treatment of brain injury because of the untoward effects of seizures, namely, increased metabolic demand and release of excitatory neurotransmitters; however, the indiscriminate use of anticonvulsants is not without risk Schierhout and Roberts 39 systematically reviewed randomized controlled trials to examine the effectiveness and safety of antiepileptic agents in the treatment of acute TBI. Results of their review suggest that antiepileptic agents may actually delay neurologic recovery and contribute to impaired cognition and motor function. Moreover, there was no evidence that prophylactic use of antiepileptics used at any time after head injury reduced death and disability. As a result of their review, antiepileptics were recommended only in high-risk patients and during the first week after injury. Environmental manipulation has been shown to influence cognitive function and to produce long-lasting changes in neuronal
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structure. 3 Through experience-dependent mechanisms, new synapses are generated in response to experiences, and opportunities for learning can occur. Consequently, sensory stimulation paradigms using novel and meaningful stimuli have been used in an attempt to increase arousal in patients who are comatose.9· 22 • 31 Although there have been positive responses by patients to sensory stimulation programs, it is difficult to determine if positive recovery trajectories are the effect of normal brain healing or increased plasticity. Unfortunately, this question is not resolved easily in clinical studies. Useful clinical information coming from sensory stimulation research suggests it is a safe intervention even early after injury. 9 The efficacy of sensory stimulation programs for persons in coma following TBI has yet to be determined, but there is still the need to create environments that promote plasticity. It is the rich experiences of everyday life that have demonstrated positive effects on cognition after brain injury. 23 •46 Efforts should be made to use meaningful conversa-
tion, orientation techniques, arousal methods such as bells and blocks, familiar voices, and music in an attempt to promote novel environments for the healing brain. 10• 19 As patients are able to actively participate in the rehabilitation process and participate in neuropsychologic testing, the complex overlap of cognitive impairments may be better understood. The rehabilitation approach is often difficult given the multitude of impairments; however, some strategies have been useful. For memory impairments, supporting techniques and aids such as notebooks and computers are more beneficial than repetitive memory exercises. Unfortunately, researchbased strategies for managing impairments in executive dysfunction are minimal. Access to care, system services, and financial resources become priorities when planning discharge from an acute care setting. Such services should emphasize the important interaction between individuals and their environments, as this is necessary in determining real-world successes and failures. 48
SUMM.AR'ti' Brain injury is a dynamic process that continues for weeks. Recovery is also a lengthy process, proceeding in overlapping stages along with injury. The outcome for many patients with TBI is an inability to fully participate in life events because of.cognitive impairments. Physiologic responses throughout the injury an,d recovery are punctuated by neuroprotective and neuroplastic events. The time course of these injury and recovery activities requires that medical and nursing therapies. are targeted across the trajectory of injury as damage and recovery processes are occurring. Prevention of secondary injury using medical and nursing strategies should be of paramount importance. Altering the environment by .providing meaningful yet novel sensory stimulation may enhance plasticity .and lead. to reorganization of structures that support cognitive processes. Administration of neuroprotective agents in an effort to control damage from neurochemieal processes should proceed as these agents become approved fordinical use, Active participation in rehabilitation programs and rteu...... ropsychologic.testingprovide.additionala.ve:nuesfor.identifying.andaddressing. cognitive impairments. the complex relationship between injury and cognitive impairment is slowly being unraveled. Through an understanding of the brain structures and networks associated with information processing as well as the pathophysiologic consequences of brain injury, critical care nurses can design evidence-based regimens of care that preserve cognitive function and result in improvement of long-term cognitive outcomes and fuller participation in everyday life activities.
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REFEREf\JCES 1. Arcinieg,1s D, Adler L. TopkoffJ, et al: Attention and memory dysfunction after traumatic brain injury: Cholinergic n1echanisn1s, sensory gating, and a hypothesis for further investigation. Brain Injury 13:113, 1999 2. Bach-y-Rita P: Brain plasticity as a basis for recovery of function in humans. Neuropsychulogia 28:547554, 1990 3. BlackJ, Greenough W: Induction of pattern in neural structure by experience: Implications for cognitive development. Jn Lamb M, Brown A, Rogoff U (eds): Advances in Developmental Psychology, vol 4. Hillsdale, NJ, Lawrence Earlbaum AssocL1tes, pp 1-50 4. Boller F, Traykov L, Dao-Castellana M, et al: Cognitive functioning in "diffuse pathology": Role of prefrontal and limbic structures. Ann N Y Acad Sci 769:2339, 1995 S. Bouma G, MuizelaarJ, Chui S, et al: Cerebral circulation and metabolism aftccr severe traumatic brain injury: The elusive role of ischemia. J Neurosurg 75:685-693, 1991 6. Brain Trauma Foundation: Guidelines for cerebral perfusion pressure. J >Jeurotrauma 13:693-703, 1996 7. Brain Trauma Foundation: Use of hyperventilation in the acute management of sevc:re traumatic brain injury. J Neurotrauma 13:699-703, 1996 8. Davis A, Briones T: Intracranial disorders. In Kinney M, Dunbar S, Vitello J, et al (eels): AACN Clinical Reference for Critical Care: Nurses, eel 4. St Louis, Mosby, 1998 9. Davis A, Gimenez A: Auditory sensory stimulation in comatose brain injured patients (manuscript in preparation) 10. Davis A, White ]: Innovative sens01y input for the comatose brain injured patient. Crit Care Clin North Am 7:351-361, 1995 11. Eichenbaum H, Cohen N, \'Vibble C: Memory and learning: A snapshot without an album. Brain Res Rev 16:193-220, 1991 12. Emilien G, Waltregny A: Traumatic brain injury, cognitive and emotional dysfunction: Impact of clinical neuropsychology research. Acta Neurologica Belg 96:89-101, 1996 13. Faden A, Demediuk P, Panter S, et al: The role of excitalo1y amino acids and NMDA receptors in traumatic brain injury. Science 244:798-800, 1989 14. Frim D, Short M. Rosenberg \YI, et al: Local protective effects of nerve growth factor-secreting fibroblasts against excitotoxic lesions in the rat striatum. Neurosurge1y 78:267-273, 1993 15. Gennarelli T: The pathobiology of traumatic brain injury. The Neuroscientist 3:73-80, 1997 16. Gennarelli T, Langfitt T, Harrington T, et al: Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg 56:26-32, 1982 17. Hayes R, Jenkins L, Lyeth B: Neurotransmitter-medi:ited mechanisms of traumatic brain inju1y: Acetylcholine and excitatory amino acids. ] Neurotrauma (suppl) 9:173-187, 1992 18. Hefti F: Nerve growth factor promotes survival of septa! cholinergic neurons after fimbrial transections. J Neuroscience 6:2155-2162, 1986
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