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The Vegetative State Martin M Monti,1 Steven Laureys,2 Adrian M Owen1

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The Vegetative State Martin M Monti,1 Steven Laureys,2 Adrian M Owen1 CLINICAL REVIEW For the full versions of these articles see bmj.com The vegetative state Martin M Monti,1 Steven Laureys,2 Adrian M Owen1 1MRC Cognition and Brain Sciences The vegetative state may develop suddenly (as a conse- Unit, Cambridge CB2 7EF quence of traumatic or non-traumatic brain injury, such SOURCES AND SELECTION CRITERIA 2 Coma Science Group, Cyclotron as hypoxia or anoxia; infection; or haemorrhage) or gradu- This paper is largely based on a personal database of Research Center and Neurology articles from all three authors, including the most recent Department, Université de Liège, ally (in the course of a neurodegenerative disorder, such published work in primary research journals as well as Bât B30 Allée du 6 août no 8, as Alzheimer’s disease). Although uncommon, the condi- recent and influential reviews and chapters on the subject. B-4000 Liège, Belgium tion is perplexing because there is an apparent dissocia- Correspondence to: M M Monti We also searched PubMed using the keyword “vegetative [email protected] tion between the two cardinal elements of consciousness: ! state” and the limits “classical article, review and meta- awareness and wakefulness. Patients in a vegetative state analysis” Cite this as: BMJ 2010;341:c3765 appear to be awake but lack any sign of awareness of them- doi: 10.1136/bmj.c3765 selves or their environment.w! Large retrospective clinical audits have shown that as many as "#% of patients with a What is the vegetative state and what is it not? diagnosis of vegetative state may in fact retain some level The $##% guidance from the UK’s Royal College of Physi- of consciousness. Misdiagnosis has many implications for cians on diagnosing and managing the permanent vegeta- a patient’s care—such as day to day management, access tive state defines it as “a clinical condition of unawareness to early interventions, and quality of life—and has ethical of self and environment in which the patient breathes and legal ramifications pertaining to decisions on the dis- spontaneously, has a stable circulation, and shows cycles continuation of life supporting therapies.$ w$-w" of eye closure and opening which may simulate sleep and Overall, our understanding of the vegetative state is waking.”% Three main clinical features define the vegeta- incomplete. Although we know quite a lot about the neu- tive state: (a) cycles of eye opening and closing, giving the ropathology underlying the vegetative state, our ability to appearance of sleep-wake cycles (whether the presence of assess (un)consciousness and cognitive function in the eye opening and closing cycles actually reflects the pres- clinic is extremely limited, as highlighted by the high rate ence of circadian rhythms is unclearw& w'); (b) complete of misdiagnosis. lack of awareness of the self or the environment; and (c) complete or partial preservation of hypothalamic and SUMMARY POINTS brain stem autonomic functions.% " The guidelines from The vegetative state is a complex neurological condition the Royal College of Physicians consider a vegetative state in which patients appear to be awake but show no sign of to be persistent when it lasts longer than a month and awareness of themselves or their environment permanent when it lasts longer than six months for non- bmj.com archive Current clinical methods of diagnosis are limited in scope, traumatic brain injuries and one year for traumatic brain evidenced by a high rate (about 40%) of misdiagnosis injuries.% Guidelines published in the United States, how- Previous articles in this (that is, patients who are aware are considered to be ever, consider that for non-traumatic brain injury a per- series unconscious) manent vegetative state exists after only three months." ! Management of The main causes of misdiagnosis are associated with Although both the persistent and the permanent veg- alopecia areata a patient’s disability (such as blindness), confusion in etative states are often abbreviated to “PVS,” authors of (BMJ 2010;341:c3671) terminology, and lack of experience of this relatively rare condition a letter in the BMJ in $### suggested that to avoid con- ! Investigation and Furthermore, standard behavioural assessments cannot fusion the abbreviation should be used exclusively to management of distinguish an aware (that is, minimally conscious) but indicate a permanent vegetative state.w) The American congestive heart failure completely immobile patient from a non-aware patient Congress of Rehabilitation Medicine suggested that the (BMJ 2010;341:c3657) (one with vegetative state) cause of injury (traumatic, anoxic) as well as the time ! Obstetric anal In such behaviourally non-responsive patients, functional elapsed since onset of the condition should be docu- sphincter injury neuroimaging methods (such as magnetic resonance mented, as both are important for prognosis.w* (BMJ 2010;341:c3414) imaging or electroencephalography) can detect residual Experts have suggested that the vegetative state should cognition and awareness and can even establish two way be seen as part of a continuous spectrum of conditions, ! Perioperative acute communication, without requiring any behavioural output kidney injury from patients often referred to as disorders of consciousness, in which (BMJ 2010;341:c3365) Current guidelines should therefore be modified to include someone’s wakefulness and/or awareness are impaired & ' ! Huntington’s disease functional neuroimaging as an independent source of after severe brain injury (figure, table !). This sugges- (BMJ 2010;340:c3109) diagnostically relevant information tion is consistent with the idea that awareness and una- wareness are part of a continuum, and it highlights the 292 BMJ | 7 AUGUST 2010 | VOLUME 341 CLINICAL REVIEW disorder of consciousness, may be confused with veg- Acute brain injury etative state. Patients with locked-in syndrome are both awake and aware, yet they are entirely unable to produce Coma any motor output or they have an extremely limited rep- ertoire of behaviours (usually vertical eye movement or blinking).w!# w!! Locked-in Vegetative Chronic coma Brain syndrome state (very rare) death What causes the vegetative state? In terms of neuropathology, the vegetative state is mostly Minimally conscious state Permanent vegetative state marked by cortical or white matter and thalamic, rather (>3 months if non-traumatic, >1 year if traumatic) than brain stem, injury. A review of the evidence avail- Confusional state able up until !,," highlighted the fact that traumatic injury was found to be associated with diffuse damage to Increasing independence Death subcortical white matter (or diffuse axonal injury). Cases of non-traumatic injury, on the other hand, were found Flow chart of cerebral insult and coma. to have extensive necrosis in the cerebral cortex, almost w9 Adapted from Laureys et al, 2004 always associated with thalamic damage.!# In a more recent survey of patients with brain injury Table 1 | Consciousness and motor behaviour characteristics (n=",), %& ()!%) patients had traumatic brain injury, of in patients with disorders of consciousness and locked-in syndrome whom $& ()!%) had severe diffuse axonal injury and ) !! Consciousness ($#%) had major injury to the cerebral cortex. Among Sleep-wake Motor behaviour the %& patients, the thalamus seemed to be abnormal in Condition cycles Awareness characteristics $* (*#%) and damage to the brain stem was present in Coma No No No purposeful behaviour only & (!"%). In the !" ($,%) patients with non-trau- Vegetative state Yes No No purposeful behaviour matic injury, , ('"%) cases presented with diffuse neo- cortical damage; in all !" cases a profound and diffuse Minimally Yes Partial, Inconsistent but conscious state fluctuating reproducible purposeful neuronal loss was apparent in the thalamus and hippo- behaviour campus. Overall, these lesions effectively render a struc- Locked-in Yes Yes Yes, but limited to eye turally intact cortex unable to function by destroying the syndrome movements (depending connections between cortical areas via the thalamus, as on lesion) well as afferent and efferent cerebral connections. importance of differentiating the vegetative state from What affects prognosis in patients with a diagnosis of other related neurological conditions that may also fol- vegetative state? low catastrophic brain injury. Three major factors affect the prognosis of patients with vegetative state: time spent in the vegetative state, age, Coma and type of brain injury. Coma is a condition of unresponsiveness in which patients lie with their eyes closed, do not respond to Time spent in the vegetative state attempts to arouse them, and show no evidence of aware- A study of !"# patients showed that time spent in a veg- ness of self or of their surroundings.) Patients lack not etative state is negatively correlated with the chances of only signs of awareness (similar to vegetative state) but recovering independence and consciousness and posi- also wakefulness (unlike vegetative state) regardless of tively correlated with the probability of remaining in a how intensely they are stimulated. Patients typically vegetative state.!$ The role of time in prognosis was con- either recover or progress to a vegetative state (that is, firmed by a large review of '#% adult published cases,!% they show signs of wakefulness) within four weeks.% Irre- from which it was estimated that the chance of regaining versible coma with absent brainstem reflexes indicates independence at one year after injury steadily decreased
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