Neurorehabilitation in Disorders of Consciousness
Estimates of misdiagnosis among patients with disorders of consciousness have been very high, ranging from 37 to 43% in some studies. It was thought that accuracy should be higher, after diagnostic criteria for a minimally conscious state were established in 2002; however, a more recent study on diagnostic accuracy showed otherwise. Using a standardized assessment instrument the CRS-R as the gold standard, the authors found that 41% of the diagnoses established by expert team consensus were incorrect, 89% of which were in the false-negative direction (i.e., conscious, but believed to be unconscious). This rate is equivalent to the rates reported before the criteria for a minimally conscious state were published.
Many factors have been implicated as causes of diagnostic error in disorders of consciousness, including patient, examiner, and environmental influences. There are several common problems that can lead to inaccurate diagnosis in patients with impaired consciousness. These include attributing purposeful intent to behaviors that are nonpurposeful, reflexive, or generalized responses; inadequate evaluation to detect conscious behavior, such as insufficient sampling time, inadequate arousal, inappropriate choice of stimuli; failure to account for sensory, motor, or cognitive impairments that confound assessment results; over- or underconsideration of family or other's observations of purposeful behavior (i.e., failure to recognize that family may be first to observe signs of consciousness or to overattribute purposeful intent); and overattributing intent to simple, cortically mediated behaviors of uncertain cognitive significance, such as simple isolated limb movements.
To improve diagnostic accuracy and provide another means to assess cognitive awareness and intent, investigational procedures have been developed using functional magnetic resonance imaging and recently electrophysiologic techniques (i.e., evoked response potentials, quantitative electroencephalogram [EEG]) to assess brain activity during different activation protocols. The protocols involve passive paradigms, such as presentation of speech or complex visual stimuli, or active paradigms, such as imagining a sporting activity or navigating through a familiar environment. Consciousness is inferred when the pattern of brain activity is analogous to controls. Although there is correspondence with behavioral evaluations much of the time, there is sometimes incongruity between findings on behavioral examinations and functional imaging. Large studies assessing the sensitivity and specificity of these assessment techniques, in comparison to behavioral evaluation, have not been published.
Interpretation of reports of the range of medical problems seen after brain injury is complicated by the differences in the populations being described and the criteria for diagnosis and resolution, with no standardized population-based surveys available. The medical comorbidities accompanying severe brain injury depend on the etiology of the brain injury and age of the sample (i.e., those who have suffered anoxic injuries are likely to have more age-related and cardiovascular comorbidities than those with traumatic injuries), on the site of care and time postinjury (i.e., patients receiving early acute care typically have more comorbidities than those in later subacute care). Evidence from a recent study of patients with TBI cared for in acute rehabilitation hospitals found that the rate of new medical problems declined in relation to time in rehabilitation, rather than time postinjury, suggesting that active management rather than the mere passage of time accounts for this reduction.
Most patients admitted to rehabilitation following a severe brain injury come with a long problem list developed in the acute care facility and linked with a set of ongoing treatments. Thus, the initial task of the rehabilitation specialist is to assess the status of those problems and to determine whether the current treatment regimen should be continued, terminated, or modified. In many instances, a treatment begun acutely may no longer be needed as recovery proceeds. For example, a patient may have been started on metoclopramide for gastroparesis, but as time passes, gastric motility may improve. Thus, the physician should review the problem list for issues that may be resolving and attempt treatment withdrawal where indicated, while carefully monitoring relevant signs or symptoms.
In other instances, it may be clear that the problem continues, but that the management could be optimized from a rehabilitation perspective. For example, a patient with severe hypertonia may be treated with large doses of an oral antispasticity medication with only moderate benefit and considerable sedation. The rehabilitation team may entertain the possibility of selective local injections of botulinum toxin for the most severe areas of hypertonia, or in cases where extreme hypertonia is widespread, may proceed to an early evaluation of intrathecal baclofen, thus allowing reduction or elimination of the oral antispasticity agent.
Relatively few drugs have been rigorously tested for their effects on cognition and still less is known about their effects on minimally conscious patients. Thus, the clinician must weigh the possibility that a level of sedation that would have trivial effects on a fully conscious patient might substantially impair an individual with inconsistent alertness.
Identification of Occult Problems. Patients with posttraumatic disorders of consciousness may suffer from occult problems that have not yet been diagnosed because of attention to more pressing diagnoses or because the patient's level of consciousness or movement did not allow symptoms to be manifested. Pain (or nociceptive responses in the unconscious patient) is an important source of diagnostic information for many medical problems, but systematic assessment of pain in patients with disorders of consciousness is challenging, and no fully validated observational pain measure exists. Moreover, behaviors such as facial grimacing that are typically associated with pain may occur for other reasons in the context of significant brain damage. Thus, nondisplaced fractures can be missed until that patient's level of consciousness allows greater communication about sources of pain. Peripheral nerve lesions or "critical illness polyneuropathy" can be overlooked when masked by central paralysis, but as tone or volitional movement emerge, focal weakness may become apparent. Similarly, specific cognitive deficits may become apparent as consciousness improves, as when aphasia is identified as a patient begins attempted communication.
Several medical problems that are relatively common after severe brain injury require screening for early identification. For example, reduction of thyroid, growth, or sex hormones may occur without obvious symptoms, and nonconvulsive status epilepticus, hydrocephalus, or sleep apnea may suppress consciousness without obvious clinical manifestations. Unfortunately, rigorous studies to guide the timing and appropriateness of screening for such problems are not available. Moreover, outcomes of clinical treatment of these problems does not provide clear evidence of the value of screening because patients may show clinical improvements without resolution of certain medical problems and others may fail to improve because of the inherent severity of their brain damage despite effective treatment of an important medical comorbidity.
Presentation of New Problems. Patients with severe brain damage present with a range of new problems over time. In a recent clinical trial conducted within a few months of injury, TBI patients presented with a new or worsening problem approximately every 2 weeks. Some were related to the ongoing risks of immobility and artificial respiration and feeding, including pneumonia, urinary tract infection, and pressure ulcers. Others were related to ongoing evolution of the neurologic injury, including development or worsening of hypertonia and contractures, and emergence of posttraumatic agitation. The remainder was problems related to the brain injury, but that could not be manifested until a certain amount of recovery had occurred, such as the onset of depression or identification of a significant balance problem. Thus, particularly in the first weeks and months after injury, close medical monitoring to identify and manage newly emerging problems is necessary.
Preparing for Future Management. Some patients with severe brain injury will undergo rapid functional recovery and with that recovery, their risks for several medical problems, particularly those related to immobility, tend to diminish. Research suggests, however, that even those with good motor function have an elevated risk of death from cardiovascular causes, which might suggest that current measures of mobility independence fail to reflect more vigorous aspects of fitness and/or that some individuals with good motor function lack the initiation to engage in substantial physical activity.
Other patients, unfortunately, fail to show substantial functional gains in the early weeks and months postinjury, although, particularly in the case of traumatic injuries, such recovery may still be manifested relatively late. Regardless of the ultimate prognosis for functional recovery, in the current health care environment, such patients rarely remain in high-intensity treatment settings long enough for substantial functional improvement; therefore, plans must be made for their care at home or in skilled nursing facilities. When this transition occurs, the simpler the patient's plan of care the more feasible it will be for family members or resource-constrained facilities to carry it out. Thus, as the time for discharge nears, particular attention should be given to the streamlining of care. For example, the rehabilitation facility may assess the feasibility of fewer tube feedings of larger volumes, and may attempt to decannulate the patient to reduce respiratory care needs. Assessment of the patient's skin tolerance for less-frequent nighttime turning, in combination with a special mattress, and consolidation of medication administration into fewer doses of longer-acting drugs will also reduce the care burden. Aggressive control of hypertonia and fabrication of resting splints may simplify contracture prevention and lower the risk of skin breakdown.
In the United States, the predominant model of care for individuals with severe brain injury and disorders of consciousness provides for only a brief interval of intensive specialty medical care. During the acute care stay, such patients have access to a full range of medical specialists who can see them daily or more often, typically including early rehabilitation consultation. However, those patients who remain unconscious or who are minimally conscious but with relatively slow clinical evolution, as their medical status stabilizes, are typically referred directly to nursing care facilities or sent home with family caregivers, bypassing specialty rehabilitation care and losing easy access to specialty care of all kinds. In many nursing care facilities, the patient may be seen weekly by a primary care physician, but have no organized oversight by a rehabilitation physician with expertise in brain injury. Given the frequency, severity, and brain injury-relatedness of many of the medical problems seen in such patients it is difficult to imagine that such a care system is optimal, and though systematic data are lacking, the frequency of transfer back to acute care for emerging medical complications is high. The disconnection of patients with disorders of consciousness from specialty care also has the negative effect of greatly limiting research in this population because patients dispersed among family homes and nonspecialized nursing facilities are difficult to identify and enroll in studies.
Alternatives to this model of care exist, however, both within the United States and elsewhere in the developed world. In the United States, patients in the Veterans Administration health care system typically receive a 90-day trial of rehabilitation in a high-intensity specialized setting. Many patients injured at work and covered by Workers' Compensation insurance, also are typically placed in rehabilitation settings after leaving acute care, suggesting, in their estimation at least, that high-quality early rehabilitation is ultimately cost effective to payers responsible for both custodial care and rehospitalizations. In Europe, there are models where all patients, regardless of the degree or pace of progress, are admitted for several months to specialized regional brain injury rehabilitation facilities (personal communication, A. Nordenbo) as well as models with a porous boundary between intensive care and rehabilitation, which allows rehabilitation to proceed interwoven with management of acute medical problems.
In 2006, a model of care recommended by expert consensus was published as the Mohonk Report after being presented to the United States Congress. In brief, the model involves three types of facilities, working in collaboration to optimize care. After stabilization in acute care, all patients with persistent disorders of consciousness would be referred to an inpatient rehabilitation facility with substantial specialized expertise in severe brain injury. These facilities would carefully assess cognitive and functional status and measure its evolution over time, while conducting the kinds of screening and medical management described above that serve to identify and manage additional medical risks and put in place optimal care plans. Patients who fail to make substantial functional gains by the time these medical goals have been accomplished, would be transitioned to skilled nursing facilities that maintain some degree of neurologic specialization, and that receive a modestly increased rate of reimbursement in recognition of these added services. Patients transitioned to such sites would retain a consultative link with the referring rehabilitation facility to facilitate communication about and management of changes in medical status, and to longitudinally monitor functional recovery and consider new opportunities for rehabilitation intervention when appropriate. A third tier of facilities, composed primarily of academic medical centers, would provide emerging assessments and treatments and organize prognostic and treatment research on the population in this care system.
Ideally, such a model system of care could be compared with the current predominant model with respect to both improvement in functional outcomes and costs of care. Unfortunately, at the present time, lack of clear identifiers in public administrative databases of patients with disorders of consciousness, the fact that different parts of the care system are paid for by different entities, and the presence of systematic biases in socioeconomic status, age, and other factors in those who receive more versus less-intensive rehabilitation, preclude a rigorous comparison of systems. Nevertheless, the high rate of observed functional recovery of this population when cared for in rehabilitation systems the frequency of severity of the medical problems documented and even the reported death rates, provide circumstantial evidence for the importance of combining high-quality medical management with expert rehabilitation in the early months after severe brain injury.
Differential Diagnosis and Functional Outcome
Diagnostic Error
Estimates of misdiagnosis among patients with disorders of consciousness have been very high, ranging from 37 to 43% in some studies. It was thought that accuracy should be higher, after diagnostic criteria for a minimally conscious state were established in 2002; however, a more recent study on diagnostic accuracy showed otherwise. Using a standardized assessment instrument the CRS-R as the gold standard, the authors found that 41% of the diagnoses established by expert team consensus were incorrect, 89% of which were in the false-negative direction (i.e., conscious, but believed to be unconscious). This rate is equivalent to the rates reported before the criteria for a minimally conscious state were published.
Many factors have been implicated as causes of diagnostic error in disorders of consciousness, including patient, examiner, and environmental influences. There are several common problems that can lead to inaccurate diagnosis in patients with impaired consciousness. These include attributing purposeful intent to behaviors that are nonpurposeful, reflexive, or generalized responses; inadequate evaluation to detect conscious behavior, such as insufficient sampling time, inadequate arousal, inappropriate choice of stimuli; failure to account for sensory, motor, or cognitive impairments that confound assessment results; over- or underconsideration of family or other's observations of purposeful behavior (i.e., failure to recognize that family may be first to observe signs of consciousness or to overattribute purposeful intent); and overattributing intent to simple, cortically mediated behaviors of uncertain cognitive significance, such as simple isolated limb movements.
To improve diagnostic accuracy and provide another means to assess cognitive awareness and intent, investigational procedures have been developed using functional magnetic resonance imaging and recently electrophysiologic techniques (i.e., evoked response potentials, quantitative electroencephalogram [EEG]) to assess brain activity during different activation protocols. The protocols involve passive paradigms, such as presentation of speech or complex visual stimuli, or active paradigms, such as imagining a sporting activity or navigating through a familiar environment. Consciousness is inferred when the pattern of brain activity is analogous to controls. Although there is correspondence with behavioral evaluations much of the time, there is sometimes incongruity between findings on behavioral examinations and functional imaging. Large studies assessing the sensitivity and specificity of these assessment techniques, in comparison to behavioral evaluation, have not been published.
Prevalence of Medical Problems
Interpretation of reports of the range of medical problems seen after brain injury is complicated by the differences in the populations being described and the criteria for diagnosis and resolution, with no standardized population-based surveys available. The medical comorbidities accompanying severe brain injury depend on the etiology of the brain injury and age of the sample (i.e., those who have suffered anoxic injuries are likely to have more age-related and cardiovascular comorbidities than those with traumatic injuries), on the site of care and time postinjury (i.e., patients receiving early acute care typically have more comorbidities than those in later subacute care). Evidence from a recent study of patients with TBI cared for in acute rehabilitation hospitals found that the rate of new medical problems declined in relation to time in rehabilitation, rather than time postinjury, suggesting that active management rather than the mere passage of time accounts for this reduction.
Assessment of Ongoing Management Strategies
Most patients admitted to rehabilitation following a severe brain injury come with a long problem list developed in the acute care facility and linked with a set of ongoing treatments. Thus, the initial task of the rehabilitation specialist is to assess the status of those problems and to determine whether the current treatment regimen should be continued, terminated, or modified. In many instances, a treatment begun acutely may no longer be needed as recovery proceeds. For example, a patient may have been started on metoclopramide for gastroparesis, but as time passes, gastric motility may improve. Thus, the physician should review the problem list for issues that may be resolving and attempt treatment withdrawal where indicated, while carefully monitoring relevant signs or symptoms.
In other instances, it may be clear that the problem continues, but that the management could be optimized from a rehabilitation perspective. For example, a patient with severe hypertonia may be treated with large doses of an oral antispasticity medication with only moderate benefit and considerable sedation. The rehabilitation team may entertain the possibility of selective local injections of botulinum toxin for the most severe areas of hypertonia, or in cases where extreme hypertonia is widespread, may proceed to an early evaluation of intrathecal baclofen, thus allowing reduction or elimination of the oral antispasticity agent.
Relatively few drugs have been rigorously tested for their effects on cognition and still less is known about their effects on minimally conscious patients. Thus, the clinician must weigh the possibility that a level of sedation that would have trivial effects on a fully conscious patient might substantially impair an individual with inconsistent alertness.
Identification of Occult Problems. Patients with posttraumatic disorders of consciousness may suffer from occult problems that have not yet been diagnosed because of attention to more pressing diagnoses or because the patient's level of consciousness or movement did not allow symptoms to be manifested. Pain (or nociceptive responses in the unconscious patient) is an important source of diagnostic information for many medical problems, but systematic assessment of pain in patients with disorders of consciousness is challenging, and no fully validated observational pain measure exists. Moreover, behaviors such as facial grimacing that are typically associated with pain may occur for other reasons in the context of significant brain damage. Thus, nondisplaced fractures can be missed until that patient's level of consciousness allows greater communication about sources of pain. Peripheral nerve lesions or "critical illness polyneuropathy" can be overlooked when masked by central paralysis, but as tone or volitional movement emerge, focal weakness may become apparent. Similarly, specific cognitive deficits may become apparent as consciousness improves, as when aphasia is identified as a patient begins attempted communication.
Several medical problems that are relatively common after severe brain injury require screening for early identification. For example, reduction of thyroid, growth, or sex hormones may occur without obvious symptoms, and nonconvulsive status epilepticus, hydrocephalus, or sleep apnea may suppress consciousness without obvious clinical manifestations. Unfortunately, rigorous studies to guide the timing and appropriateness of screening for such problems are not available. Moreover, outcomes of clinical treatment of these problems does not provide clear evidence of the value of screening because patients may show clinical improvements without resolution of certain medical problems and others may fail to improve because of the inherent severity of their brain damage despite effective treatment of an important medical comorbidity.
Presentation of New Problems. Patients with severe brain damage present with a range of new problems over time. In a recent clinical trial conducted within a few months of injury, TBI patients presented with a new or worsening problem approximately every 2 weeks. Some were related to the ongoing risks of immobility and artificial respiration and feeding, including pneumonia, urinary tract infection, and pressure ulcers. Others were related to ongoing evolution of the neurologic injury, including development or worsening of hypertonia and contractures, and emergence of posttraumatic agitation. The remainder was problems related to the brain injury, but that could not be manifested until a certain amount of recovery had occurred, such as the onset of depression or identification of a significant balance problem. Thus, particularly in the first weeks and months after injury, close medical monitoring to identify and manage newly emerging problems is necessary.
Preparing for Future Management. Some patients with severe brain injury will undergo rapid functional recovery and with that recovery, their risks for several medical problems, particularly those related to immobility, tend to diminish. Research suggests, however, that even those with good motor function have an elevated risk of death from cardiovascular causes, which might suggest that current measures of mobility independence fail to reflect more vigorous aspects of fitness and/or that some individuals with good motor function lack the initiation to engage in substantial physical activity.
Other patients, unfortunately, fail to show substantial functional gains in the early weeks and months postinjury, although, particularly in the case of traumatic injuries, such recovery may still be manifested relatively late. Regardless of the ultimate prognosis for functional recovery, in the current health care environment, such patients rarely remain in high-intensity treatment settings long enough for substantial functional improvement; therefore, plans must be made for their care at home or in skilled nursing facilities. When this transition occurs, the simpler the patient's plan of care the more feasible it will be for family members or resource-constrained facilities to carry it out. Thus, as the time for discharge nears, particular attention should be given to the streamlining of care. For example, the rehabilitation facility may assess the feasibility of fewer tube feedings of larger volumes, and may attempt to decannulate the patient to reduce respiratory care needs. Assessment of the patient's skin tolerance for less-frequent nighttime turning, in combination with a special mattress, and consolidation of medication administration into fewer doses of longer-acting drugs will also reduce the care burden. Aggressive control of hypertonia and fabrication of resting splints may simplify contracture prevention and lower the risk of skin breakdown.
Implications for a System of Care
In the United States, the predominant model of care for individuals with severe brain injury and disorders of consciousness provides for only a brief interval of intensive specialty medical care. During the acute care stay, such patients have access to a full range of medical specialists who can see them daily or more often, typically including early rehabilitation consultation. However, those patients who remain unconscious or who are minimally conscious but with relatively slow clinical evolution, as their medical status stabilizes, are typically referred directly to nursing care facilities or sent home with family caregivers, bypassing specialty rehabilitation care and losing easy access to specialty care of all kinds. In many nursing care facilities, the patient may be seen weekly by a primary care physician, but have no organized oversight by a rehabilitation physician with expertise in brain injury. Given the frequency, severity, and brain injury-relatedness of many of the medical problems seen in such patients it is difficult to imagine that such a care system is optimal, and though systematic data are lacking, the frequency of transfer back to acute care for emerging medical complications is high. The disconnection of patients with disorders of consciousness from specialty care also has the negative effect of greatly limiting research in this population because patients dispersed among family homes and nonspecialized nursing facilities are difficult to identify and enroll in studies.
Alternatives to this model of care exist, however, both within the United States and elsewhere in the developed world. In the United States, patients in the Veterans Administration health care system typically receive a 90-day trial of rehabilitation in a high-intensity specialized setting. Many patients injured at work and covered by Workers' Compensation insurance, also are typically placed in rehabilitation settings after leaving acute care, suggesting, in their estimation at least, that high-quality early rehabilitation is ultimately cost effective to payers responsible for both custodial care and rehospitalizations. In Europe, there are models where all patients, regardless of the degree or pace of progress, are admitted for several months to specialized regional brain injury rehabilitation facilities (personal communication, A. Nordenbo) as well as models with a porous boundary between intensive care and rehabilitation, which allows rehabilitation to proceed interwoven with management of acute medical problems.
In 2006, a model of care recommended by expert consensus was published as the Mohonk Report after being presented to the United States Congress. In brief, the model involves three types of facilities, working in collaboration to optimize care. After stabilization in acute care, all patients with persistent disorders of consciousness would be referred to an inpatient rehabilitation facility with substantial specialized expertise in severe brain injury. These facilities would carefully assess cognitive and functional status and measure its evolution over time, while conducting the kinds of screening and medical management described above that serve to identify and manage additional medical risks and put in place optimal care plans. Patients who fail to make substantial functional gains by the time these medical goals have been accomplished, would be transitioned to skilled nursing facilities that maintain some degree of neurologic specialization, and that receive a modestly increased rate of reimbursement in recognition of these added services. Patients transitioned to such sites would retain a consultative link with the referring rehabilitation facility to facilitate communication about and management of changes in medical status, and to longitudinally monitor functional recovery and consider new opportunities for rehabilitation intervention when appropriate. A third tier of facilities, composed primarily of academic medical centers, would provide emerging assessments and treatments and organize prognostic and treatment research on the population in this care system.
Ideally, such a model system of care could be compared with the current predominant model with respect to both improvement in functional outcomes and costs of care. Unfortunately, at the present time, lack of clear identifiers in public administrative databases of patients with disorders of consciousness, the fact that different parts of the care system are paid for by different entities, and the presence of systematic biases in socioeconomic status, age, and other factors in those who receive more versus less-intensive rehabilitation, preclude a rigorous comparison of systems. Nevertheless, the high rate of observed functional recovery of this population when cared for in rehabilitation systems the frequency of severity of the medical problems documented and even the reported death rates, provide circumstantial evidence for the importance of combining high-quality medical management with expert rehabilitation in the early months after severe brain injury.