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This chapter includes an accompanying lecture presentation that has been prepared by the author: .
This chapter includes an accompanying lecture presentation that has been prepared by the author: .
Differences in the probabilities and time frames of recovery from coma, vegetative state (VS), or minimally conscious state (MCS) reflect specific cellular and circuit-level mechanisms underlying the pathophysiology of each state and the general mechanism of recovery of forebrain arousal.
Recent practice guideline recognize that outcomes of better than severe disability differ for MCS and VS patients, with many MCS patients demonstrating a wide range of later recovery.
Functional magnetic resonance imaging (fMRI) or functional electroencephalography (fEEG) techniques can be used to identify conscious command following in behaviorally unresponsive patients.
Cognitive motor dissociation (CMD) denotes such patients with only fMRI or fEEG evidence for command following or higher integrative functions demonstrated using these tools.
Altered consciousness after brain injury is associated with several clinical syndromes, including coma, vegetative state (VS), minimally conscious state (MCS), akinetic mutism, and other related conditions. In this chapter a clinically oriented review is presented with emphasis on mechanisms that underlie altered consciousness at the neuronal “circuit” level. A brief taxonomy of altered states of consciousness is presented, followed by a discussion of general strategies to assess patients and formulate a diagnosis and prognosis. The considerable differences in probabilities and time frames of recovery from disorders of consciousness can best be understood in the context of the specific cellular and circuit-level factors that underlie the pathophysiology of individual brain injuries and the general mechanisms of forebrain arousal. The potential contribution of new neuroimaging modalities and theoretical models to the diagnostic assessment of patients with disorders of consciousness is briefly reviewed. An emerging understanding of mechanisms underlying recovery of consciousness (ROC) is improving the discrimination of these conditions and is expected to advance clinical practice. Finally, a newly emerging understanding of the presence of preserved high-level integrative brain activity in patients appearing to remain in a disorder of consciousness in acute intensive care unit, subacute care, and chronic care settings is reviewed. The term cognitive motor dissociation (CMD) is defined and the emerging implications for both treatment and prognosis in this subgroup of patients are considered.
Altered consciousness is among the most common finding in patients evaluated by a consulting neurosurgeon or neurologist. The development of a comprehensive differential diagnosis, treatment plan, and prognosis for altered consciousness is well beyond the scope of a single book chapter (instead, see Posner and colleagues ). Here, emphasis is placed on conceptualizing neurological disorders of consciousness and formulating an organized and physiologically based approach to the general set of problems. A systematic approach to evaluate patients with altered consciousness requires a foundation of the basic principles that underlie maintenance of the normal wakeful conscious state.
Schiff and Plum proposed the following working definition for the normal wakeful conscious state in humans modeled after that of James (1894):
At its least, normal human consciousness consists of a serially time-ordered, organized, restricted and reflective awareness of self and the environment. Moreover, it is an experience of graded complexity and quantity.
Human conscious brain states are characterized by several neuropsychological components, including arousal, attention, intention, memory, awareness, and mood-emotion. A clinically oriented view of global disorders of consciousness suggests a roughly hierarchical organization of these components. The baseline arousal level appears to influence all neuropsychological functions in humans and animals, and absence of an alert, awake state precludes behavior. Complete loss of patterned arousal is seen only in coma and in brain death. In VS, limited recovery of arousal patterning occurs without evidence of the other neuropsychologic components of human consciousness. Fragmentary elements of specific neuropsychologic components are evident in the syndromes of VS and MCS. For example, fragments of attentional function are evidently preserved in all forms of akinetic mutism, with varying levels of impairment in other components. Similarly, purposeless intentional movements can occur in patients with hyperkinetic mutism or as partially integrated and organized goal-directed sensorimotor activity in those with complex partial seizures or delirium. Complex brain injuries typically produce a mix of the clinical features observed in these classical syndromes. Here we focus on the classification of global disorders of consciousness most frequently encountered and related to one another as recovery evolves after severe brain injury.
Coma is an unconscious brain state characterized by the total absence of patterned behavioral arousal or electroencephalographic features of the sleep-wake architecture. Comatose patients remain motionless in an eyes-closed state without spontaneous periods of eye opening or change of state with vigorous stimulation. Although effortful stimulation of a comatose patient may produce a grimace in response to painful stimuli or stereotyped withdrawal movements of the limbs generated by spinal reflexes, these movements lack localization of the source of external stimulation and the organized sequence of movements associated with purposeful avoidance. Patients in deep levels of coma typically do not exhibit primitive reflex responses.
By definition, the term coma implies that the state has endured for at least 1 hour, and in some clinical operational definitions for at least 6 hours. Nonetheless, coma is invariably a transient condition that if uncomplicated by concurrent systemic illness, sedation, or other similar factors typically does not persist beyond 10 to 14 days in those patients who survive. Although some patients quickly pass through coma, many others transition through functional stages of VS and MCS (defined later).
The concept of VS was first introduced in 1972 by Jennett and Plum, who defined the clinical syndrome of the “persistent vegetative state” as being identified by dissociation of an apparent recovery of behavioral wakeful arousal associated with periods of eye opening that alternate with periods of eye closure in patients who show no evidence of awareness of self or their environment. Early use of the term arbitrarily identified VS lasting longer than 30 days as a “persistent vegetative state.” However, many organizations and countries have now advocated that the modifier “persistent” not be used because it is often misinterpreted to indicate probable permanence of the VS. The expectation for permanence of the VS can be assessed accurately only by considering the mechanism and elapsed time from the injury. In addition, the term “unresponsive wakefulness syndrome” (UWS), borrowing from Jennett and Plum’s original definition of VS, has been used as a substitute designation.
The VS typically follows an initial coma produced by an acute brain insult and most often is associated with patterns of injury that overlap those that produce coma. The two most common causes of VS are severe traumatic brain injury and ischemic injury from cardiac arrest. Autopsy studies of patients who remain in VS after both conditions demonstrate a common pattern of extensive loss of thalamic neurons, particularly within the central thalamic intralaminar nuclei and closely adjacent components of thalamic association nuclei. Bilateral injuries restricted to these regions alone can produce coma. , The severe loss of thalamic neurons reflects widespread disconnection of the corticothalamic system and neuronal death across the cerebrum. Although this finding of extensive thalamic neuronal loss can be seen after both diffuse axonal injury from brain trauma and oxygen deprivation associated with cardiac arrest, widespread neocortical neuronal death is common only with cardiac arrest (64% versus 11% ). Significant brainstem damage is not commonly found at autopsy of VS arising from either etiology, an observation that emphasizes that VS is primarily a disorder of corticothalamic system integration.
Since the original definition of VS, research efforts have typically focused on clinical indicators of permanence and underlying neuropathology as reviewed by Jennett. A small number of early neuroimaging studies of VS patients measured cerebral metabolism with fluorodeoxyglucose–positron emission tomography (FDG-PET) scans. In these studies, VS patients showed a reproducible reduction in resting metabolism to typically 30% to 50% of normal metabolic rates across cerebral structures. , Comparable reductions in cerebral metabolic rates are found in normal subjects in the pharmacologic coma produced by surgical anesthesia. Investigations by several groups have identified functional activation of cerebral networks in response to sensory stimuli in VS patients by using functional neuroimaging methods (oxygen 15 [ 15 O]-PET and functional magnetic resonance imaging [fMRI]). These studies have demonstrated widespread failure of functional responses to elementary sensory stimuli in cortical regions remote from the primary sensory cortices in VS patients. , In some VS patients, unusual behavioral and physiologic variations are correlated with evidence of isolated islands of metabolic activity. In one such VS patient, rare single understandable words were emitted for 20 years without linkage to environmental stimulation. In this patient the left cerebral structures (including the Wernicke area in the temporal association cortex and the Broca area in the frontal opercular region) demonstrated relatively increased metabolic rates (nearly twice the rates in surrounding brain tissue) and physiologic connections consistent with partial and isolated preservation of brain structures of the human language system. The behavioral fragments more typically identified in chronic VS patients are stereotyped emotional-limbic responses such as grimaces. These emotional displays most probably reflect isolated limbic networks tightly linked to brainstem and basal forebrain structures that operate without functional connection to the thalamocortical systems that are typically severely damaged in VS patients.
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