A PET Scan of a Normal Brain

In what can only be described as a harrowing instance of misdiagnosis, a Belgian man presumed comatose for 23

years after a near-fatal car crash was actually conscious and paralyzed the entire time. Rom Houben, whose real

state was discovered three years ago but only now made public, could be one of many falsely diagnosed coma

cases, raising serious questions about those diagnosed as "vegetative" and, even more frighteningly, the process by

which vegetative people are removed from life support.

Houben, now in a facility in Brussels and communicating via a computer controlled by his minimally functioning right

hand, came around after his 1983 car accident. But while he could hear every word his doctors spoke, he could not

speak to them, nor could he move his body to communicate with them in any way. For years researchers and doctors

tried to coax a response from Houben, who all along was trapped within his own body, living a life of frustration with

his inability to interact.

"I screamed, but there was nothing to hear," he told the Guardian via his computer.

For over two decades Houben remained in what doctors thought was an unconscious state, though he was fully

conscious of the world going by around him. It wasn't until three years ago when doctors wanted to try a new state-

of-the-art PET scanning system on Houben that they made a startling discovery: the "comatose" man's brain

was functioning almost normally.

For Houben, the discovery of his consciousness by the outside world has been like a "second birth," to put it in his own words. But for science, while the news of Houben's "discovery" is heartening, it will likely rehash the debate over when, if ever, a patient who by all indications of modern science is vegetative should be terminated.

Belgian neurologist Steven Laureys has published a paper on Houben's ordeal suggesting that his case is not

isolated. According to his study, as many as 40 percent of cases diagnosed as vegetative may indeed possess

enough consciousness to not only communicate, but to actually make considerable progress with the right treatment.

Of 44 "vegetative" patients Laureys analyzed, 18 ended up responding to communication.

The idea of losing the ability to communicate with the outside world is terrifying enough, but to then be misdiagnosed

and forgotten -- or deemed a lost cause and slotted for termination -- all while possessing fully functioning mental

capacities is downright unthinkable. The question "how many times have we been wrong?" is one the medical

community is likely loath to ask, but if Houben's case is any indication, it's one that needs to be addressed. If Laureys

analysis is to be believed, there should be many more Houben's out there screaming in silence.

Vegetative state.

Classification[edit]

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 coma: 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.[8]

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.[4] 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 Schiavo, such rulings have generated

widespread controversy.

In the UK, the term '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). 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,[9] a medical diagnosis that it is impossible by any informed medical expectations that the

mental condition will ever improve.[10] 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.[9] 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.[4]

Note that in common usage, the "permanent" and "persistent" definitions are sometimes conflated and used

interchangeably. However, the acronym "PVS" is intended to define a "persistent vegetative state", without

necessarily the connotations of permanence, and is used as such throughout this article.

Bryan Jennett, 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".[6]

The Australian National Health and Medical Research Council has suggested "post coma unresponsiveness"

as an alternative term for "vegetative state" in general.[11]

Signs and symptoms[edit]

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 disconjugate (i.e. completely unsynchronized) manner. They may experience sleep-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 stimulus.

Individuals in PVS are seldom on any life-sustaining equipment other than a feeding tube because

the brainstem, the center of vegetative functions (such as heart rate and rhythm, respiration,

and gastrointestinal activity) is relatively intact (Emmett, 1989).

Causes[edit]

There are three causes of PVS (persistent vegetative state):

1. Acute traumatic brain injury

2. Non-traumatic: neurodegenerative disorder or metabolic disorder of the brain

3. Severe congenital abnormality of the central nervous system.

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

Increased intracranial pressure, such as a tumor or abscess

Vascular pressure which causes intracranial hemorrhaging or stroke

Hypoxic ischemic injury (hypotension, cardiac arrest, arrhythmia, near-drowning)

Toxins such as uremia, ethanol, atropine, opiates, lead, colloidal silver[12]

Trauma: Concussion, contusion

Seizure, both nonconvulsive status epilepticus and postconvulsive state (postictal state)

Electrolyte imbalance, which

involves hyponatremia, hypernatremia, hypomagnesemia, hypoglycemia, hyperglycemia,hypercalcemia,

and hypocalcemia

Postinfectious: Acute disseminated encephalomyelitis (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

Hepatic encephalopathy

Psychogenic[clarification needed]

In addition, these authors claim that doctors sometimes use the mnemonic 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[edit]

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,

residual 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 neuroimaging 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[edit]

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 tomography (PET), functional magnetic resonance imaging (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 cortex 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 thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence

of detectable cortical evoked potentials. 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 anoxic 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 metabolicrates, 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 mesencephalon and paramedian thalamus 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[edit]

Misdiagnosis of PVS is not uncommon. One study of 40 patients in the United Kingdom reported that 43% of

those patients classified as in a PVS were misdiagnosed and another 33% able to recover whilst the study was

underway.[13] Some cases of PVS may actually be cases of patients being in an undiagnosed minimally

conscious state.[14] 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

usingmagnetic resonance imaging 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.[15][16][17]

In 2010, Martin Monti and fellow researchers, working at the MRC Cognition and Brain Sciences Unit at

the University of Cambridge, reported in an article in the New England Journal of Medicine [18] that some

patients in persistent vegetative states responded to verbal instructions by displaying different patterns 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.[19] It is unclear, however, whether the fact that

portions of the patients' brains light up on fMRI could help these patients assume their own medical decision

making.[19]

In November 2011, a 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.[20]

Recovery[edit]

Many patients emerge spontaneously from a vegetative state within a few weeks.[6] 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 circa 50 percent chance and children a 60 percent

chance of recovering consciousness from a PVS within the first 6 months in the case of traumatic brain injury.

For non-traumatic injuries such as strokes, the recovery rate falls to 14% at one year.[21] After this period 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 is often treated as a spectacular event.[citation needed]

There are two dimensions of recovery from a persistent vegetative state: recovery of consciousness and

recovery of function. Recovery of consciousness can be verified by reliable evidence of awareness 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[edit]

Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based

medicine. 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 ormethylphenidate. Mixed results

have been reported using dopaminergic drugs such as amantadine and bromocriptine and stimulants such

as dextroamphetamine.[22] 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[edit]

There is currently limited evidence that the imidazopyridine hypnotic drug zolpidem (Stilnox/Ambien) can have

positive behavioral effects in some people with PVS.[23] As yet, few scientific studies have been published on

the effectiveness and the results have been sometimes contradictory. [24][25]

Levodopa[edit]

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 levodopa, which boosts the body's dopamine levels. In all three cases, the patients were

deeply comatose 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 stimulation 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 spasticity 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 dopaminergic (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 nigra or ventral tegmentum. 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[edit]

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[edit]

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 viatracheal intubation. 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 nebulizer 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.[26]

Bifocal extradural cortical stimulation[edit]

In December 2008, Dr Sergio Canavero, Director of the Advanced Neuromodulation Group based

in Turin, Italy 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 disease, stroke 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 responsiveness

has been obtained. Previous attempts at deep brain stimulation -Terri Schiavo 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[27]) and

another in the minimally conscious state (2010).

Epidemiology[edit]

In the United States, 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.[28]

Ethics and policy[edit]

An ongoing debate exists as to how much care, if any, patients in a persistent vegetative state should receive

in health systems plagued by limited resources. In a case before the New Jersey Superior Court, Betancourt v.

Trinitas, a community hospital sought a ruling that dialysis and CPR for such a patient constitutes futile care.

An American bioethicist, Jacob M. Appel, argued that any money spent treating PVS patients would be better

spent on other patients with a higher likelihood of recovery.[29] The patient died naturally prior to a decision in

the case, resulting in the court finding the issue moot.

In 2010, British and Belgian reported in an article in the New England Journal of Medicine that some patients in

persistent vegetative states actually had enough consciousness to "answer" yes or no questions

on fMRI scans.[30] However, it is unclear whether the fact that portions of the patients' brains light up

on fMRI will help these patient assume their own medical decision making.[30] Professor Geraint Rees, Director

of the Institute of Cognitive Neuroscience at University College 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."[30] In contrast, Jacob M. Appel of the Mount

Sinai Hospital told the Telegraph 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 e

…………………………………………….

The Radical Restructuring of Brain Networks in Comatose PatientsDec. 4, 2012 — Researchers from Inserm, CNRS and the Université Joseph Fourier in Grenoble, in collaboration with Cambridge university, Strasbourg university and clinical practitioners from the Strasbourg University Hospital Centre, have analysed data from 17 comatose patients using functional MRI data. Their research reveals that the brain networks of these patients have been restructured. The results, published in PNAS on 26 November 2012, could help clinical practitioners diagnose comatose patients.

The researchers are focusing on analysing brain networks of brain-damaged comatose (non-traumatised) patients, a state where the individual is considered to be unconscious.The authors of the study used an original graph theory-based methodology, where images were constructed using functional MRI data at rest and using robust statistical signal-processing methods. Local and overall effectiveness indices of functional brain networks were obtained for 17 brain-damaged patients and 20 healthy volunteers.Correlations in 417 brain regions were extracted to produce brain connection graphs using the statistically significant correlations.Inserm unit 836 "Grenoble Institut des neurosciences," CNRS researchers from the "GIPSA lab" and from the Behavioural and Clinical Neuroscience Institute in Cambridge, in collaboration with clinical practitioners from the Strasbourg University Hospital Centre, have been able to highlight restructured brain networks in brain-damaged (non-traumatized) comatose patients.Through comparisons with the healthy subjects, the results demonstrate that the overall cerebral connectivity is preserved in comatose patients. By analysing the connectivity at a local level, the authors of the study have observed that some brain regions ("hubs"), which are highly connected in healthy volunteers, are less well connected in comatose patients. Conversely, the less densely connected regions in the network in healthy subjects become "hubs" in comatose patients.Brain imaging obtained from connectivity graphsThe connectivity graph method is used to summarize in a single image data acquired through MRI scanning. It translates the effectiveness of connections in a single region compared to all the others. By grouping the most interconnected regions, modules are revealed (each represented by a different colour). Patients and healthy volunteers both have different models in their spatial location, representing radical alterations to the brain connections.According to current hypotheses, consciousness disorders in persistently comatose patients could be linked to disconnection phenomena between specific cortical regions, particularly the precuneus. The results of this study also point in this direction. "From an overall perspective, the topology of brain connections resists well to traumatism by reorganising the most interconnected regions in the network. It therefore seems that comas may be linked to changes in the location of "hubs" among the brain networks" suggests Chantal Delon Martin, an Inserm researcher.An assessment of brain injury and comasPatients with brain injury may go through various clinically-defined states: vegetative state that ischaracterized by the preserved sleep-wake cycle (eyes opening spontaneously, autonomous breathing, etc.); minimally conscious state where patients have partially preserved environmental consciousness (eye movement capacity, reaction to stimulation); locked in syndrome where the patient is paralysed but conscious (communication using eyes); brain death when the coma is irreversible flat line EEG, no blood flow).Coma (from the Greek κῶμα kôma meaning "deep sleep") is one of the different states where self awareness and consciousness of the outside world is eradicated further to an accident (cerebral, cardiac, etc.). There are two coma phases: the "acute" coma phase (a few days after the accident) and the "chronic" phase (one month or more). Brain restructuring was observed by researchers during the "acute" phase, when it is not known which coma type the patient will develop.Assessments of brain injuries in comatose patients are currently conducted through clinical examination, morphological MRI, evoked potentials and by SPECT (Single-photon emission computed tomography) or TEP (Positron emission tomography (PET). "The results of this study could help clinical practitioners in the difficult diagnosis process for comatose patients, since this method makes it possible to characterize each patient individually", conclude the researchers.

………………………………………

New Test for Consciousness in 'Comatose' Patients

he Coma Science Group (CRCyclotron, University of Liège /Liège University Hospital), led by Dr Steven Laureys, has developed, along with its partners in London, Ontario, (Canada) and Cambridge (England), a portable test which will permit a simpler and less expensive diagnosis of 'vegetative' patients who still have consciousness, despite the fact that they do not have the means to express it.

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The researchers' conclusions are published this week in The Lancet.The desire to develop this simple test of consciousness, at the patient's bedside, follows on from previous research carried out by the Coma Science Group. Professor Steven Laureys and his colleagues had in effect already demonstrated, in 2009, that 40% of so-called 'vegetative' patients had been badly diagnosed and that in reality they retained a certain degree of consciousness. Following on from this

study Laureys' team at the University Hospital of Liège, on the recommendation of the Federal Health Service, was able to prescribe the compulsory use of a specially designed scale of consciousness (the coma recovery scale), now used in every coma specialist centre in Belgium.In 2010 the Coma Science Group researchers and their colleagues at Cambridge (England) made another fundamental breakthrough in showing that it was possible to communicate with 'vegetative' patients through the means of scanners whose technology was based on functional magnetic resonance imaging (fMRI). Classically, the clinical evaluation of coma always proceeded via a muscular response to a stimulus. This study showed that, thanks to fMRI, a doctor could detect traces of consciousness and even communicate with so-called 'vegetative' patients due to the fact that they mentally responded in an appropriate manner to a task suggested by the evaluator. Scientifically revolutionary, using functional magnetic resonance imaging in the evaluation of comas is nevertheless very expensive, and not every hospital is equipped with or has access to it.The new test described this week in The Lancet should change this situation. "As doctors, we as a rule ask the patient to respond to a simple command, such as 'pinch my hand,' to assure us that the patient is conscious. When we obtain a response, everything is fine, but if we cannot detect a response that does not necessarily mean to say that the patient is unconscious. Sometimes he or she cannot move because injuries have affected the nerves, the spinal cord or the brain," explains Dr Laureys. "With our new test, we also ask patients to move their hand or their foot, but we no longer have confidence in the muscular response. We measure the activity of the motor cortex directly using electroencephalography (EEG), a cheaper method which is widespread throughout the hospital centres.""That means that this portable test can be carried out in every health care centre and even at home!" states Camille Chatelle, a neuropsychologist and one of the new study's co-authors.……………………………………

Functional neuroimagingFrom Wikipedia, the free encyclopedia

Functional magnetic resonance imaging data

Functional 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. It is primarily used as a research tool in cognitive neuroscience, cognitive

psychology, neuropsychology, andsocial neuroscience.

Contents

  [hide] 

1   Overview

2   Functional neuroimaging topics

3   Critique and careful interpretation

4   See also

5   References

6   Further reading

7   External links

Overview[edit]

Common methods of functional neuroimaging include

Positron emission tomography  (PET),

Functional magnetic resonance imaging  (fMRI),

multichannel electroencephalography (EEG),

magnetoencephalography  (MEG),

near infrared spectroscopic imaging  (NIRSI), and

Single photon emission computed tomography  (SPECT)

PET, fMRI and NIRSI can measure localized changes in cerebral blood flow related to neural activity. These

changes are referred to asactivations. Regions of the brain which are activated when a subject performs a

particular task may play a role in the neural computations which contribute to the behaviour. For instance,

widespread activation of the occipital lobe is typically seen in tasks which involve visual stimulation (compared

with tasks that do not). This part of the brain receives signals from the retina and is believed to play a role

in visual perception.

Other methods of neuroimaging involve recording of electrical currents or magnetic fields, for example EEG

and MEG. Different methods have different advantages for research; for instance, MEG measures brain activity

with high temporal resolution (down to the millsecond level), but is limited in its ability to localize that activity.

fMRI does a much better job of localizing brain activity for spatial resolution, but at the cost of speed.[1]

Functional neuroimaging topics[edit]

The measure used in a particular study is generally related to the particular question being addressed.

Measurement limitations vary amongst the techniques. For instance, MEG and EEG record the magnetic or

electrical fluctuations that occur when a population of neurons is active. These methods are excellent for

measuring the time-course of neural events (on the order of milliseconds,) but generally bad at measuring

where those events happen. PET and fMRI measure changes in the composition of blood near a neural event.

Because measurable blood changes are slow (on the order of seconds), these methods are much worse at

measuring the time-course of neural events, but are generally better at measuring the location.

Traditional "activation studies" focus on determining distributed patterns of brain activity associated with

specific tasks. However, scientists are able to more thoroughly understand brain function by studying the

interaction of distinct brain regions, as a great deal of neural processing is performed by an integrated network

of several regions of the brain. An active area of neuroimaging research involves examining the functional

connectivity of spatially remote brain regions. Functional connectivity analyses allow the characterization of

interregional neural interactions during particular cognitive or motor tasks or merely from spontaneous activity

during rest. FMRI and PET enable creation of functional connectivity maps of distinct spatial distributions of

temporally correlated brain regions called functional networks. Several studies using neuroimaging techniques

have also established that posterior visual areas in blind individuals may be active during the performance of

nonvisual tasks such as Braille reading, memory retrieval, and auditory localization as well as other auditory

functions.[2]

A direct method to measure functional connectivity is to observe how stimulation of one part of the brain will

affect other areas. This can be done noninvasively in humans by combining transcranial magnetic

stimulation with one of the neuroimaging tools such as PET, fMRI, or EEG. Massimini et al. (Science,

September 30, 2005) used EEG to record how activity spreads from the stimulated site. They reported that

in non-REM sleep, although the brain responds vigorously to stimulation, functional connectivity is much

attenuated from its level during wakefulness. Thus, during deep sleep, "brain areas do not talk to each other".

Functional neuroimaging draws on data from many areas other than cognitive neuroscience and social

neuroscience, including biological sciences (such as neuroanatomy and neurophysiology), physics and maths,

to further develop and refine the technology.

Critique and careful interpretation[edit]

Functional neuroimaging studies have to be carefully designed and interpreted with care. Statistical analysis

(often using a technique called statistical parametric mapping) is often needed so that the different sources of

activation within the brain can be distinguished from one another. This can be particularly challenging when

considering processes which are difficult to conceptualise or have no easily definable task associated with

them (for example belief and consciousness).

Functional neuroimaging of interesting phenomena often gets cited in the press. In one case a group of

prominent functional neuroimaging researchers felt compelled to write a letter to New York Times in response

to an op-ed article about a study of so-calledneuropolitics.[3]

They argued that some of the interpretations of the study were "scientifically unfounded".[4]

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Patients in a Minimally Conscious State Remain Capable of Dreaming During Their SleepAug. 30, 2011 — The question of sleep in patients with seriously altered states of consciousness has rarely been studied. Do 'vegetative' patients (now also called patients in a state of unresponsive wakefulness) or minimally conscious state patients experience normal sleep? Up until now the distinction between the two patient populations had not been taken into account by electrophysiological studies. Yet if the vegetative state opens no conscious door onto the external world, the state of minimal consciousness for its part assumes a residual consciousness of the environment, certainly fluctuating but real.

It is this difference which has led a group of researchers at the Coma Science Group (University of Liège and CHU Liège) and the universities of Wisconsin and Milan to compare the sleep of these two types of brain damaged patients. The results of their study are published this week in the journal Brain. They demonstrate once again the necessity of an adapted and specific medical care for each of these states.The researchers' work rested on a sample of 11 subjects (6 in a state of minimal consciousness and 5 in a vegetative state) and made use of high density (256 electrodes) electroencephalography (EEG). The goal was to determine the structure of sleep within the two types of patient. 'We used as a marker of arousal the fact that the subject had his/her eyes open and muscle tone, and as a marker of sleep the fact that the patient had closed eyes and muscle inactivity,' points out Dr Steven Laureys, the Director of the Coma Science Group.The high density EEG revealed that the brain's electrical activity differed very little between sleep and wake states in patients in a vegetative state. On the other hand the sleep of patients in a minimally conscious state had characteristics very close to that of normal sleep in a healthy subject. They showed changes in "slow wave" activity in the front of the brain considered important for learning and neural plasticity. It also appeared that these patients produced NREM (non rapid eye movement) slow wave sleep and REM (rapid eye movement) sleep, which is the support for dream activity.'Everything thus indicates that they have access to dreaming,' emphasises Steven Laureys. 'As a result, we can legitimately suppose that they still have a form of consciousness of self in addition to a certain consciousness of the external world.'The study published in Brain brings to light a relationship between the electrophysiology of sleep and the degree of consciousness in severely brain damaged patients. Thus, once validated, the method used could constitute an additional tool to evaluate, in a routine clinical setting, the potential maintenance of a residual consciousness in these patients.……………………………….

Misdiagnosis Of Disorders Of Consciousness Still CommonplaceJuly 21, 2009 — A sixteen-month study of consensus-based diagnosis of patients with disorders of consciousness has shown that 41% of cases of minimally conscious state (MCS) were misdiagnosed as vegetative state (VS), a condition associated with a much lower chance of recovery. Researchers have demonstrated that standardized neurobehavioral assessment is more sensitive than diagnoses determined by clinical consensus.

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Steven Laureys, from the University of Liege, Belgium, worked with a team of researchers, including Caroline Schnakers and Joseph Giacino, to compare consensus-based diagnoses of VS and MCS to those based on the JFK Coma Recovery Scale-Revised (CRS-R), a well-established standardized neurobehavioral rating scale. Laureys said, "Differentiating the vegetative from the minimally conscious state is often one of the most challenging tasks facing clinicians involved in the care of patients with disorders of consciousness. Misdiagnosis can lead to grave consequences, especially in end-of-life decision-making".The researchers prospectively followed 103 patients with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from the CRS-R. They found that of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. According to Laureys, "It is likely that the examiners' reliance on unstructured bedside observations contributed to the high rate of misdiagnosis of VS patients. Unlike traditional bedside assessment, the CRS-R guards against misdiagnosis by incorporating items that directly reflect the existing diagnostic criteria for MCS, and by operationalizing scoring criteria for the identification of behaviors associated with consciousness".The researchers conclude, "The results of this study suggest that the systematic use of a sensitive standardized neurobehavioral assessment scale may help decrease diagnostic error and limit diagnostic uncertainty".……………………………………

In a recent study of patients in vegetative and minimally conscious states, researchers played a tone immediately prior to blowing air into a patient's eye. After some time training, the patients would start to blink when the tone played but before the air puff to the eye. (Credit: iStockphoto/Eric Hood)

Individuals In Vegetative States Can Learn, Scientists FindSep. 21, 2009 — Scientists have found that some individuals in the vegetative and minimally conscious states, despite lacking the means of reporting awareness themselves, can learn and thereby demonstrate at least a partial consciousness. Their findings are reported in the online edition of Nature Neuroscience.

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It is the first time that scientists have tested whether patients in vegetative and minimally conscious states can learn. By establishing that they can, it is believed that this simple test will enable practitioners to assess the patient's consciousness without the need of imaging.This study was done as a collaborative effort between the University of Buenos Aires (Argentina), the University of Cambridge (UK) and the Institute of Cognitive Neurology (Argentina). By using classical Pavlonian conditioning, the researchers played a tone immediately prior to blowing air into a patient's eye. After some time training, the patients would start to blink when the tone played but before the air puff to the eye.This learning requires conscious awareness of the relation between stimuli -- the tone precedes and predicts the puff of air to the eye. This type of learning was not seen in the control subjects, volunteers who had been under anaesthesia.

The researchers believe that the fact that these patients can learn associations shows that they can form memories and that they may benefit from rehabilitation.Lead author Dr Tristan Bekinschtein, from the University of Cambridge's Wolfson Brain Imaging Unit, said: "This test will hopefully become a useful, simple tool to test for consciousness without the need for imaging or instructions. Additionally, this research suggests that if the patient shows learning, then they are likely to recover to some degree."In 2006, the Cambridge Impaired Consciousness Group at the Wolfson Brain Imaging Unit showed, using functional imaging, showed that patients in vegetative states (as defined by behavioural assessment in the clinic) can in fact be conscious despite being unable to show consistent voluntary movements.The paper 'Classical conditioning in the vegetative and minimally conscious state' will be published in the Advanced Online Publication of Nature Neuroscience on 20 September 2009.This study was funded by an Antorchas Foundation grant (T.A.B.), a Marie Curie IIF grant (T.A.B.), a StartUp grant (F.F.M.), the Human Frontiers Science Program (M.S.) and a Medical Research Council Acute Brain Injury Collaborative grant.……………………………

Traumatic Brain Injury Patients Treated With Anti-Spasm Agent Partially Recover from Disorders of ConsciousnessJune 12, 2013 — At the International Neuromodulation Society's 11th World Congress, Dr. Stefanos Korfias of the Department of Neurosurgery at the University of Athens will present the results of a clinical study led by Professor Damianos Sakas, which showed that two of six in-patients studied at Evangelismos Hospital in Athens steadily emerged from minimally conscious state after receiving intrathecal baclofen (ITB) after traumatic brain injury.

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The drug relaxes spasticity that can result from brain injury and may be used to facilitate care, but is not normally used to restore function. The patients, a 24-year-old man and a 29-year-old man, had been in minimally conscious states for three years and 18 months, respectively. Their scores on a revised coma recovery scale (with a maximum of 23) increased from 10 -- 19 and 11 -- 22, respectively.Minimally conscious state is defined as a consciousness disorder in which a patient shows fluctuating, but not reproducible, signs of self-awareness and the surroundings. Most patients in a minimally conscious state also have moderate to severe spasticity as a result of their injuries.Dr. Konstantinos Margetis, who contributed significantly to this study, notes that some sporadic case reports have suggested a potential beneficial effect of ITB in recovery from disorders of consciousness. He and colleagues decided to search for the effect in a systematic way. ITB was indicated in this study, he said, and in the previous case series, to reduce spasticity since it facilitates care and probably minimizes some spasticity complications."The improvement in the level of consciousness was a very pleasant observation for us," he said. "It might have been due to an additional beneficial effect of receiving intrathecal baclofen in this group of patients." All six patients improved spasticity scores with treatment, and the two who also made gains in recovering consciousness apparently retained some ability, despite their brain injury, to sustain an awake, alert, and oriented state that might have been enhanced by the treatment. He hypothesizes the mechanism of this observed effect could be associated with the action of baclofen on receptors in the orexin system, which plays a role in maintaining wakefulness, and in the thalamic reticular nucleus, a brain structure associated with consciousness.Next he would like to see a larger, multi-center study evaluate such factors as brain and nervous system activity observed in functional and neural pathway imaging (fMRI and DTI MRI respectively); analysis of

changes in neurotransmitters in the cerebrospinal fluid; and tracking electrical activity in neural networks or response to a stimulus (EEG and evoked potential recordings)."A complete research protocol designed with input from other disciplines will attempt to investigate every facet of this complex subject," he remarked. "A study like that will allow for definite conclusions about the role of intrathecal baclofen in the recovery of the disorders of consciousness. While we feel that the current results might lower the threshold for intrathecal baclofen treatment in spasticity patients with disorders of consciousness, should a multi-center a study establish a definite role for intrathecal baclofen in disorders of consciousness, then the potential will be very promising indeed."

Glasgow Coma Scale

This gives a reliable, objective way of recording the conscious state of a person.[1] It can be used by medical and nursing staff for initial and continuing assessment. It has value in predicting ultimate outcome. Three types of response are independently assessed and are recorded on an appropriate chart (and the overall score is made by summing the scores).The calculator has been adapted to estimate the Glasgow verbal score from the Glasgow eye and motor scores in intubated patients.[2] 

There is a Paediatric Glasgow Coma Scale applicable to infants too young

to speak - and the equivalent infant responses are given in the various sections below.[3]

1. Best Motor Response (M) - 6 gradesApply varied painful stimulus: trapezius squeeze, earlobe pinch, supraorbital pressure, sternal rub, nail-bed pressure etc:

1. No response to pain.2. Extensor posturing to

pain: The stimulus causes limb extension (abduction, internal rotation of shoulder, pronation of forearm, wrist extension) - decerebrate posture.

3. Abnormal flexor response to pain: Stimulus causes abnormal flexion of limbs (adduction of arm, internal rotation of shoulder, pronation of forearm, wrist flexion - decorticate posture.

4. Withdraws to pain: Pulls limb away from painful stimulus.Infant: withdraws from pain.

5. Localizing response to pain: Purposeful movements towards changing painful stimuli is a 'localizing' response.Infant: withdraws from touch

6. Obeying command: The patient does simple things you ask (beware of

1 pt - No response to pain2 pts - Extensor posturing to pain3 pts - Abnormal Flexor response to pain4 pts - Withdraws to pain5 pts - Localizing response to pain6 pts - Obeying commands

accepting a grasp reflex in this category).Infant: moves spontaneously or purposefully

2. Best Verbal Response (V) - 5 gradesRecord best level of speech. If patient is intubated, a "derived verbal score" is calculated via a linear regression prediction.

1. No verbal response.2. Incomprehensible

speech: Moaning but no words.Infant: Inconsolable, agitated.

3. Inappropriate speech: Random or exclamatory articulated speech, but no conversational exchange.Infant: Inconsistantly inconsolable, moaning.

4. Confused conversation: Patient responds to questions in a conversational manner but some disorientation and confusion.Infant: Cries but consolable, inappropriate interactions.

5. Orientated: Patient 'knows who he is, where he is and why, the year, season, and month.Infant: Smiles, orientated to sounds, follows objects, interacts.

UNABLE TO ASSESS (eg Intubated)1 pt - None2 pts - Incomprehensible speech3 pts - Inappropriate speech4 pts - Confused conversation5 pts - Orientated

3. Best eye response (E) - 4 grades1. No eye opening;2. Opening to response to

pain to limbs as above3. Eye opening in response

any speech (or shout, not necessarily request to open eyes);

4. Spontaneous eye opening.

Glasgow Coma Scale Score (max 15): (Derived Verbal score:   )

Interpretation of Symptoms: (Severe: 8 or less; Moderate: 9-12; Mild: 13 or more)

The calculator above has been adapted from The Lancet, Vol 2 (7872) Teasdale G, Jennett B; Assessment of coma and impaired

consciousness. A practical scale. pp81-4. ©1974 with permission from Elsevier. The calculator also provides calculated scores for intubated patients using linear regression as described in Meredith W, Rutledge

R, Fakhry SM, et al; The conundrum of the Glasgow Coma Scale in intubated patients: a linear regression prediction of the Glasgow verbal

score from the Glasgow eye and motor scores. J Trauma. 1998 May; 44(5):839-44.

Some centres score GCS out of 14, not 15, omitting "withdrawal to pain". As well as the total figure the GCS can be expressed as subscores: GCS=15; M6,V5,E4 (motor, verbal and eye-opening responses)

Abbreviated coma scale (AVPU)

This sometimes used in the initial assessment ('primary survey') of the critically ill.

1 pt - No eye opening2 pts - Eye opening in response to pain3 pts - Eye opening in response to speech4 pts - Spontaneous eye opening

Reset

A = alert V = responds to vocal stimuli P = responds to pain U = unresponsive

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