A
persistent vegetative state is a disorder of consciousness in which patients with severe
brain damage"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
are in a state of partial
arousalArousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...
rather than true awareness. It is a diagnosis of some uncertainty in that it deals with a
syndromeIn medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
. After four weeks in a
vegetative state (VS), the patient is classified as in a persistent vegetative state. This diagnosis is classified as a
permanent vegetative state (PVS) after approximately 1 year of being in a persistent vegetative state.
Medical definition
A wakeful unconscious state that lasts longer than a few weeks is referred to as a persistent vegetative state.
Lack of legal clarity
As opposed to
brain deathBrain death is the irreversible end of all brain activity due to total necrosis of the cerebral neurons following loss of brain oxygenation. It should not be confused with a persistent vegetative state...
, persistent vegetative state (PVS) is not recognized by
statute as
deathDeath is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
in any legal system. In the US and UK, courts have required petitions before termination of life support that demonstrate that any recovery of cognitive functions above a vegetative state is assessed as impossible by authoritative medical opinion.
This legal grey area has led to vocal advocates that those in PVS should be
allowed to dieThe right to die is the ethical or institutional entitlement of the individual to commit suicide or to undergo voluntary euthanasia. Possession of this right is often understood to mean that a person with a terminal illness should be allowed to commit suicide or assisted suicide or to decline...
. Others are equally determined that, if recovery is at all possible, care should continue. The existence of a small number of diagnosed PVS cases that have eventually resulted in improvement makes defining recovery as "impossible" particularly difficult in a legal sense. This legal and ethical issue raises questions about autonomy, quality of life, appropriate use of resources, the wishes of family members, and professional responsibilities.
History
The syndrome was first described in 1940 by
Ernst KretschmerErnst Kretschmer Prof. Dr. med. Dr. phil. h.c., was a German psychiatrist who researched the human constitution and established a typology...
who called it
apallic syndrome. The term
persistent vegetative state was coined in 1972 by
ScottishScotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
spinalIn human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
surgeonIn medicine, a surgeon is a specialist in surgery. Surgery is a broad category of invasive medical treatment that involves the cutting of a body, whether human or animal, for a specific reason such as the removal of diseased tissue or to repair a tear or breakage...
Bryan JennettBryan Jennett was a pioneering Professor of Neurosurgery who established Glasgow as a world centre in the speciality and made major advances in the care and management of patients...
and
AmericanThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
neurologistA neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
Fred PlumFred Plum was an American neurologist who developed the terms"persistent vegetative state" and "locked-in syndrome" as part of his continuing research on consciousness and comas and care of the comatose....
to describe a syndrome that seemed to have been made possible by
medicineMedicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
's increased capacities to keep patients' bodies alive.
Classification
There are several definitions that vary by technical versus laymen's usage, and by legal implications in different countries.
The vegetative state is a chronic or long-term condition. This condition differs from a
comaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
: a coma is a state that lacks both awareness and wakefulness. Patients in a vegetative state may have awoken from a coma, but still have not regained awareness. In the vegetative state patients can open their eyelids occasionally and demonstrate sleep-wake cycles, but completely lack cognitive function. The vegetative state is also called a "coma vigil". The chances of regaining awareness diminish considerably as the time spent in the vegetative state increases.
The persistent vegetative state is the standard usage (except in the UK) for a medical diagnosis, made after numerous neurological and other tests, that due to extensive and irrevocable brain damage a patient is
highly unlikely ever to achieve higher functions above a vegetative state. This diagnosis does not mean that a doctor has diagnosed improvement as impossible, but does open the possibility, in the US, for a judicial request to end life support. Informal guidelines hold that this diagnosis can be made after four weeks in a vegetative state. US caselaw
has shown that successful petitions for termination have been made after a diagnosis of a persistent vegetative state, although in some cases, such as that of
Terri SchiavoThe Terri Schiavo case was a legal battle in the United States between the legal guardians and the parents of Teresa Marie "Terri" Schiavo that lasted from 1998 to 2005...
, such rulings have generated widespread controversy,
In the UK, the persistent vegetative state is discouraged in favor of two more precisely defined terms that have been strongly recommended by the
Royal College of Physicians (RCP)The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...
. These guidelines recommend using a
continuous vegetative state for patients in a vegetative state for more than four weeks. A medical definition of a
permanent vegetative state can be made if, after exhaustive testing and a customary 12 months of observation, a medical diagnosis that it is
impossible by any informed medical expectations that the mental condition will ever improve. Hence, a "continuous vegetative state" in the UK may remain the diagnosis in cases that would be called "persistent" in the US or elsewhere.
While the actual testing criteria for a diagnosis of "permanent" in the UK are quite similar to the criteria for a diagnosis of "persistent" in the US, the semantic difference imparts in the UK a
legal presumption that is commonly used in court applications for ending life support. The UK diagnosis is generally only made after 12 months of observing a static vegetative state. A diagnosis of a persistent vegetative state in the US usually still requires a petitioner to prove in court that recovery is impossible by informed medical opinion, while in the UK the "permanent" diagnosis already gives the petitioner this presumption and may make the legal process less time-consuming.
Note that in common usage, the "permanent" and "persistent" definitions are sometimes conflated and used interchangeably. However, the initialism "PVS" is intended to define a "persistent vegetative state", without necessarily the connotations of permanence, and is used as such throughout this article.
Bryan JennettBryan Jennett was a pioneering Professor of Neurosurgery who established Glasgow as a world centre in the speciality and made major advances in the care and management of patients...
, who originally coined the term "persistent vegetative state", has now recommended using the UK division between continuous and permanent in his most recent book
The Vegetative State. This is one for purposes of precision, on the grounds that "the 'persistent' component of this term ... may seem to suggest irreversibility".
The Australian National Health and Medical Research Council has suggested "post coma unresponsiveness" as an alternative term for "vegetative state" in general.
Signs and symptoms
Most PVS patients are unresponsive to external stimuli and their conditions are associated with different levels of consciousness. Some level of consciousness means a person can still respond, in varying degrees, to stimulation. A person in a coma, however, cannot. In addition, PVS patients often open their eyes in response to feeding, which has to be done by others; they are capable of swallowing, whereas patients in a coma subsist with their eyes closed (Emmett, 1989).
PVS patients' eyes might be in a relatively fixed position, or track moving objects, or move in a
disconjugateA vergence is the simultaneous movement of both eyes in opposite directions to obtain or maintain single binocular vision..When a creature with binocular vision looks at an object, the eyes must rotate around a vertical axis so that the projection of the image is in the centre of the retina in both...
(i.e. completely unsynchronized) manner. They may experience
sleepSleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
-wake cycles, or be in a state of chronic wakefulness. They may exhibit some behaviors that can be construed as arising from partial consciousness, such as grinding their teeth, swallowing, smiling, shedding tears, grunting, moaning, or screaming without any apparent external
stimulusIn physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....
.
Individuals in PVS are seldom on any life-sustaining equipment other than a
feeding tubeA feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by swallowing. The state of being fed by a feeding tube is called gavage, enteral feeding or tube feeding...
because the brainstem, the center of vegetative functions (such as heart rate and rhythm, respiration, and gastrointestinal activity) is relatively intact (Emmett, 1989).
Causes
There are three causes of PVS (persistent vegetative state):
- Acute traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
- Non-traumatic: neurodegenerative disorder or metabolic disorder of the brain
- Severe congenital abnormality of the central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
Medical books (such as Lippincott, Williams, and Wilkins. (2007). In A Page: Pediatric Signs and Symptoms) describe several potential causes of PVS, which are as follows:
- Bacterial, viral, or fungal infection, including meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
- Increased intracranial pressure, such as a tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
or abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
- Vascular pressure which causes intracranial hemorrhaging or stroke
- Hypoxic ischemic injury (hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, cardiac arrestCardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, arrhythmia, near-drowning)
- Toxins such as uremia, ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, atropineAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
, opiates, leadLead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
, colloidal silverThe medical uses of silver include its incorporation into wound dressings to treat external infections, and its use as an antiseptic and disinfectant in medical appliances...
- Trauma: Concussion, contusion
- Seizure, both nonconvulsive status epilepticus and postconvulsive state (postictal state)
- Electrolyte imbalance, which involves hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
, hypernatremiaHypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...
, hypomagnesemiaHypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
, hypoglycemiaHypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, hyperglycemiaHyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, hypercalcemia, and hypocalcemia
- Postinfectious: Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis is an immune mediated disease of the brain. It usually occurs following a viral infection but may appear following vaccination, bacterial or parasitic infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple...
(ADEM)
- Endocrine disorders such as adrenal insufficiency and thyroid disorders
- Degenerative and metabolic diseases including urea cycle disorders, Reye syndrome, and mitochondrial disease
- Systemic infection and sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
- Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
- Psychogenic
In addition, these authors claim that doctors sometimes use the
mnemonicA mnemonic , or mnemonic device, is any learning technique that aids memory. To improve long term memory, mnemonic systems are used to make memorization easier. Commonly encountered mnemonics are often verbal, such as a very short poem or a special word used to help a person remember something,...
device AEIOU-TIPS to recall portions of the differential diagnosis: Alcohol ingestion and acidosis, Epilepsy and encephalopathy, Infection, Opiates, Uremia, Trauma, Insulin overdose or inflammatory disorders, Poisoning and psychogenic causes, and Shock.
Diagnosis
Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases,
residualA residual is generally a quantity left over at the end of a process. It may refer to:* Residual , in business, one of an ongoing stream of payments for the completion of past achievements...
cognitive functions may remain undetected and patients are diagnosed as being in a persistent vegetative state. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible (Owen et al., 2002). In recent years, a number of studies have demonstrated an important role for
functional neuroimagingFunctional neuroimaging is the use of neuroimaging technology to measure an aspect of brain function, often with a view to understanding the relationship between activity in certain brain areas and specific mental functions...
in the identification of residual cognitive function in persistent vegetative state; this technology is providing new insights into cerebral activity in patients with severe brain damage. Such studies, when successful, may be particularly useful where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected.
Diagnostic experiments
Researchers have begun to use functional neuroimaging studies to study implicit cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Activations in response to sensory stimuli with
positron emission tomographyPositron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET),
functional magnetic resonance imagingFunctional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used to measure the hemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of neuroimaging...
(fMRI), and electrophysiological methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically, clinically, and theoretically complex and needs careful quantitative analysis and interpretation.
For example, PET studies have shown the identification of residual cognitive function in persistent vegetative state. That is, an external stimulation, such as a painful stimulus, still activates 'primary' sensory cortices in these patients but these areas are functionally disconnected from 'higher order' associative areas needed for awareness. These results show that parts of the
cortexThe cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
are indeed still functioning in 'vegetative' patients (Matsuda et al., 2003).
In addition, other PET studies have revealed preserved and consistent responses in predicted regions of auditory cortex in response to intelligible speech stimuli. Moreover, a preliminary fMRI examination revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension (Boly, 2004).
Furthermore, several studies have used PET to assess the central processing of noxious somatosensory stimuli in patients in PVS. Noxious somatosensory stimulation activated midbrain, contralateral
thalamusThe thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical
evoked potentialAn evoked potential is an electrical potential recorded from the nervous system of a human or other animal following presentation of a stimulus, as distinct from spontaneous potentials as detected by electroencephalography or electromyography .Evoked potential amplitudes tend to be low, ranging...
s. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices (Laureys et al., 2002).
Also, there is evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in PVS with different behavioral features, researchers employed PET, MRI and magnetoencephalographic (MEG) responses to sensory stimulation. In three of the five patients, co-registered PET/MRI correlate areas of relatively preserved brain metabolism with isolated fragments of behavior. Two patients had suffered
anoxicHypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
injuries and demonstrated marked decreases in overall cerebral metabolism to 30–40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with higher metabolic rates, that ranged up to 50–80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioral patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioral fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental
mesencephalonThe midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....
and paramedian
thalamusThe thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical– pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains (Schiff et al., 2002).
Misdiagnoses
Misdiagnosis of PVS is not uncommon. One study of 40 patients in the
United KingdomThe United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
reported that 43% of those patients classified as in a PVS were misdiagnosed and another 33% able to recover whilst the study was underway. Some cases of PVS may actually be cases of patients being in an undiagnosed
minimally conscious stateMinimally Conscious State is a disorder of consciousness distinct from Persistent vegetative state and Locked-in syndrome. Unlike persistent vegetative state, patients with MCS have partial preservation of conscious awareness. MCS is a relatively new category of disorders of consciousness. The...
. Since the exact diagnostic criteria of the minimally conscious state were formulated only in 2002, there may be chronic patients diagnosed as PVS before the notion of the minimally conscious state became known.
Whether or not there is conscious awareness in vegetative state is a prominent issue. Three completely different aspects of this issue should be distinguished. First, some patients can be conscious simply because they are misdiagnosed (see above). In fact, they are not in vegetative state. Second, sometimes a patient was correctly diagnosed but, then, examined during a beginning recovery. Third, perhaps some day the very notion of the vegetative state will change so as to include elements of conscious awareness. Inability to disentangle these three cases leads to confusion. An example of such confusion is the response to a recent experiment using
magnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
which revealed that a woman diagnosed with PVS was able to activate predictable portions of her brain in response to the tester's requests that she imagine herself playing tennis or moving from room to room in her house. The brain activity in response to these instructions was indistinguishable from those of healthy patients.
In 2010, Martin Monti and fellow researchers, working at the MRC Cognition and Brain Sciences Unit at the
University of CambridgeThe University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
, reported in an article in the
New England Journal of MedicineThe New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
that some patients in persistent vegetative states actually had enough consciousness to respond to verbal instructions by displaying different pattens of brain activity on fMRI scans. Five out of a total of 54 diagnosed patients were apparently able to respond when instructed to think about one of two different physical activities. One of these five was also able to "answer" yes or no questions, again by imagining one of these two activities. It is unclear, however, whether the fact that portions of the patients' brains light up on fMRI will help these patient assume their own medical decision making. Professor Geraint Rees, Director of the Institute of Cognitive Neuroscience at
University College LondonUniversity College London is a public research university located in London, United Kingdom and the oldest and largest constituent college of the federal University of London...
, responded to the study by observing that:
- "As a clinician, it would be important to satisfy oneself that the individual that you are communicating with is competent to make those decisions. At the moment it is premature to conclude that the individual able to answer 5 out of 6 yes/no questions is fully conscious like you or I."
In contrast,
Jacob M. AppelJacob M. Appel is an American author, bioethicist and social critic. He is best known for his short stories, his work as a playwright, and his writing in the fields of reproductive ethics, organ donation, neuroethics and euthanasia....
of the
Mount Sinai HospitalMount Sinai Hospital may refer to:*Mount Sinai Hospital, New York*Mount Sinai Hospital, Toronto*Mount Sinai Medical Center & Miami Heart Institute, Miami, Florida*Mount Sinai Hospital, Cleveland*Mount Sinai Hospital, Milwaukee...
told UK newspaper
The TelegraphThe Daily Telegraph is a daily morning broadsheet newspaper distributed throughout the United Kingdom and internationally. The newspaper was founded by Arthur B...
that this development could be a welcome step toward clarifying the wishes of such patients. Appel stated:
- `"I see no reason why, if we are truly convinced such patients are communicating, society should not honour their wishes. In fact, as a physician, I think a compelling case can be made that doctors have an ethical obligation to assist such patients by removing treatment. I suspect that, if such individuals are indeed trapped in their bodies, they may be living in great torment and will request to have their care terminated or even active euthanasia
Euthanasia refers to the practice of intentionally ending a life in order to relieve pain and suffering....
."
In November 2011, an publication in
The Lancet presented bedside EEG apparatus and indicated that its signal could be used to detect awareness in three of 16 patients diagnosed in the vegetative state.
Recovery
Many patients emerge spontaneously from a vegetative state within a few weeks. The chances of recovery depend on the extent of injury to the brain and the patient's age — younger patients having a better chance of recovery than older patients. Generally, adults have a 50 percent chance and children a 60 percent chance of recovering consciousness from a PVS within the first 6 months. After a year, the chances that a PVS patient will regain consciousness are very low and most patients who do recover consciousness experience significant disability. The longer a patient is in a PVS, the more severe the resulting disabilities are likely to be. Rehabilitation can contribute to recovery, but many patients never progress to the point of being able to take care of themselves. Recovery after long periods of time in a PVS has been reported on several occasions and are often treated as spectacular events.
There are two dimensions of recovery from a persistent vegetative state: recovery of
consciousnessConsciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...
and recovery of function. Recovery of consciousness can be verified by reliable evidence of
awarenessAwareness is the state or ability to perceive, to feel, or to be conscious of events, objects or sensory patterns. In this level of consciousness, sense data can be confirmed by an observer without necessarily implying understanding. More broadly, it is the state or quality of being aware of...
of self and the environment, consistent voluntary behavioral responses to visual and auditory stimuli, and interaction with others. Recovery of function is characterized by communication, the ability to learn and to perform adaptive tasks, mobility, self-care, and participation in recreational or vocational activities. Recovery of consciousness may occur without functional recovery, but functional recovery cannot occur without recovery of consciousness (Ashwal, 1994).
Possible treatment and cures
Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of
evidence-based medicineEvidence-based medicine or evidence-based practice aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments and diagnostic tests...
. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or
methylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
. Mixed results have been reported using dopaminergic drugs such as
amantadineAmantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
and
bromocriptineBromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
and stimulants such as
dextroamphetamineDextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
. Surgical methods such as deep brain stimulation are used less frequently due to the invasiveness of the procedures. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, etc. Below are some details related to treatments that have demonstrated some hope.
Zolpidem
There is currently limited evidence that the
imidazopyridineThe imidazopyridines are a class of drugs defined by their chemical structure. They are generally GABAA receptor agonists, however recently proton pump inhibitors in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to...
hypnotic drug
zolpidemZolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
(Stilnox/Ambien) can have positive behavioral effects in some PVS patients. The first such putative case is Louis Viljoen, who was hit by a vehicle in 1994, leaving him in a persistent vegetative state. Five years later when Viljoen was having involuntary spasms in his left arm, his physician, H Wally Nel, treated him with zolpidem. Twenty-five minutes after the treatment, Viljoen started murmuring and then conversing, albeit not fluently, with his mother. In magnetic resonance images of his brain before and after treatment with zolpidem, the damaged brain regions, which appeared black and dead before treatment, began to light up with neural activity afterwards. Following seven years of further treatment with zolpidem, Viljoen can now speak in complex sentences and move his head and arms. The physician, Nel, who treated Viljoen claims to have treated 150 further PVS patients with zolpidem and seen improvements in approximately 60% of them.
Additionally, stroke victims and patients with head injuries or brain damage following oxygen deprivation, such as near-drowning victims, have reported significant improvements in speech, motor functions, and concentration after treatment with zolpidem.
A clinical trial of zolpidem involving over 360 PVS patients worldwide is currently underway, and 60% of these patients are showing signs of improvement, although no results have yet been published.
There is one other published case series on the long-term effects of zolpidem on patients in PVS, also authored by Nel & Clauss. The first patient, "L", is a 31 year old male who, before treatment with zolpidem, had been in PVS for three years with a
Glasgow Coma ScaleGlasgow Coma Scale or GCS is a neurological scale that aims to give a reliable, objective way of recording the conscious state of a person for initial as well as subsequent assessment...
of 9. They report that after receiving 10 mg of zolpidem, L is able to engage in meaningful conversation. The maximum effect of the zolpidem is seen one hour after application and wears off after about four hours. By the date of publication in 2006, L had been receiving zolpidem therapy for six years, with no decrease in the effectiveness of treatment, and some gradual long-term improvement in short- and long-term memory. The other two patients in the case series were male, of similar age, and had similar though somewhat lessened responses to zolpidem — the zolpidem worked maximally one hour after application, its effects wore off after four hours, and there was no decrease in effectiveness after several years of daily use.
As yet, few scientific studies have been published on the effectiveness of zolpidem as a treatment for PVS and the results have been sometimes contradictory
Levodopa
In addition, there have been several case studies analyzed that emphasize another pharmacological possibility of treatment for patients in a persistent vegetative state. Three patients whose brains had been damaged by severe head injury recovered from a persistent vegetative state after the administration of a drug called
levodopaL-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
, which boosts the body's
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
levels. In all three cases, the patients were deeply
comaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
tose on arrival to the hospital, remained unresponsive to simple verbal commands, and their condition was unchanged for a lengthy period of time even after intensive treatment including surgery. All three patients were diagnosed as being in a persistent vegetative state for three, seven, and twelve months respectively (Matsuda et al., 2003).
Case 1 describes a 14 year old boy who, three months after his trauma, could not follow moving objects with his eyes and experienced tremor-like involuntary movements as well as hypertonicity (increased tension of the muscles, meaning the muscle tone is abnormally rigid, hampering proper movement). Levodopa was recommended to relieve the patient’s parkinsonian features. Surprisingly, after nine days of treatment the patient’s involuntary movements were reduced and he began to respond toward voices. Three months after treatment, he was able to walk and obtained the intelligence of an elementary school child. One year after his trauma, he was able to walk to high school by himself. Case 2 involves a young adult who underwent
deep brain stimulationDeep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
one year after the trauma and showed no improvement. Levodopa was administered and one year later, once his tubes were removed, he said, “I want to eat sushi and drink beer!” Case 3 describes a middle-aged man who experienced
spasticitySpasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
of his extremities, was administered levodopa, and was able to say his name and address correctly after only two months.
After neurological evaluation, all three cases revealed asymmetrical rigidity or tremor and presynaptic damage in the
dopaminergicDopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
(uses dopamine as neurotransmitter) systems. In conclusion, levodopa should be considered for patients in a persistent vegetative state with atypical features in their limbs and who have MRI evidence of lesions in the dopaminergic pathway, particularly presynaptic lesions in areas such as the
substantia nigraThe substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
or
ventral tegmentumThe ventral tegmentum , better known as the ventral tegmental area , is a group of neurons located close to the midline on the floor of the midbrain...
. Data shows that only 6% of adult patients recover after being in a vegetative state for six to twelve months. This poor recovery rate demonstrates the significance in the rapid recovery of patients that begin levodopa treatment, particularly in those who were in a vegetative state for almost a year.
Baclofen
This unexpected and late recovery of consciousness raises an interesting hypothesis of possible effects of partially regained spinal cord outputs on reactivation of cognition. Other case studies have shown that recovery of consciousness with persistent severe disability 19 months after a non-traumatic brain injury was at least in part triggered and maintained by intrathecal baclofen administration (Sarà M et al., 2007).
Removal of cold intubated oxygen
Another documented case reports recovery of a small number of patients following the removal of assisted respiration with cold oxygen. The researchers found that in many nursing homes and hospitals unheated oxygen is given to non-responsive patients via
tracheal intubationTracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...
. This bypasses the warming of the upper respiratory tract and causes a chilling of aortic blood and chilling of the brain. The researchers describe a small number of cases in which removal of the chilled oxygen was followed by recovery from the PVS and recommend either warming of oxygen with a heated
nebulizerIn medicine, a nebulizer is a device used to administer medication in the form of a mist inhaled into the lungs....
or removal of the assisted oxygen if it is no longer needed. The authors further recommend additional research to determine if this chilling effect may either delay recovery or even may contribute to brain damage.
Bifocal extradural cortical stimulation
In December 2008, Dr Sergio Canavero, Director of the Advanced Neuromodulation Group based in
TurinTurin is a city and major business and cultural centre in northern Italy, capital of the Piedmont region, located mainly on the left bank of the Po River and surrounded by the Alpine arch. The population of the city proper is 909,193 while the population of the urban area is estimated by Eurostat...
,
ItalyItaly , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
and one of the leading experts in the field of cortical stimulation, announced that a girl (Greta) in the permanent vegetative state (i.e. vegetative state lasting more than 12 months), recovered consciousness and was regraded as minimally conscious following several months of
bifocal extradural cortical stimulation (Canavero et al. 2009), a minimally invasive neurosurgical technique he and others developed for the treatment of central pain,
Parkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
,
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
rehabilitation, depression, and other neurologic and psychiatric disorders (Canavero 2009). Simultaneous stimulation of the fronto-parietal "consciousness" network achieved a marked improvement of the default network of the brain. A measure of voluntary resposiveness has been obtained and be fed more normally per os. Previous attempts at deep brain stimulation -
Terri SchiavoThe Terri Schiavo case was a legal battle in the United States between the legal guardians and the parents of Teresa Marie "Terri" Schiavo that lasted from 1998 to 2005...
being one of the patients - failed to restore consciousness.This kind of stimulation can also be guided by results of Transcranial Magnetic Stimulation (TMS) as this was able to transitorily improve a patient in PVS (Dr Pape, Chicago 2009) and another in the minimally conscious state (2010).
Epidemiology
In the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
, it is estimated that there may be between 15,000-40,000 patients who are in a persistent vegetative state, but due to poor nursing home records exact figures are hard to determine.
Ethics and policy
An ongoing debate exists as to how much care, if any, patients in a persistent vegetative state should receive in health system plagued by limited resources. In a case pending before the New Jersey Superior Court,
Betancourt v. TrinitasBetancourt v. Trinitas Hospital is a New Jersey legal case concerning whether or not a hospital may unilitarally refuse care to a patient on the grounds that it is futile to prolong the person's life because there is little chance that the condition will improve...
, a community hospital is seeking a ruling that dialysis and CPR for such a patient constitutes futile care. An American bioethicist,
Jacob M. AppelJacob M. Appel is an American author, bioethicist and social critic. He is best known for his short stories, his work as a playwright, and his writing in the fields of reproductive ethics, organ donation, neuroethics and euthanasia....
, has argued that any money spent treating PVS patients would be better spent on other patients with a higher likelihood of recovery.
Notable PVS patients
- Tony Bland
Anthony David Bland was a supporter of Liverpool F.C. injured in the Hillsborough disaster. He suffered severe brain damage that left him in a persistent vegetative state whereby the hospital, with the support of his parents, applied for a court order allowing him to 'die with dignity'...
- Sunny von Bülow
Martha Sharp Crawford von Bülow , known as Sunny von Bülow, was an American heiress and socialite. Her husband, Claus von Bülow, was convicted of attempting her murder by insulin overdose, but the conviction was overturned on appeal...
- Nancy Cruzan
Nancy Beth Cruzan was a figure in the right-to-die movement. After an automobile accident left her in a persistent vegetative state, her family petitioned in courts for three years, as far as the U.S. Supreme Court , to have her feeding tube removed...
- Gary Dockery
Gary French Dockery , was a police officer in Walden, Tennessee who made world headlines after emerging from a 7½ year coma-like state and started talking enthusiastically, recognizing friends and recalling events from past years....
- Eluana Englaro
Eluana Englaro was an Italian woman from Lecco, who entered a persistent vegetative state on January 18, 1992, following a car accident, and subsequently became the focus of a court battle between supporters and opponents of euthanasia...
- Panrawat Kittikorncharoen
Apichet Kittikorncharoen was a Thai singer known under the stage name Big D2B. He studied film at Bangkok University and was part of RS Promotion's trio boy band D2B...
- Vice Vukov
Vice Vukov was a Croatian singer and politician.-Biography:During the 1960s, Vukov was one of the most popular singers in Yugoslavia, appearing at the Eurovision Song Contest 1963 with the song "Brodovi" and at the Eurovision Song Contest 1965 with the song "Čežnja".In the aftermath of the...
- Haleigh Poutre
Haleigh Poutre is an American child and the subject of a multi-pronged legal controversy. On September 11, 2005, Poutre was hospitalized with severe brain injuries after she was allegedly beaten into a coma by Jason Strickland and Holli Strickland, her stepfather and maternal aunt respectively.The...
- Karen Ann Quinlan
Karen Ann Quinlan was an important figure in the history of the right to die controversy in the United States....
- Terri Schiavo
The Terri Schiavo case was a legal battle in the United States between the legal guardians and the parents of Teresa Marie "Terri" Schiavo that lasted from 1998 to 2005...
- Aruna Shanbaug
Aruna Shanbaug is a nurse from Haldipur, Uttar Kannada, Karnataka in India. In 1973, while working at King Edward Memorial Hospital, Parel, Mumbai, she was sexually assaulted and has been in a vegetative state since the assault...
- Ariel Sharon
Ariel Sharon is an Israeli statesman and retired general, who served as Israel’s 11th Prime Minister. He has been in a permanent vegetative state since suffering a stroke on 4 January 2006....
- Gustavo Cerati
Gustavo Adrián Cerati Clark is an Argentine rock musician, singer-songwriter, composer and record producer. He was the frontman, lead vocalist, lead guitarist and lead songwriter of the Argentine rock band Soda Stereo, one of the most influential bands of latin rock music. In the early 90s, with...
See also
- Locked-in syndrome
Locked-in syndrome is a condition in which a patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes. Total locked-in syndrome is a version of locked-in syndrome where the eyes are paralyzed as...
- Process Oriented Coma Work
Process Oriented Coma Work, refers to a body of theory and practice for psychotherapeutic work with patients in comatose, vegetative, and other highly withdrawn states of consciousness...
, for an approach to working with residual consciousness in patients in comatose and persistent vegetative states
- Brain death
Brain death is the irreversible end of all brain activity due to total necrosis of the cerebral neurons following loss of brain oxygenation. It should not be confused with a persistent vegetative state...
- Botulism
Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...
- Catatonia
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....
Further reading