Plum and posner’s diagnosis of stupor and coma fourth Edition series editor sid Gilman, md, frcp
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patients reach treatment, experienced centers worldwide generally report an overall mortal- ity among patients with altered consciousness of less than 1% (Table 9–7). The death rate climbs to approximately 5% in those with grade 3 to 4 coma. The mortality can be substantially higher when institutions treat only small num- bers of patients or lack experience or proper facilities. Adverse prognostic factors in depres- sant drug coma include an advanced age, the presence of complicating medical illnesses (es- pecially systemic infections, hepatic insuffi- ciency, and heart failure), and lengthy coma. Alkaline diuresis (for phenobarbital), hemodi- alysis, and charcoal hemoperfusion all have been reported to shorten coma and improve prognosis for patients with severe poisoning, especially from phenobarbital. Barring unex- pected complications, patients recovering from depressant drug poisoning suffer no residual brain damage even after prolonged coma last- ing 5 days or more. Rare exceptions to this rule occur in overdose patients who suffer aspira- tion pneumonia or cardiac arrest (e.g., during tracheal or gastric intubation). A small number of patients develop cutaneous pressure sores or pressure neuropathies from prolonged pe- riods of immobility during the period of im- mobile coma before the victim is found and brought to hospital; this may be particularly common with barbiturate overdoses. VEGETATIVE STATE The vegetative state (also called coma vigil or apallic state) denotes the recovery of a crude cycling of arousal states heralded by the ap- pearance of ‘‘eyes-open’’ periods in an unre- sponsive patient. 63 Very few patients remain in eyes-closed coma for more than 10 to 14 days; vegetative behavior usually replaces coma by that time. Patients in VS, like comatose patients, show no evidence of awareness of self or their environment, but do retain brainstem regula- tion of cardiopulmonary function and visceral autonomic regulation. The term persistent vegetative state is now commonly reserved for patients remaining in that state for at least 30 days (see ANA Committee on Ethical Affairs 1993). As indicated in the paragraphs below, there are no clear criteria for determining when PVS becomes permanent. One reason for the inability to predict per- manence early in the course of PVS is that patients usually have badly damaged cerebral hemispheres combined with a relatively in- tact brainstem. Such a combination during the early days of illness causes coma with relatively good brainstem function, a picture similar to patients with reversible cerebral injury. Since the publication of the third edition of Stupor and Coma, guidelines to aid con- struction of prognosis in VS have advanced greatly. 64–66
The Multisociety Task Force on PVS,
64,65 a joint commission composed of neu- rologists, neurosurgeons, and other specialists, organized a comprehensive review of outcomes of patients with prolonged VS using GOS cri- teria. Outcomes of 434 adult and 106 pediatric patients with TBI and 169 adult and 45 pedi- atric patients with nontraumatic etiologies were assessed. Figure 9–4 displays data from the TBI group for adults. For patients in VS for at least 1 month, 52% had recovered con- sciousness at 1 year postinjury (some 33% of the patients had recovered earlier than 3 months from the time of injury). If adult TBI patients remained in VS at 3 months, the percentage recovering consciousness at 1 year dropped to 35%, and to 16% for VS lasting at least 6 months. For pediatric patients with a TBI- induced VS for 1 month, 62% recovered con- sciousness at 1 year; if VS persisted for 3 months, this percentage dropped only to 56%, and to 32% for patients in VS for at least 6 Consciousness, Mechanisms Underlying Outcomes, and Ethical Considerations 357
Conscious Traumatic Injury (N = 434) Traumatic Injury (N = 106) Dead 1
80 60 40 20 0 3 6 12 Children Adults PVS
Conscious % of Patients Dead 1
80 60 40 20 0 3 6 Months after Injury 12 PVS
Nontraumatic Injury (N = 45) Conscious Dead 1
80 60 40 20 0 3 6 Months after Injury 12 PVS
Nontraumatic Injury (N = 169) Conscious Dead 1
80 60 40 20 0 3 6 12 PVS Figure 9–4. Outcome for patients in a persistent vegetative state after a traumatic or nontraumatic injury. See also Table 9–11. (From the Multisociety Task Force, 64 with permission.) Table 9–11. Prognosis of Vegetative State (VS) in Traumatic and Anoxic Brain Injury N Dead (%) CI (99%) VS (%)
CI (99%) Conscious (%) CI (99%) Independent (%) CI (99%) Age
TBI* ABI* TBI
ABI TBI
ABI TBI
ABI TBI
ABI VS at 1 Month Adults 434
169 33 53 15 32 52 15 24 4 Children 106
45 9 22 29 65 62 13 27 6 VS at 3 Months Adults
218 77 35 (27–43) 46 (31–61) 30 (22–38)
47 (32–62)
35 (27–44)
8 (2–19)
16 (10–22)
1 (0–4)
Children 50 31 14 (1–27)
3 (0–11)
30 (13–47)
94 (82–100)
56 (37–74)
3 (0–11)
32 (15–49)
0 VS at 6 Months Adults 123
50 32 (40–64) 28 (12–44)
52 (40–64)
72 (56–88)
16 (9–27)
0 4 (0–9) 0 Children
28 30 14 (30–78) 0 54 (30–78) 97 (89–100) 32 (12–58)
3 (0–11)
11 (0–26)
0 *TBI, traumatic brain injury; ABI, anoxic brain injury. Adapted from Jennet 66 and the Multisociety Task Force. 65 months. The outcome of ‘‘conscious’’ per se does not reflect level of disability. However, the Task Force review indicated that for adults, within the 52% of patients recovering con- sciousness after 1 month in VS, only 24% be- came independent by GOS criteria. This figure dropped to 16% for VS lasting 3 months and to only 4% if taken out to at least 6 months. Not surprisingly, nontraumatic VS carries a far less optimistic prognosis. Figure 9–4 shows comparison percentages for adult and pediatric patients with nontraumatic VS. For adult VS patients remaining in VS at 1 month, only 15% regained consciousness (with only 4% inde- pendent by GOS). These percentages worsened to 8% and 0% for patients remaining in a non- traumatic VS for 3 and 6 months, respectively. Based on these data, the Task Force paper suggested that VS after 12 months following TBI, or 3 months following an anoxic injury, should be considered essentially permanent. However, it is important to recognize that a small number of patients may recover from VS be- yond these time points. 67–69 Such late recovery past the cutoffs for permanent VS from both anoxic and traumatic etiologies has generally been to levels of severe disability, including the minimally conscious state. 66 Nevertheless, appli- cation of these statistics to individual cases can be risky, unless independent evidence of the mechanism of brain injury is available, as rare cases of late recovery continue to be reported. The uncertainty in prognosis in such cases highlights the need for better methods, such as direct measurements of cerebral function, to help identify cases where recovery is likely. Mortality is very high within the first year; approximately one-third of patients die. 64,65 If
year is low and some patients may continue to live for many years. 66 Plum and Schiff studied one patient who had remained in PVS for 25 years (see Figure 9–8). Most patients in VS die from infection of the pulmonary system or urinary tract. Clinical, Imaging, and Electrodiagnostic Correlates of Prognosis in the Vegetative State A few clinical signs or confirmatory tests, in- cluding those negative predictors for coma in general (as reviewed previously), help predict the prognosis of VS. As noted, abnormal SSEPs reliably indicate cortical damage and a high probability of remaining in VS following anoxic and traumatic brain injuries. However, normal evoked responses do not predict recovery. In a study of 124 patients in VS or MCS following TBI, three variables predicted recovery of abil- ity to follow commands: (1) initial score on the Disability Rating Scale (DRS), (2) rate of change on the DRS measure in the first 2 weeks of observation, and (3) the time of admission to a rehabilitation program following injury. 70 Several structural and functional correlates of VS have been examined. A prospective study of MRI imaging correlates of 80 patients re- maining in VS following TBI at 6 to 8 weeks (with MRI and clinical follow-up at 2, 3, 6, 9, and 12 months) found that 42 patients who remained in VS at 1 year showed that structural injuries within the corpus callosum and dorso- lateral brainstem significantly predicted nonre- covery (214-fold and sevenfold higher probabi- lity of nonrecovery from VS, respectively, based on adjusted odds ratios accounting for age, GCS, pupillary dysfunction, and number of brain lesions). 71 Overall, this model achieved a classification rate of 87.5% for identifying pa- tients who would not recover past VS. Quantitative fluorodeoxyglucose-positron emission tomography (FDG-PET) studies mea- suring resting cerebral metabolism have con- sistently demonstrated that global cerebral me- tabolism is markedly reduced to 40% to 50% of normal metabolic rates in most VS patients (see page 365). Unfortunately, early identification of low metabolic activity is not a clear predictor of outcome and some patients have recovered consciousness despite significant remaining ab- normalities in resting metabolic level. 72 The N-
acetylaspartate (NAA)-to-creatine (Cr) ratio on magnetic resonance spectroscopy (MRS) of the thalamus is low in all patients in VS, but lower in those who do not recover 73 ; however, only a few patients have been studied. Efforts to predict outcome or characterize VS using EEG have been disappointing. EEG studies may remain abnormal as patients im- prove or, conversely, improve when patients do not.
74 Event-related potentials (ERPs) may hold more promise. These potentials require cortical processing of stimuli that can be pas- sively presented to subjects in VS. The re- sponses are long latency with peak activation Consciousness, Mechanisms Underlying Outcomes, and Ethical Considerations 359
usually several hundred milliseconds after stim- ulation and are not strictly time locked to the stimulus onset. Long-latency auditory cortical potentials (N100, P150), the P300 response, and the mismatch negativity (MMN) ERPs have each shown some potential for providing evi- dence of recovery. The P300 response can be elicited by inclusion of an ‘‘oddball’’ tone in an otherwise monotonous presentation of re- peated identical tones. The MMN is an early component of the auditory response to the oddball stimulus that is attention independent and reliably induced following the N100 au- ditory cortex potential, an early primary audi- tory evoked response. In a study of 346 patients in coma for 12 months with outcomes divided into VS versus all categories better than VS (including MCS), N100 and MMN were strong predictors of recovery past VS; no patient with MMN in this cohort remained in VS. If the electrophysiologic variables were combined with information about the pupillary light re- flex, the probability of recovery past VS reached 89.9%. 40 However, other studies have raised questions about the specificity of pre- served ERP responses 75 in VS.
MINIMALLY CONSCIOUS STATE The minimally conscious state 76 identifies a condition of severely impaired consciousness with minimal but definite behavioral evidence of self or environmental awareness. Table 9–12 provides the criteria for the diagnosis of MCS. Like VS, MCS often exists as a transitional state arising during recovery from coma or during the worsening of progressive neurologic dis- ease. In some patients, however, it may be a permanent condition. A few studies have ex- amined differences in outcome between VS and MCS. Giacino and Kalmar reported ret- rospective findings in 55 VS patients and 49 MCS patients evaluated at 1, 3, 6, and 12 months following either traumatic or nontrau- matic injuries. 77 Both presented with similar levels of disability at 1 month postinjury. The MCS patients, however, had significantly bet- ter outcomes as measured by the Disability Rating Scale compared with outcomes for VS patients at 1 year, particularly in the TBI pa- tients. Strauss and colleagues 78 retrospectively studied life expectancy of a large number of children (ages 3 to 15) in VS (N ¼ 564) and MCS, dividing the latter into two groups: immobile MCS (N ¼ 705) and mobile MCS (3,806). A significant increase in the percent- age of patients still alive at 8 years was noted for the mobile MCS group (81%) compared to theimmobileMCS(65%)ortheVS(63%)group; the latter two were statistically indistinguish- able. Lammi and associates 79 examined 18 MCS patients 2 to 5 years after injury and found a marked heterogeneity of outcome despite prolonged duration of MCS after TBI. Most of their patients regained functional indepen- dence, but there was a poor correlation be- tween duration of MCS and outcome. In gen- eral, clinical and electrodiagnostic tests have not yet been developed for use in the diagnosis and prognosis of MCS outside of a research context (see below for discussion). MCS also includes some forms of the clini- cal syndrome of akinetic mutism (Box 9–1) and other less well-characterized disorders of con- sciousness. At least two different identifiable groups of patients are considered exemplars of akinetic mutism. Although occasionally con- fused with VS, classical akinetic mutism re- sembles a state of constant hypervigilance. The patients appear attentive and vigilant but Table 9–12 Aspen Working Group Criteria for the Clinical Diagnosis of the Minimally Conscious State Evidence of limited but clearly discernible self or environmental awareness on a reproducible or sustained basis, as demonstrated by one or more of the following behaviors: 1. Simple command following 2. Gestural or verbal ‘‘yes/no’’ responses (independent of accuracy) 3. Intelligible verbalization 4. Purposeful behavior including movements or affective behaviors in contingent relation to relevant stimuli. Examples include: a. Appropriate smiling or crying to relevant visual or linguistic stimuli b. Response to linguistic content of questions by vocalization or gesture c. Reaching for objects in appropriate direction and location d. Touching or holding objects by accommodating to size and shape e. Sustained visual fixation or tracking as response to moving stimuli From Giacino et al., 76 with permission. 360 Plum and Posner’s Diagnosis of Stupor and Coma Box 9–1 Akinetic Mutism Versus ‘‘Slow Syndrome’’ The term akinetic mutism originated with Cairns and colleagues. 80 They described a young woman who, although appearing wakeful, became mute and rigidly mo- tionless when a craniopharyngiomatous cyst expanded to compress the walls of her third ventricle and the posterior medial-ventral surface of the frontal lobe. The patient appeared to be unconscious; there was no spasticity. After the cyst was drained, she recovered full awareness but possessed no memory of the ‘‘uncon- scious’’ period. Eye movements were not described in this woman but most doc- umented cases of this type reveal seemingly attentive, conjugate eye movements. Oculocephalic stimulation may elicit some lateral gaze. Subsequent observations have shown that similar findings can be produced by lesions of the medial-basal prefrontal area, the anterior cingulate cortex, the medial prefrontal regions supplied by the anterior cerebral arteries, and the ros- tral basal ganglia. A similar syndrome can rarely be a feature of untreated, rigid Parkinson’s disease or prion disease. 81 The hyperattentive form of akinetic mutism is typically seen in patients with bilateral lesions of the anterior cingulate and medial prefrontal cortices, as oc- curs after rupture of an anterior communicating artery aneurysm. 82 The associated injury may sometimes be accompanied by injury to the hypothalamus and anterior pallidum. Castaigne and associates 83 and Segarra 84 introduced ‘‘akinetic mutism’’ to describe the behavior of patients suffering structural injuries affecting the medial-dorsal thalamus extending into the mesencephalic tegmentum. The pa- tients suffered severe memory loss and demonstrated apathetic behavior. Al- though such patients exhibit severe global disturbances of consciousness, they are not categorized as minimally conscious because they are capable of commu- nication. To mitigate confusion, we use the term slow syndrome 85 to describe pa- tients who appear apathetic and hypersomnolent but are able to move and may speak with understandable words. 86 Unlike akinetic mute patients, they are not semi-rigid and lack the appearance of vigilance. Subcortical lesions that may produce the slow syndrome include bilateral lesions of the paramedian anterior or posterior thalamus and basal forebrain; the mesencephalic reticular formation including periaqueductal gray matter, caudate nuclei (or either caudate in isola- tion), and globus pallidus interna; or selective interruption of the medial forebrain bundle.
A common denominator of akinetic mute states may be damage to the cortico- striato-pallidal-thalamocortical loops that are critical for the function of the frontal lobes. 87
ventral pallidum, and mediodorsal nucleus of the thalamus; akinetic mutism can result from bilateral damage at any level of this system. 87 Similarly, bilateral injury to the nigrostriatal bundle in the lateral hypothalamus may produce a state of akinetic mutism that is reversible with dopaminergic agonists. 88 At least partial cognitive function can be recovered following restricted bilateral injuries to the paramedian thalamus and mesencephalon. 83,84,89,90 361
remain motionless with robust preservation of visual tracking in the form of smooth pursuit movements (or optokinetic responses). Lim- ited preservation of brief visual fixation can be accepted in VS, but robust and consistent vi- sual tracking as seen in akinetic mutism is ab- sent in VS. 66 Patient 9–2 A 47-year-old right-handed man was brought to the ICU with progressive somnolence and unre- sponsiveness. Neurologic examination revealed bilateral third nerve palsy, fluctuating bradycardia with hypertension, and extensor posturing to pain. The initial CT scan (Figure 9–5A) revealed a large mass lesion centered on the mesencephalon with surrounding edema. Intracranial lymphoma was suspected and confirmed by biopsy. The patient received cranial irradiation, IV steroids, and che- motherapy. A posttreatment MRI (Figure 9–5B) demonstrated resolution of mass effect with high signal abnormalities within the upper mesenceph- alon and hypothalamus. The patient appeared alert but did not initiate communication. He occa- sionally displayed sudden periods of agitated be- havior. Responses to simple questions were mark- edly delayed, but correct using yes and no answers. Yüklə 9,02 Mb. Dostları ilə paylaş:
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