Brain Death and the
Vegetative State
Kurt A Jellinger, Institute of Clinical Neurobiology, Vienna, Austria
Based in part on the previous version of this Encyclopedia of Life Sciences
(ELS) article, Brain Death and the Vegetative State by Bryan Jennett.
A brain-dead patient is unconscious, has lost the capacity
to breathe (apnoea) and requires mechanical respiration;
even with full supportive treatment his heart will soon
stop, usually only after a few days. The widely accepted
definition of brain death (BD) equates it with death of a
person and renders legally the removal of organs for
transplantation. Evidence-based criteria for the clinical
diagnosis of BD and the use of confirmatory tests are
available. A patient in the vegetative state is unconscious
but has his eyes open and can breath on his or her own, but
requires artificial feeding, automatic-vegetative func-
tions and some active functions of the severely damaged
brain being preserved. Its diagnosis is based on repeated
clinical observations and modern neuroimaging tests.
Given adequate treatment persons in a vegetative state
can survive for years and may recover towards the min-
imally conscious state or even can regain (in)complete
recovery.
Introduction
Modern techniques of resuscitation and intensive care can
often rescue patients from acute brain damage resulting
from head injury, brain haemorrhage, cardiorespiratory
arrest and other life-threatening conditions. Some rescued
patients recover completely, but in others irrecoverable
brain damage has already occurred. The rescue procedures
may then only prolong the process of dying for hours or
days because the brainstem or other vitally essential brain
areas are dead, or they may leave the patient to survive for
ELS subject area: Neuroscience
How to cite:
Jellinger, Kurt A (April 2010) Brain Death and the
Vegetative State. In: Encyclopedia of Life Sciences (ELS). John Wiley &
Sons, Ltd: Chichester.
DOI: 10.1002/9780470015902.a0002212.pub2
ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Advanced article
. Introduction
Article Contents
. Brain Death
. Causes of Brain Death
. Criteria for Diagnosis
. The Vegetative State
. Management of the Vegetative State
Online posting date: 19th April 2010
months or years in a vegetative state (VS), because the
cerebral cortex, thalamus and the connecting neuronal
circuits are out of action. There are important distinctions
between these two kinds of brain damage: a brain-dead
patient has lost the capacity to breathe (apnoea) and
requires mechanical ventilation; even with full intensive
treatment his heart soon stops, usually after a few days, and
there are no reported cases of recovery from correctly
diagnosed brain death (BD). The patient in a VS can breath
on his/her own but requires articial feeding; given
adequate support he can survive for years and may even
recover (in)completely.
The death of the brain and permanent cessation of all
body functions show a dierent sequence; therefore, the
time of death of a person is still considered arbitrarily. In
biblical times death was usually recognised by the lack of
breathing; later the absence of heartbeat became the usual
signal of death. In 1968, the Harvard criteria equated
irreversible coma and apnoea (BD) with human death.
Since then, clinical studies have dened a spectrum of states
of impaired consciousness: coma, akinetic mutism, locked-
in syndrome, minimally conscious state (MCS), VS and BD
(Zeman, 2008; Bernat, 2008; Howard et al., 2009). Recent
denitions of death are the irreversible loss for the capacity
of consciousness combined with that to breath (Conference
of Medical Royal Colleges and their Faculties in the United
Kingdom, 1995), whereas the common law standard for
determining death is the cessation of all vital functions,
traditionally demonstrated by an absence of spontaneous
respiratory and cardiac functions. The Uniform Deter-
mination of Death Act (1990) stated that An individual
who has sustained either (1) irreversible cessation of cir-
culatory and respiratory functions, or (2) irreversible ces-
sation of all functions of the entire brain, including the
brainstem, is dead. It permitted organ procurement from
heart-beating donors and was approved by the American
Medical Association (1980) and by the American Bar
Association (1981). When cerebral lesions are irreversible
and death is declared, not all organs and their cells are dead
so that viable organs and tissues can be removed for
donation even after the heart has stopped.
There are several sequences by which the process of
death occurs. Often the heart fails rst and the lack of
oxygen delivery to the brain results rst in the cerebral
1
 Brain Death and the Vegetative State
cortex, the thalamus and then the brainstem ceasing to
function; without a functioning brainstem, breathing
stops. When breathing fails rst, from choking, strangling,
drowning or paralysis, the cortex and next the thalamus
and brainstem fail from oxygen lack, while the heart may
go on beating. In cases of injury, brain haemorrhage or
other lesions causing increased intracranial pressure, the
breathing stops due to brainstem damage, inducing irre-
versible damage to the cortex, while the heart still beats. If
the brainstem is primarily damaged due to trauma or
infarction, or as a result of prolonged oxygen lack, then
respiration will not return although the heart may beat for
days if ventilation is continued, but intracranial blood ow
stagnates and stops. This is BD. Resuscitation manoeuvres
may restart briey stopped heart, and articial ventilation
can take over the breathing. If the cause of the crisis is
temporary, recovery may occur, provided the rescue pro-
cedures were begun soon and were ecient enough to
prevent brain damage. A few minutes delay in resusci-
tation may enable the brainstem to survive and spon-
taneous breathing to return even though the most
vulnerable cortex and thalamus are irreversibly damaged,
resulting in VS.
Brain Death
BD is the expression for irreversible loss of brain function.
It is a precisely dened clinical diagnosis for which many
dierent criteria have been developed, but all are broadly
similar. It generally equates to functional death of the
brainstem, and when this has occurred, there is no possible
chance to recovery, since the downward signals main-
taining breathing and the upward signals activating the
cerebral cortex cease. BD is declared when brainstem
reexes, motor responses and respiratory drive are absent
in a normothermic, nondrugged comatose patient with a
known irreversible massive brain lesion and no contrib-
uting metabolic derangements. Total and permanent loss
of all brain functions is a medical and legal determina-
tion of death (http://www.organtransplants.org/glossary.
html). The spinal cord is unaected by intracranial catas-
trophes and is quite resistant to hypoxia. As a result reex
movements of the limbs depending only on spinal cord
function can persist after BD. One dramatic and poten-
tially distressing response is the Lazarus sign in which the
arms may elevate slowly and the trunk ex. None of these
spinal reexes indicate preservation of the brain, as
opposed to the spinal function.
Causes of Brain Death
The most common causes of BD are listed in Table 1.
About half the cases follow traumatic brain injury (TBI),
either with primary impact damage of the brainstem or
when respiratory or intracranial circulation failure occur
due to damage of the brainstem caused by cerebral oedema
2 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Table 1 Most common aetiologies of BD
Traumatic brain injury
Aneursymal subarachnoid haemorrhage
Intracerebral haemorrhage
Ischaemic stroke with cerebral oedema and herniation
Hypoxic-ischaemic encephalopathy (cardiorespiratory arrest,
etc.)
Hepatic failure with cerebral oedema and increased
intracranial pressure
or haemorrhage causing raised intracranial pressure.
About one-third of brain-dead patients have suered a
severe intracranial haemorrhage from a ruptured aneur-
ysm or blood vessel. The remaining cases are due to sys-
temic hypoxia from cardiac or respiratory arrest,
strangulation, drowning or other catastrophic events
associated with cerebral oedema and raised intracranial
pressure.
Criteria for Diagnosis
A reliable diagnosis can be made on clinical grounds pro-
vided there is strict adherence to guidelines such as those
proposed by the Conference of Medical Royal Colleges
and their Faculties in the United Kingdom in 1976 and
conrmed in 1995 (Table 2a) or the American Academy of
Neurology practical guidelines to determine BD (Quality
Standards Subcommittee of the American Academy of
Neurology, 1995). Detailed evidence-based guidelines and
practical parameters for the clinical diagnosis of BD are
available from the American Academy of Neurology
online (http://www.aan.com).
All observers agree that to conclude that the vital func-
tions of the brain have ceased, no behavioural or clinical
reex responses that depend on structures innervated from
the supraspinal nervous system can exist. Because fore-
brain functions depend on the integrity of the brainstem,
the examination primarily focuses on brainstem activity.
These observations may be accompanied by conrmatory
tests providing evidence of absence of cerebral hemispheric
and brainstem function (Table 2b).
When the clinical examination is unequivocal, no add-
itional conrmatory tests for the diagnosis of BD are
required. However, if there is any question, clinical prac-
tical guidelines suggest the potential use of several modal-
ities of conrmatory testing in the determination of
BD: angiography, electroencephalography (EEG)/evoked
potentials, transcranial Doppler sonography (TCD),
cerebral scintigraphy and magnetic resonance angiography
(MRA) (see Posner et al., 2007; Segura et al., 2009). A
survey of BD guidelines in 80 countries revealed uniform
agreement on the neurological examination with exception
of the apnoea test, the mandatory or optional use of con-
rming tests and dierences in the time of observation
(Wijdicks, 2002).
 Brain Death and the Vegetative State

Table 2a Criteria for diagnosis of BD in United Kingdom

All of the following should co-exist
. The patient must be deeply comatose. There should be no suspicion that this is due to CNS depressant drugs; primary
hypothermia must have been excluded and any metabolic or endocrine contribution or cause of coma carefully assessed.
. The patient must be maintained on a ventilator because spontaneous respiration has previously become inadequate or ceased
altogether. Neuromuscular blocking agents must have been excluded as a cause of respiratory failure. Failure of
neuromuscular transmission from other causes may need to be excluded by use of a nerve stimulator.
. There should be no doubt that the patients condition is due to irremediable structural brain damage and the diagnosis of the
underlying cause of BD should have been fully established.

Table 2b Clinical criteria for BD in the United States

Coma of established cause
. No potentially anaesthetising amounts of either toxins or therapeutic drugs can be present; hypothermia below 308C or other
physiologic abnormalities must be corrected to the extent medically possible.
. Irreversible structural disease or a known and irreversible endogenous metabolic cause due to organ failure must be present.
. Absence of motor responses.
. Absence of pupillary responses to light and pupils at midposition with respect to dilatation (4-mm).
. Absence of corneal reexes.
. Absence of the vestibulo-ocular reexes (after infusion of 20 mL of ice cold water into each external auditory meatus).
. Absence of gag reex.
. Absence of coughing in response to tracheal suctioning.
. Absence of sucking and rooting reexes.
. Absence of respiratory drive at a PaCO2 that is 60 or 20 mmHg above normal baseline values (apnoea test).
. Interval between two evaluations by patients age:
J term to 2 months old, 48 h

J 52 months to 1 year old, 24 h

J 1 year to518 years old, 12 h

J 418 years old, optional.

Neuropathology of brain death Safeguards to and pitfalls in the diagnosis

As in the majority of cases increased intracranial pressure
is the main mechanism of BD, and intracranial blood
ow stagnates and eventually stops, while maintenance of
heart action, haemodynamics and oxygenation can sup-
port somatic organs, neuropathologists have noted par-
ticular characteristics in supported brain-dead patients
and coined the term respirator brain (Walker et al.,
1975). Although areas of brain were preserved, neuronal
injury was generally extensive (hypoxemic panencepha-
lopathy). Using modern methods, a recent study of 41
patients who fullled the clinical criteria of BD and
terminal cardiac arrest showed profound neuronal
ischaemic changes in cortex and basal ganglia in 53
68%, with mild changes in a third of cerebral hemi-
spheres and in half of the brainstems, but total brain
necrosis was not found. As neuropathological ndings in
this series lacked sucient distinctive characteristics, the
diagnosis of BD should further be based on clinical
assessment alone (Wijdicks and Pfeifer, 2008).
of brain death
The problem has assumed considerable importance in
recent years, rst because of the increasing diculty in
deciding whether it is justiable to maintain life inde-
pendently with articial support in patients with severe
brain damage and second because of the dicult question
of deciding when a cerebral lesion is irreversible and death
is imminent, so that viable organs for donation may be
removed. It is now widely accepted that BD denotes death
of the individual and is a generally accepted legal denition
that rests on two assumptions: if the brainstem is dead then
the brain is dead in terms of integrated function, and when
the brain is dead the person is dead. The rst notion to
adopt BD as a legal denition was the U.S. state of Kansas
in 1970 and the rst European country Finland in 1971.
Since then laws on determining death have been imple-
mented in all countries with active organ transplantation
programs (Randell, 2004; Escudero et al., 2009; Jousset
et al., 2009).

ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net 3
 Brain Death and the Vegetative State
Despite the adoption of whole BD criteria in the United
States and brainstem criteria in the United Kingdom,
stating that death can be declared when the diagnosis of
BD is conrmed and not at some later time when the heart
stops (Conference of Medical Royal Colleges and their
Faculties in the United Kingdom, 1979), there has been
opposition to BD criteria. A recent paper argues against the
validity of the Harvard criteria for equating BD with
human death based on both medical and legal criteria
emphasising that society must decide if physician-assisted
death is permissible and desirable with regard to end-of-life
organ donation (Verheijde et al., 2009). For contemporary
controversies in the denition of death see Bernat (2009b),
Evans (2009), Joe (2009) and Controversies in the
Determination of Death (2008).
According to the 1998 code of practice (United Kingdom
Health Departments, 1998), the time of death is when the
rst set of tests indicates brainstem death. This removes any
ambiguity about the action of doctors who discontinue
ventilation after diagnosing BD. They do not withdraw
support to allow someone to die, but stop an intervention
that is inappropriate when a patient is already dead.
The concern was that anxieties to secure organs might
lead to premature diagnosis of BD, and therefore, the
Department of Health in the United Kingdom published
a code of practice in 1998, which was updated in 2008.
However, one must be aware of the sensitivity of the rela-
tives and professional carers of brain-dead patients, and of
the public in general in this issue. Therefore, it is essential to
ensure that the diagnosis is always established beyond
doubt. This depends largely on evidence-based and
nationally agreed consensus criteria, and on requiring that
the nal conrmatory tests are carried out on two separate
occasions and involve two adequately experienced phy-
sicians (not agreed in all countries), whose ndings are
documented in the records. The cornerstones of the diag-
nosis remain a careful and sure clinical examination. Per-
haps the best safeguard is to allow sucient time after the
brain insult before declaring BD: at least 6 h, but 1224 h is
more usual, and occasionally up to 36 h are mandatory.
Observation time can be shortened if one conrmatory test
is positive for BD (Wijdicks, 2002).
Potential pitfalls in the diagnosis of BD may occur in
chronically ill patients and in those with clinical and elec-
trocardiographic cardiac arrest who, after failed attempts
at resuscitation, were declared dead, only to be discovered
to be alive later, sometimes in the mortuary. Some of these
pitfalls are outlined in Table 3.
In patients with very deep but reversible anaesthesia due
to sedative drug ingestion, which results in the clinical
appearance of BD, and even an electrically silent EEG, the
combination of a prolonged period of observation (more
than 24 h), loss of cerebral perfusion and exclusion of other
potential confounds is required (Quality Standards Sub-
committee of the American Academy of Neurology, 1995).
In the United Kingdom, brainstem death renders legal
the removal of organs for transplantation, provided that
appropriate consent has been obtained. It is generally
4 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
Table 3 Some pitfalls in the diagnosis of BD
Findings Possible causes
Pupils xed Anticholinergic drugs, tricyclic
antidepressants, neuromuscular
blockers
No oculovestibular Ototoxic agents, vestibular
reexes suppression, preexisting disease,
basal skull fracture
No respiration Posthyperventilation apnoea,
neuromuscular blockers
No motor activity Neuromuscular blockers, locked-in
syndrome, sedative drugs
Isoelectric EEG Sedative drugs, anoxia,
hypothermia, encephalitis, trauma
Source: Reproduced from Posner et al. (2007), with permission from
Oxford University Press.
followed by cardiac death within hours to weeks, although
there are reported exceptions to this rule. If the permission
has been given for a removal of organs for transplantation,
there may be a need to continue ventilation and other
supportive treatment to maintain organs in optimal con-
dition for transplantation. Only a proportion of brain-
dead patients are suitable to be organ donors, and it is
important to emphasise that even when transplantation is
not the issue, it is still good practice to discontinue venti-
lation once the diagnosis of BD is conrmed. Not to do so
needlessly prolongs the distress of relatives, deprives the
patient of death with dignity, is bad for the morals of the
nursing sta and is an inappropriate use of expensive
intensive care resources.
The Vegetative State
Definition and diagnosis
The VS rst dened by Jennett and Plum (1976), also called
coma vigile or apallic state, consists of continuing uncon-
sciousness with no evidence of awareness, accompanied by
sleepwake cycles, periods of wakefulness with the eyes
open, reacting pupils and spontaneous breathing. A wide
repertoire of brainstem automatic functions or reex
activity is preserved, yawning occurs, but there is bladder
and bowel incontinence. The patients may be aroused by
painful or salient stimuli, which may provoke facial grim-
acing or a groan, but show no signs of discriminative per-
ception or deliberate action, and no evidence of language
comprehension or expression. The head and eyes may turn
towards a loud noise and there may be smiling unrelated to
any appropriate stimulus. Some reex swallowing may
occur, but adequate nutrition and hydration depends on
tube feeding, either through the nose or through a tube
placed into the stomach. There is dissociated cerebral
dysfunction with total loss of associative and cognitive
 Brain Death and the Vegetative State

abilities but maintenance of autonomic-vegetative controls Nature of the brain damage

(Bernat, 2006, 2009a; Jennett, 2005; Zeman, 2008).
The persistent VS (PVS) has been dened as one that is
present 1 month after traumatic or nontraumatic brain
injury and lasting for at least 1 month in patients with
degenerative and metabolic disorders or developmental
malformations (Multi-Society Task Force on PVS, 1994;
Posner et al., 2007). Others have dened it as a clinical
condition of unawareness of self and environment in which
the patient breathes spontaneously, has a stable circu-
lation, and shows cycles of eye closure and opening which
may simulate sleep and waking (Royal College of Phys-
icians, 2003). Continuing VS was suggested to continue
more than 4 weeks, while the PVS is considered as diagnosis
when it follows a brain trauma for more than 3 months
(Multi-Society Task Force on PVS, 1994) or other causes of
brain damage for more than 6 months (United Kingdom
Health Departments, 1998). There is increasing use of the
term vegetative state rather than persistent or permanent
vegetative state.
The VS demands considerable skill for diagnosis and
requires reassessment over a period of time to ensure that
there is no purposeful response to external stimuli. The
diagnosis may be supported by EEG showing slow-wave
activity and functional imaging studies showing a con-
siderable drop of cerebral metabolism to below 50% of the
normal range (Posner et al., 2007). In VS patients, external
stimuli activate primary cortices but not higher-order
association areas from which they are disconnected
(Laureys, 2004; Laureys et al., 2000, 2004).
Despite the importance of diagnostic accuracy, the role
of misdiagnosis of VS has not substantially changed in the
past 15 years; standardised neurobehavioural assessment is
necessary (Schnakers et al., 2009). For routine use, brain
imaging is helpful to aid the clinical diagnosis of disorders
of consciousness (Coleman et al., 2009).
(neuropathology)
Post-mortem examination of brains of patients who have
died in the VS shows a variety of morphological lesions at
various levels from the cerebral cortex and white matter via
the basal ganglia to the upper and lower brainstem; they
may be accompanied or superimposed by other (second-
ary) morphological lesions in the central and peripheral
nervous system. The three main types in brain damage
include widespread damage to the grey matter, diuse
white matter lesions and damage to the thalami, upper and
lower brainstem. The major types and lesion patterns are
shown in Figure 1.
Following cardiorespiratory arrest or other hypoxic
episodes, there is diuse or multifocal loss of neurons in the
cerebral cortex (laminar necrosis) and hippocampus,
although occasionally the main damage involves the tha-
lamus (Kinney and Samuels, 1994). In addition to hyp-
oxicischaemic lesions of the grey matter, diuse
demyelination of the hemispheral white matter may occur.
After head injury most cases have diuse axonal injury
aecting the cerebral hemispheres causing secondary
(a) (b)

Causes
(c) (d)
The VS follows various types of severe acute and pro-
gressive brain damage; about half of the patients had a
severe head injury. Nontraumatic causes are mostly events
of systemic hypoxia, such as cardiac arrest or respiratory
obstruction, results of a medical accident or other intra-
cranial catastrophes. Apart from acute insults, the VS can
(e) (f)
evolve gradually in end states of chronically neurodegen-
erative or dementing disorders, such as Alzheimer or
Huntington disease, in toxic, metabolic or inammatory
diseases (diuse sclerosis, prion diseases, etc.). In children it
can result from severe congenital malformation of the
brain or from progressive metabolic or chromosomal dis-
eases (amaurotic idiocy, leukodystrophy). Less frequent (g) (h)
causes are tumours of the rostral brainstem, whereas
lesions (infarcts) of the ventral brainstem cause the locked- Figure 1 Cerebral lesion patterns in disorders of consciousness. (a) Diffuse
in-syndrome (cerebromedullar disconnection syndrome) lesion of the cerebral cortex (laminar necrosis). (b) Diffuse damage to the
hemispheral white matter. (c) and (d) Lesions of the upper brainstem
abolishing the descendent control of voluntary movement. involving the ascending reticular system. (e) Lesions of the limbic system.
In this syndrome, patients are capable of communicating (f) Lesions of the pontine basis (locked-in-syndrome). (g) Multiple cerebral
using only movements of the eyes or eyelids. lesions in various locations. (h) Diffuse anoxic panencephalopathy in BD.

ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net 5
 Brain Death and the Vegetative State

degeneration of thalami and long descending bre tracts.
They may be associated with cerebral haemorrhages and
lesions to the corpus callosum and other brain areas.
Although the cortices may be intact, their connections to
the rest of the brain and nervous system have been lost. In
patients surviving between 1 month and 8 years following
blunt head trauma, diuse axonal injury was observed in
71% and thalamic lesions in 80% and in 96% of those
surviving more than 3 months, with additional ischaemic
brain damage in 43% due to a global reduction of cerebral
blood ow (Adams et al., 2000; Jennett et al., 2001). There
may be overlap of primary (traumatic) and secondary
(post-traumatic) brain lesions (Blumbergs et al., 2008).
Similar lesions, but less severe and extensive, are found in
patients who have recovered to very severe disability.
Essential factors for the course and prognosis of the VS
are the pattern and extent of the lesions in the brainstem.
Although centrally located lesions in the brainstem teg-
mentum and periaquaeductal-reticular areas hardly allow
any remission, more peripherally located lesions in the
posterolateral brainstem are often associated with pro-
gressive remission.
Prognosis
There is discussion about the criteria for determining when
the VS becomes permanent, and some authors have dis-
agreed with the concept of PVS as some exceptional cases
have recovered some awareness after the time intervals
proposed by the Multi-Society Task Force on PVS.
A study of the outcomes of over 700 patients in the VS 1
month after the acute insult found that 52% from the TBI
group regained consciousness at 1 year post injury; if adult
TBI patients remained in VS at 3 months, the percentage
recovering consciousness at 1 year dropped to 35%, but
only 24% and 16%, respectively, became independent.
Nontraumatic VS carries a far less optimistic prognosis,
only 15% of those in VS at 1 month regained conscious-
ness, with only 4% independent; this worsened to 8% and
0% in a nontraumatic VS for 3 and 6 months, respectively
(Multi-Society Task Force on PVS, 1994). Many who
recover consciousness remain severely disabled and
dependent, particularly if they had remained vegetative for
6 months and more. Some recover to an MCS, the key
feature of which is that, although patients may be poorly
responsive, there is evidence of awareness, for example
following simple commands, gestural or verbal responses
to yes/no questions, reaching for objects and response to
sustained stimuli but not to neutral stimuli (Table 4) (Gia-
cino, 2005). The neuropathology in the MCS is generally
less severe than that seen in the VS with less thalamic
involvement or less diuse traumatic axonal injury. The
MCS may be the end point of recovery from the VS or a
transitional state before deterioration to a VS or death
(Figure 2).
Cortical activation studies using various stimuli in VS
and MCS patients have shown activation of secondary
association areas in addition to primary sensory areas
(Boly et al., 2004, 2008) and more so in patients in the MCS
(Owen et al., 2006). These may be objective evidence of a
potential pain perception capacity in patients with MCS
and less in VS, which supports the idea that these patients
need analgesic treatment (Boly et al., 2008). These data,
although indicating a widespread functional disconnection
across cortical pathways, suggest persistence of some active
functions even in these severely damaged brains (Schnakers
et al., 2008). They indicate a tendency towards recovery
with a specicity of 93% and a sensitivity of 69% (Di et al.,
2008). Recent PET studies of regional cerebral blood ow
(rCBF) showed hypermetabolism in the ascending reticular
acticating system (ARAS) and impaired connectivity
between the ARAS and the precuneus, emphasising
the functional link between cortices and brainstem in the
genesis of perceptual awareness. This strengthens the
notion that consciousness is based on a widespread neuro-
nal network (Silva et al., 2010) that is default in non-
communicative brain-damaged patients (Vanhaudenhuyse
et al., 2010). The ethic role of imaging methods in the
prognosis of these disorders has been discussed (Fins et al.,
2008). See also: Consciousness: Mechanisms
There is high mortality rate within the rst year
approximately one-third of patients die. If patients remain
alive after a year, mortality is low, and some patients may
continue to live many years if given good care (Figure 3).

Table 4 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:
. Simple command following
. Gestural or verbal yes/no response
. Intelligible verbalisation
. Purposeful behaviour including movements or aective behaviours in contingent relation to relevant stimuli, for example:
(a) Appropriate smiling or crying to relevant visual or linguistic stimuli
(b) Response to linguistic content of questions by vocalisation 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 xation or tracking as response to moving stimuli
Source: Adapted from Giacino (2005), with permission from Elsevier.

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 Brain Death and the Vegetative State

Total
functional loss Cognitive function Normal

Functional Severe
communication
to Full Motor
moderate cognitive function
cognitive recovery
disability
(Persistent) Minimally
vegetative conscious
state state

Locked-in
Coma
syndrome Total
functional
loss

Figure 2 Conceptual overview of functional outcomes following severe brain injuries. Grey zone between vegetative state (VS) and minimally conscious
state (MCS) reflects rare patients with fragments of behaviour that arise spontaneously and not in response to stimulation. By nosologic criteria, these
patients remain in VS. The bold black line indicates emergence from the MCS, defined by reliable functional communication. Locked-in syndrome is not a
disorder of consciousness. Reproduced from Posner et al. (2007), with permission from Oxford University Press.

Traumatic injury Nontraumatic injury

Adults
100
Conscious
80 Conscious
% of patients

Dead
60

40 Dead

20 PVS
N=434 PVS N=169
0
1 3 6 12 1 3 6 12

Children
100
Conscious
80
Dead
% of patients

Conscious
60

40 Dead
PVS
20 PVS
N=106 N=45
0
1 3 6 12 1 3 6 12
Months after injury Months after injury

Figure 3 Outcome for patients in a persistent vegetative state (PVS) after traumatic or nontraumatic injury. Reproduced from Posner et al. (2007), with
permission from Oxford University Press.

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 Brain Death and the Vegetative State
Survival up to 25 years is not uncommon, and as long as
40 years have been reported. Most patients in VS die from
infection of the pulmonary system or urinary tract.
Management of the Vegetative State
There has been and still is much discussion of the VS in the
medical community as well as in the public whether it is
justiable to maintain life with articial support in patients
with severe brain damage (e.g. Karen Ann Quinlan contro-
versy in 1976; Theresa Schiavos tragedy in 2005; Bernat,
2008) and repeated debates in Catholic and other medical
ethics (see Wikipedia, Brain Death, June 2009). There is now
consensus in many countries that survival for years in a PVS
is of no benet to the patient, and that it is therefore
appropriate to withdraw life-sustaining treatment once
permanence is declared. In the USA many cases went to
court to seek support for discontinuing articial nutrition
and hydration. Although in the late 1980s judges of the U.S.
Supreme Court declared that these cases need no longer
come to court, this was repeatedly performed in the Schiavo
case. Since 1992 several cases have also gone to court in the
United Kingdom, including one to the House of Lords. All
these courts have maintained that articial nutrition and
hydration is medical treatment, and that like any other treat-
ment it can therefore be withdrawn if judged to be of no
benet to the patient. Only in the United Kingdom is it a
legal requirement to seek approval before withdrawing
treatment, although this situation is under review. Another
sensational case recently occurred in Italy. Once articial
nutrition and hydration are withdrawn, a peaceful death
occurs in 810 days; the cause of death is regarded as the
original brain damage. Although only a small minority of
families seek such treatment withdrawal, many agree to a
policy of no resuscitation and no new therapeutic inter-
ventions for life-threatening complications, such as
infection.
Scientific and social concerns
With regard to the attitude of science and society to con-
sciousness in BD and VS, one should consider that the
concept of BD has evolved as technology has progressed.
This has forced medicine and society to redene their
ancient cardiorespiratory-centred diagnosis to a neuro-
centric diagnosis of death (Bernat et al., 2010). The current
consensus about the denition of death has not yet
appeased all controversy, and ethical, moral and religious
concerns continue to present a malaise about the possible
expansion of the denition of death (Laureys, 2005;
Bruzzone, 2008), although, since the Harvard criteria have
been published, to the best of our knowledge, no patient
showing denite criteria of BD ever regained conscious-
ness. However, it appears debatable to incorporate the VS
into the denition of death, and there are major concerns
about the feared bias of formulating new criteria to facili-
tate organ transplantation.
8 ENCYCLOPEDIA OF LIFE SCIENCES & 2010, John Wiley & Sons, Ltd. www.els.net
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