Altered Consciousness

Published on 13/03/2015 by admin

Last modified 13/03/2015

Print this page

This article have been viewed 1418 times

CHAPTER 12 Altered Consciousness

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 coma, VS, or MCS can best be understood in the context of the specific factors that underlie the pathophysiology of individual brain injuries and the general mechanisms of forebrain arousal. Finally, the potential contribution of new neuroimaging modalities to the diagnostic assessment of patients with disorders of consciousness is briefly reviewed. Although many challenges currently limit the clinical application of these techniques, greater future roles may be anticipated.

Altered consciousness is a 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 ¹). 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.

A Brief Taxonomy

Schiff and Plum ² proposed the following working definition for the normal wakeful conscious state in humans modeled after that of James³ (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 arousal level appears to influence all neuropsychological functions in humans and animals, and absence of an aroused state precludes behavior.⁴ Complete loss of patterned arousal is seen only in coma (and in brain death, which is operationally defined and an unambiguous condition equivalent to death⁵). In VS, limited recovery of arousal patterning occurs without evidence of the other neuropsychological components of human consciousness (see discussion later). Fragmentary elements of specific neuropsychological components are evident in these syndromes. For example, fragments of attentional function are evidently preserved in all forms of akinetic mutism, with varying levels of impairment in other components (see later). 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 (see Schiff and Plum² for a more extended review). Complex brain injuries typically produce a mix of the clinical features observed in these classic syndromes. Here we focus on the classification of global disorders of consciousness most frequently encountered and related to each other as recovery evolves after severe brain injury.

Coma

Coma is an unconscious brain state characterized by the total absence of patterned behavioral arousal or electroencephalographic features of 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. Although some patients quickly pass through coma, many others transition through functional stages of VS and MCS (defined later).

Vegetative State

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.⁶ 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 (see “Guide to Prognosis” later).

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 cardiac arrest. Autopsy studies of patients who remain in VS after both conditions demonstrate a common pattern of extensive loss of thalamic neurons,⁷ particularly within the central thalamic intralaminar nuclei and closely adjacent components of thalamic association nuclei.⁸ Bilateral injuries restricted to these regions alone can produce coma.²^,⁹ 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%⁷). Significant brainstem damage is not commonly found at autopsy of VS patients, 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 (reviewed by Jennett ¹⁰). 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.¹¹^,¹² Comparable reductions in cerebral metabolic rates are found in normal subjects in the pharmacologic coma produced by surgical anesthesia.¹³ More recently, several groups have examined functional activation of cerebral networks in response to sensory stimuli in VS patients by using functional neuroimaging methods (¹⁵O-PET and functional magnetic resonance imaging [fMRI)]. These studies demonstrate widespread failure of functional responses to elementary sensory stimuli in cortical regions remote from the primary sensory cortices in VS patients.¹⁴^,¹⁵ In some VS patients, unusual behavioral and physiologic variations are correlated with evidence of isolated islands of metabolic activity.¹⁶ 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 Wernicke’s area in the temporal association cortex and Broca’s 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.¹⁷ 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.

Minimally Conscious State

The first level of behavioral recovery beyond VS is operationally defined as MCS. MCS patients show evidence on bedside examination of contingent responses to environmental stimuli or self-initiated behavior that provides unequivocal but inconsistent evidence of awareness of self or the environment ¹⁸ (Table 12-1). A wide range of behavioral expressions are currently consistent with the operational criteria for MCS.¹⁹ For example, consistent and sustained visual tracking or fixation may be the only behavioral evidence of responsiveness in an MCS patient. Alternatively, an MCS patient may exhibit intermittent spoken language responses or inconsistent and inaccurate communication with gestural or verbal output. Recovery of functional communication (operationally defined as the ability to consistently and accurately answer simple contextual yes or no questions) defines the upper boundary of MCS. Beyond MCS, varying levels of severe disability are not currently subcategorized.

TABLE 12-1 Aspen Working Group Criteria for Clinical Diagnosis of the Minimally Conscious State

From Giacino JT, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002;58:349-353.

Even though only subtle findings may distinguish VS and MCS patients at the bedside, a wide separation in underlying functional cerebral substrates associated with the two conditions is indicated by neuroimaging and electrophysiologic and pathologic studies.²⁰^–²³ Autopsy studies of patients with clinical histories consistent with MCS demonstrate reduced overall levels of cerebral cell death and, in some MCS patients, no evidence of significant thalamic cell loss or severe diffuse axonal injury—a pattern never observed in VS patients.²³ Neuroimaging studies generally show widespread preservation of distributed cerebral network activation in response to sensory stimuli, including passive language stimuli²⁰^,²⁴ and auditory¹⁵ and somatosensory stimuli.²¹ Electrophysiologic studies typically show recovery of a broad range of frequency content on the electroencephalogram and, in some MCS patients, preservation of high-level passive semantic processing of spoken language.²² Such large-scale integrative network responses that involve cortical association regions are not typically seen in VS patients. The presence of recruitable large-scale cerebral networks in some MCS patients suggests a potential substrate for further recovery in these patients. These observations probably underlie the rare, but verified cases of late recovery of spoken language in some severely brain-injured patients with clinical histories consistent with long-standing MCS.²⁵ In a recent single-subject study, one MCS patient who had demonstrated preserved passive language responses recovered spoken language and consistent verbal and gestural communication with bilateral electrical stimulation of the central thalamus.²⁶