Persistent vegetative state after traumatic brain injury-a case report and review of the literature

Traumatic brain injury (TBI) is the most common cause of death or life-long severe disability worldwide. Progress in medicine, diagnostic neuroimaging, and critical care management has considerably increased the number of patients who survive severe acute TBI that in the past would have died1. Typically some of these patients recover from coma within the first few days after the insult, while others take more time and go through different stages before fully or partially recovering awareness e.g., minimally conscious state (MCS), vegetative state (VS) or brain death. During the early stages of recovery, external manifestations may not be immediately apparent and repeated bedside examinations over time are necessary to ensure proper diagnosis. This difficulty is reflected by frequent misdiagnoses of coma, MCS, VS and locked-in syndrome (LIS)2,3. Although all of these disorders involve severe alteration of consciousness, there are important clinical differences between them that impact on their management. Their correct diagnosis and management has been the subject of increasing scrutiny over the past few decades4-6. Further new technologies, most notably functional magnetic resonance imaging (fMRI) and electrophysiological procedures that have emerged during the last 5 years have raised new questions about the relationship between brain


Introduction
Traumatic brain injury (TBI) is the most common cause of death or life-long severe disability worldwide.Progress in medicine, diagnostic neuroimaging, and critical care management has considerably increased the number of patients who survive severe acute TBI that in the past would have died 1 .Typically some of these patients recover from coma within the first few days after the insult, while others take more time and go through different stages before fully or partially recovering awareness e.g., minimally conscious state (MCS), vegetative state (VS) or brain death.During the early stages of recovery, external manifestations may not be imme-diately apparent and repeated bedside examinations over time are necessary to ensure proper diagnosis.This difficulty is reflected by frequent misdiagnoses of coma, MCS, VS and locked-in syndrome (LIS) 2,3 .Although all of these disorders involve severe alteration of consciousness, there are important clinical differences between them that impact on their management.Their correct diagnosis and management has been the subject of increasing scrutiny over the past few decades 4-6 .Further new technologies, most notably functional magnetic resonance imaging (fMRI) and electrophysiological procedures that have emerged during the last 5 years have raised new questions about the relationship between brain function and consciousness.The results of these studies, along with well-documented reports of significant late recovery of some persistent vegetative state (PVS) patients, has challenged the long-held view that restoration of function in the severely TBI patients is not possible and that all forms of treatment are futile in these patients.Further naming these patients as "vegetative" has been misinterpreted by many groups that the patient is no more a human but "vegetable" like.We appreciate the recent move to avoid the pejorative medical term "PVS" and replace it by new, more humane and appropriate name "Unresponsive Wakefulness Syndrome"(UWS) 7 .Medical professionals face difficult medical, ethical and social dilemmas in management of these cases.8 The ethical issues arise from their chronic non-cognitive existence as they depend on others to provide for all their needs, which brings in financial concerns.Conflicts arise when physicians recommend withdrawal of life sustaining treatment (LST) over the objections of surrogates.We present a case of young boy who is in a PVS following TBI and attempt to review the specific ethical aspects of managing these patients.In this paper we will continue to refer 'PVS' because the term is so ingrained in medical and legal terminology, till the consensus on new terminology is reached.
Case Report: A 14 year old Malay male boy, the only child of a single mother who had sent him to JAKIM centre for study was admitted to the surgical intensive care unit at our hospital Tangku Ampuan Afzan (HTAA) on 13-3-2012 after a road traffic accident.He had unremarkable past medical history.On arrival to the emergency department he was comatose, with Glasgow Coma Scale (GCS) of 3/15.Pupils were fixed and dilated.He had hematoma on the left side and back of the skull (pariato-occipital hematoma).He was intubated and resuscitated following which his cardiovascular system resumed activity.A computerized scan of the head was performed which revealed left tempo-parietal subdural haemorrhage and brain swelling.The haematoma was removed and decompression craniotomy and fascio-duraplasty was performed.On day 3 after the accident; the patient started showing spontaneous eye opening.He sometimes seemed to be awake, although his eyes could not follow moving objects and he could not obey simple verbal commands of physicians and nurses.He was able to breathe without mechanical support and his cardiovascular, respiratory, renal, and gastrointestinal functions were sound, but he was doubly incontinent.He could open his eyes to auditory stimuli and his mother claimed that he was communicating with her by eye movements.Further examination by our neurologist revealed that he was in VS.Subsequently he developed increased tone and spasticity in upper limbs and increased tone but no spasticity in lower limbs.He had brisk reflexes and up-going planter reflexes.He was managed with passive physiotherapy and nasogastric (NG) tube feeding.He was discharged home with a diagnosis of PVS on 18-7-2012 with spontaneous breathing and GCS of 10/15 on NG tube feeding tab baclofen 5mg TDS and passive physiotherapy.He was readmitted one week later with respiratory tract infection.As per his mother he developed cough and choking after feeding.While in the hospital he developed sudden desaturation with tachypnea of 34 breaths per minute, temp 38 o C and Spo 2 78-82%.He was intubated and sedated.
Vital signs: BP 138/86, pulse 120, ABG (arterial blood gas) analysis showed type 1 respiratory failure.He was diagnosed of type 1 respiratory failure secondary to aspiration pneumonia with underlying pharyngeal dysphagia.In the ward he developed hypokalemia 2.6 mEq/L and occult gastro-intestinal bleed.Sputum culture and sensitivity grew pseudomonas aerogenosa.His condition progressively deteriorated into a state of septic shock.He was put on IV sulperazone 2gm BD, IV esomeprazol 40mg OD and nebulised salbutamol.Mother was told about the poor status of her son and given clear message that her son's end was imminent.She was consoled that children are pure and innocent, and Paradise was assured to them in the life to come.She consented to do not resuscitate (DNR) her son in case of cardio-respiratory arrest.Due to prolonged ventilation, tracheotomy was suggested and mother consented for it.He responded to treatment and on 19-8-12 his GCS was E4V1M1; eyes were open with blank stare.He was comfortable, a-febrile, BP 110/60, pulse 100/mint.He was able to breathe without mechanical support through tracheotomy.His cardiovascular, respiratory, renal, and gastrointestinal functions were normal, but remained doubly incontinent.He tolerated NG tube feeding.He was discharged home on a Ripple mattress, advised regular chest physiotherapy, and further follow-up at our rehabilitation clinic.As of writing, 8 months after the injury, he had spastic quadriplegia, aphonia, dysphagia, and was fully dependent for activities of daily living (ADL).There was not a smile from the child though he was seemingly beautiful and cheerful.His mother looked very composed, seemingly oblivious to the fact that her child was in that situation.

Disorders of Consciousness after TBI
There are two stages in TBI, the primary and the secondary.Primary brain injury is caused initially by trauma which occurs in seconds after the accident and gets worse by a second injury which happens in minutes and hours after this, depending on when skilled medical intervention occurs.TBI can cause a wide range of disorders of consciousness which are sometimes difficult to distinguish 2,3 .To help determine the extent of TBI and the chance for regaining consciousness, physicians classify them into one of six abnormal conscious states: stupor, coma, PVS, MCS, LIS and brain dead.
Stupor: is an excessively long sleep like state from which a person can be awakened only by vigorous external stimuli like loud noise or painful stimuli.TBI can damage areas of the brain stem that control consciousness.
Coma: is a profound state of unconsciousness.The individual is alive but patients show no awareness of themselves or their surroundings and they don't open their eyes either spontaneously or by vigorous stimulation 9 .It is usually caused by either temporary or permanent damage to the reticular system.A patient in coma due to (traumatic or anoxic) brain injury, progresses within 2-4 weeks to one of several conditions including death, VS or the MCS 9,10 .
Prognosis among traumatic survivors is better than in anoxic cases 11 .
Brain death: is diagnosed on the basis of irreversible loss of all brainstem reflexes.These patients need artificial ventilation to survive since they are unable to breathe spontaneously 12 .
Vegetative state: is a neurological condition in which patients appear to be awake; with cycles of eye closure and opening resembling those of sleep and waking but there is no behavioural evidence of awareness.Recent studies have reported that as many as 41% of MCS patients were misdiagnosed as being in a VS 27 .These patients, retain large-scale cortical networks responsible for language processing, despite their inability to communicate reliably 29 .One notable example is Terry Wallis, who in 2003,unexpectedly recovered language and motor abilities 20 years after sustaining a severe TBI and was subsequently found to have evidence of regrowth of brain fibers as revealed by MRI diffusion tensor imaging study 30 .
Locked-in syndrome: is a condition that superficially resembles patients in VS and may be confused with it.In rare cases, it may be difficult to distinguish a PVS from a severe LIS.These patients are awake and conscious but have no means of producing speech, limb or facial movements due to aphonia and quadriplegia.They communicate through eye movements or blinking 26,27 .The classic syndrome involves damage to corticospinal and corticobulbar pathways in the basis pontis 31 .These patients often have full mental function.Once LIS patients become medically stable, they can live several decades if given appropriate medical/nursing care.It is important to recognise this group of patients since eyecontrolled, computer-based communication technology currently allows them to control their environment, use a word processor coupled to a speech synthesizer, and access the worldwide net.Recent surveys show that chronic LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent 32, 33 .One survey of LIS patients found that self-scored perceptions of wellbeing and distress were not significantly worse than those of age matched controls 34 .So these surveys contradict the notion of people who assume that the quality of life of these patients is not worth living.
Management: TBI patients are treated in an acute care hospital where the focus is primarily on saving and stabilizing them medically.Once that is achieved, the next focus is on recovery of function to whatever level possible.They are monitored by important predictors of recovery, including recovery of spontaneous motility, eye tracking, oculo-cephalic reflex, and disappearance of oral automatisms.Recent studies indicate that multidisciplinary approach and early rehabilitation can improve their functional motor outcome and help in faster recov-ery.In principle, it is obligatory to provide them with artificial nutrition and hydration (ANH), usually via a feeding tube and antibiotics as they often get infectious complications like pneumonia, pressure sores and urinary tract infections.Recently, electric stimulation of dorsal column and median nerve has been used, to help in fast recovery 35-37 .Deep brain stimulation is under trial and has provided some promising results 37 .Some pharmacological agents which help in synaptic transmission of dopamine receptors have also been found useful.38 Some authors have reported value of musical stimulation in their recovery 39, 40 .Stem cell therapy is an emerging therapeutic modality with evidence of significant benefits in preclinical stroke models.According to a study, bone marrow stem cell therapy is safe and effective in PVS patients, through lumbar puncture in the sub acute stage 41 .
Once the diagnosis of PVS has been established and there is no demonstrable recovery despite best possible care and early rehabilitation measures over more than twelve months in TBI patients, questions are raised regarding their further active management which calls for extensive resources.With the economic reality that exists in most third world countries, physicians are caught by the divide between what they ought to do and what they can do.Further religious beliefs affect the views of patients and health care professionals, which make the formulation of universal legal and ethical guidelines a challenging task in long term management of these cases.They are discharged to an appropriate medical facility, nursing home, or home care as the case warrants.
We believe that the family's wish to keep a PVS patient alive should be respected in general, but, at the same time, to facilitate appropriate care and avoid inappropriate interventions, health care professionals must share all aspects of the illness with the family in a supportive environment and give them time to come to terms with the emotionally charged decisions they are asked to make for their loved one in PVS.Decisions should focus on better physical, emotional and spiritual care, and by no means any sort of patient abandonment.The intrinsic value and personal dignity of human beings does not change depending on their circumstances.It is permissible for patients either through a prior living will or decisions made by immediate family or surrogate, to refuse any treatment or discontinue it, if treating physicians are of the view that there is little or no hope of recovery.Since TBI patients have no advance directive, the treatment decisions are made by health care professionals or immediate family members/authorized surrogate.The decisions of treatment limitation usually begin with a Do-Not-Resuscitate order (DNR) as it would reduce unnecessary patient suffering and medical care costs.Other decisions range from not to perform surgical procedures, not to start vasoactive drugs, hemo-dialysis or other treatments.This practice arguably allows for physician discretion, and promotes better use of health-care resources.Withdrawal of LST is an area of great difficulty for surrogates and physicians alike.42 Many clinicians do not like to withdraw ANH in a stable PVS patient, rather than when their condition is complicated by critical illness.The patient's family seldom request to withdraw ANH, but favour limiting unnecessary medical interventions that are disproportionate to the expected outcome and would prolong patients suffering.43 There is no justification in Islam to end a human life merely because of the family's and patient's suffering, as patience and endurance are highly regarded and rewarded values in Islam.The concept of "quality of life" not worthy of living often imposed by economic, social and psychological pressures does not exist in Islam.Those who argue that the maintenance of these patients is an unacceptable burden on the society, and they should be disposed of abruptly than allowing them to deteriorate gradually, is completely alien to Islam.The physicians should write explicit orders indicating which treatments can be administered and which should be withheld.Barring a mutually acceptable solution, physicians may decide to cede to the wishes of the family/surrogates, or as a last recourse, involve the judicial system to achieve resolution.On the other hand, despite a number of recent legal cases, the physicians are still not obliged to submit to pressure by the patient's relatives, to give treatment which they believe to be futile or against the patients' best interests.
Once these patients are at the brink of death and death is imminent, then it is obligatory to stop the treatment and allow the nature to take its course when three consultant physicians advise to do so.Death is not to be resisted, but rather accepted as part of the overall divine plan.44

Conclusion:
The management of PVS patients is an extremely difficult and challenging task for rela-tives, medical professionals and society in general.As medical technology advances at a rapid pace, the ability to sustain such patients will improve.Clinical research is needed to continue efforts at researching better ways to manage such patients, and explore novel treatment to facilitate emergence from VS.The stem-cell therapy remains within the experimental arena for the foreseeable future.We need much more data before we make any assertive conclusions about the effect of pharmacological and non-pharmacological treatment in PVS patients.
Under current prevailing conditions, when we are facing escalating health care costs particularly in scarce resource communities, we must establish just mechanisms to deal with these patients and limit the use of expensive treatments of marginal benefit, so that that family can achieve an outcome which, however painful, is compassionate.
Ethical approval: Ethics Committee of International Islamic University Malaysia approved publication of this case report.
Persistent vegetative state after traumatic brain injury