Coma and Brain Death: Facts, Myths, and Mysteries

Abstract

Death is one of universal fact that no one can change, but ongoing advanced medical techniques have created equal challenges to nature. The process of death counts complicated grieving, medical treatment, estate planning, organ donation, and legal and ethical issues. When all vital organs and body systems cease to function, there is end of life. The Uniform Determination of Death Act has stated that “an individual who has sustained either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all functions of the entire brain, including the brainstem, is dead.” The legal and clinical concept of brain stem death has differentiated coma as a state of prolonged, profound unconsciousness where a person is unresponsive to painful stimuli, light, or sound and cannot be woken. The chapter aimed to detect the fact, myth, and mystery behind coma and brain death, using a legal, clinical, and traditional view.

1. Introduction

Death is a romantically fictitious mystery since life begins. Societies have perceived life and death as intertwined; the term death itself has been defined in several terms in different cultures. The definition counts complicated grieving, medical treatment, estate planning, organ donation, and legal and ethical issues. When all vital organs and body systems cease to function, there is end of life. The Uniform Determination of Death Act (UDDA) has stated that “an individual who has sustained either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all functions of the entire brain, including the brainstem, is dead” [1]. Before 1968, the concept of brain death was the state of irreversible coma, while loss of cardiorespiratory function was considered as death [2]. The legal and clinical concept of brain stem death has differentiated coma as a state of prolonged, profound unconsciousness where a person is unresponsive to painful stimuli, light, or sound and cannot be woken and lacks a normal wake-sleep cycle [3, 4]. Coma is a complication of underlying illness or any injury on brain but not a result of brain death. People in coma live in a deep unconsciousness but are still alive. Similarly, vegetative state occurs when the cerebrum is no longer functional, but the hypothalamus and brain stem continue to function [5]. Though neuroscience has clearly mentioned all the four words, that is, vegetative state, coma, brain stem death, and brain death, separately, the traditional view still make them a controversy sisters. Since the past 50 years, determination of a perfect death is still on the top of controversy. Neurosurgeons described cerebral circulatory arrest as brain death in early 1950s, whereas the death of the nervous system was recoined in 1959. A few months later, Mollaret and Goulon described brain death as irreversible coma having a character like deep coma, apnea, lack of reflexes, polyuria, hypotension, and the absence of brain activity in EEG. The less debated concept of death is permanent cessation of critical functions of the organism as a whole; the cessation of respiration and circulation, neuroendocrine and homeostatic regulation, and consciousness. Only one axiom statement is that humans are mortal beings. When a human carries multiple vital organs to function as a whole, then how does a single organ’s demise, that is, death of a brain stem, lead to death of whole body? The query arises that whether neurologists have purposely given the brain death criterion for organ transplantation. A neurologist at Dartmouth, James Bernat, claimed that when patients having devastating brain trauma turn out into cardiac arrest within a very short period of time, that brain death can be considered as biological death, otherwise both brain death and biological death is separate concept. It is the proposal given before early 80s, but the circumstances have changed. The invasive mechanical ventilation and noninvasive positive pressure ventilation, internal and external defibrillators, dialysis machines, extra corporeal membrane oxygenation, organ transplantation treatment method, the new era of medicine has gain strength to bring back the lost life. A patient with modern life-supporting machine but not having functional brain can be stabilized for a week, or in some cases, their bodies may survive for years. Surviving of organ inside a brain body sounds more like harvesting vital organs inside a living corpse. Some examples of cases like Jahi McMath are giving day by day challenges to doctors for declaration of death; the question is still unanswered: what if Jahi was not examined properly before declaring brain dead? The purpose of this chapter is to describe a better version of coma and brain dead, whether they are myth or mysterious using a legal, clinical, and traditional view. The chapter has been broken into four different subtopics, that is, history of brain death, facts of coma and brain death, myth behind coma and brain death and the last one is mystery behind brain death.

2. History of brain death

The history of death illuminates the combination between the earthly and spiritual in funeral rites as well as the process of grieving, burial, cremation, and the concepts of life after death. The ancient Greeks believed that after the death of a person, his vital essence, that is, psyche, remains alive [6]. They strongly believed that at the moment of death, the psyche or spirit of the dead left the body as a little breath or puff of wind [7]. In Hinduism, a person is dead when a soul leaves the physical body, and it decomposes into five different elements (i.e., earth, water, fire, air, and ether). Toward the 19th and 20th century, modern, western culture began to view death as a fearful, forbidden occurrence [8]. Furthermore, the word coma was derived from the Greek word “Koma” meaning deep sleep and was used by Hippocratic Corpus and by Galen in 2nd century AD. Later, Thomas Sydenham (1624–1689) mentioned the term coma for several cases of fever for deeper form of unresponsiveness [9]. At the mid of 18th century, Sydney Smith (1771–1845) stated that “death must be distinguished from dying.” Traditionally, the concept of death was the lack of circulation of vital fluids. In 1959, in France, the word coma depasse came for the first time. Mollaret and Goulon described an apneic, comatose patient without reflexes or electroencephalographic activity of brain stem but with preserved cardiac and metabolic activities [2]. In 1963, Schwab and his team proposed an absence of EEG activity as the most important evidence of death of the nervous system [10]. In 1968, Ad Hoc Committee of Harvard Medical School published a landmark report defining the criteria for brain death as apneic coma and an absence of elicitable brain-stem reflexes for a period of 24 hours as confirmed by electroencephalogram (EEG). The committee proposed the demise of whole brain function [11]. The day-by-day advancement in medicine science and development of cardiac resuscitative and supportive therapies have led to many desperate efforts to save the dying patient. There was genuine reason to propose criteria for brain death to face the ethical problems created by the hopelessly unconscious patient. In 1979, the President’s Commission for the study of ethical problems in medicine and biomedical research was organized. In the United States, in 1980, the Uniform Determination of Death Act was established, a legal basis for a neurologic determination of death. American Academy of Neurology (AAN) guidelines were put forth in 1995 for the determination of brain death/death by neurologic criteria. In 1994, the AAN published 3 cardinal signs in brain death that are coma, absence of brain stem reflexes, and apnea [12].

3. Facts of coma and brain death

Human brain tolerates only limited physical or metabolic injury; comatose is often a sign of impending irreparable damage to the brain. Alternation of consciousness is a result of Ascending Reticular Activating System (ARAS) on the brain stem and cerebral cortex. ARAS theory proposed that neurons in the upper brain stem that forms reticular of neurons project to forebrain that promotes wakefulness. Most of the neurons are located at monoaminergic and cholinergic cell groups. The first branch is an ascending pathway to the thalamus, which activates thalamic relay neurons that transport information to the cerebral cortex. The neurons in the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) fire most rapidly during wakefulness and rapid eye movement (REM) sleep, which is the stage accompanied by cortical activation, loss of muscle tone in the body, and active dreams. The second branch of ascending arousal system bypasses the thalamus, instead activating neurons in the lateral hypothalamic area and basal forebrain and throughout the cerebral cortex. Monoaminergic neurons fire fastest during wakefulness and slow during non-rapid eye movement (NREM) sleep and stop during REM sleep, whereas cholinergic neurons are active during both wakefulness and REM sleep. Multiple factors such as diffuse lesions or circumscribed lesions with repercussion on ARAS metabolic and toxic factors, intracranial hypertension, cerebral edema, epileptic activity, or any other conditions jointly or separately are responsible for coma [13, 14]. Furthermore, the next theory states that the comatose may result from simple metabolic abnormalities to catastrophic life-threatening mass lesion. The human brain depends completely on the continual contribution of oxygen and glucose. The brain receives approximately 20% of the cardiac range and uses almost 15–20% of all the oxygen and glucose consumed by the whole body. The gray matter consumes 80% of glucose and oxygen consumed by the brain. Any clinical process that causes circulatory collapse or profound hypoxemia as short as fifteen seconds of circulatory collapse can result in loss of consciousness. The structural lesions of central nervous system (CNS) and neural metabolism disruption can lead to comatose. Though the exact pathophysiology of coma is not clear, but some theories suggest that the alternation of electrolytes such as sodium, potassium, and calcium or a condition like hyponatremia or hypercalcemia alters the neuronal metabolism or involves false neurotransmitters. Herniation of anatomical part of CNS or vascular compression or increased intracranial pressure (ICP) may results uncal herniation; that is, shifting of medial portion of temporal lobes, brain stem, and cranial nerve III compression leads to coma [15, 16, 17]. More than half cases of comas are related to head injury or disturbances in the cephalous circulatory system [17]. Intracellular energy metabolisms or chemical physiologies such as oxygen and substrate defects, enzymatic and electrolyte disturbances, inorganic or organic chemical intoxications, disease condition like seizure, mass lesions, and infection are the main recorded reasons for comatose situation of person [18].

The fact of brain death is a clinical syndrome defined by the absence of reflexes with pathways through the brain stem and spinal cord connection to the midbrain, cerebellum, and cerebral hemispheres. The AAN states that the irreversible loss of brain and brain stem function, caused by major hemorrhage, hypoxia, or metabolic dysregulation. The brain stem death is diagnosed based on comprehensive neurologic assessment with the absence of brain stem reflexes and apnea under standardized conditions (blood alcohol content 0.08%; core temperature, i.e., 36°C; systolic blood pressure, i.e., 100 mm Hg; and exclusion of CNS depressant drugs) [19]. Brain stem death is a pathological process resulting from hormonal impairment, hemodynamic imbalance, and a systemic inflammatory response [20]. The mechanism of brain death leads to massive cerebral edema, increased intracranial pressure, diffused neuronal apoptosis, brain hypoperfusion, or direct neuronal injury from a neurological cause of arrest. The raised intracranial pressure alters the Cushing reflex, leading to bradycardia and systemic arterial hypertension. The intracerebral hemorrhage causes overwhelming sympathetic stimulation that causes catecholamine storm, and severe vasoconstriction may result in end-organ dysfunction. Furthermore, there is chances of cerebral and brain stem herniation that again stimulate sympathetic stimulation and result in hypothalamus pituitary axis dysfunction. Hypotension is the next result and reduces the level of circulating ADH, thyroid, and cortisol hormones. Ischemia on the region that leads to metabolic acidosis stimulates release of cytokines and activates coagulation factors and promotes leukocytic proliferation, systemic inflammatory process activation, and further tissue damage^.[21, 22].

The patient must have normal core body temperature because hypothermia can make it difficult to perform a brain death assessment. Sedating or paralyzing drugs can interfere with the assessment of coma or brain stem death. Sufficient time for the body to clear the effects of these medications is required before brain death evaluation. Correction of medical condition like hypotension, hypoglycemic condition, or other blood electrolytes is important before brain death assessment. Brain death is typically diagnosed in an intensive care unit by a trained doctor; some countries ask for two doctors. Three conditions are key to confirm the person as brain dead are persistent coma, absence of brain stem reflexes, and lack of the ability to breath independently [23].

4. Myth behind coma and brain death

The biggest myth inside and outside the medical sciences is whether coma and brain death are the same. The misconception not only limits here; it also point out a question that means loss of all brain parts’ functions or only limit to brain stem death. In countries like the United States, the United Kingdom, and Canada, they have given certain criteria to define brain death and are legally valuable for organ donation. But the question still arises: are those criteria defining brain death as legally or clinically or naturally as well? Still, there are some countries like Nepal and India though, where there is legally written description of brain death, but still death confirms with a straight line on ECG, that is, the cardiorespiratory failure.

Dr. David Greer, professor-a chair of neurology at Boston University School of Medicine has concluded a golden rule for death that if a doctor has doubt for confirmation of death then he should never declare death of the patient one dead. The development of advanced medical instruments like positive pressure ventilator, defibrillators, or the advanced life support and awareness on timely cardiopulmonary resuscitation brought new challenges to define death whether as cessation of all organs, respiration, circulation, or neurological system or only the death of the brain. If neurologists have to follow legally authorized definition of death, then every person, whose brain stem reflexes are functioning, is in their comatose state. Toward 1981, Harvard Brain Death Committee clearly differentiated death and coma as comatose individuals have no discernible central nervous system activity [24]. Hypothetically, reversible unconsciousness having some hope of life is coma, whereas irreversible unconsciousness having no sign of life is death. There is no unity for defining brain death as death worldwide. In 1981, UDDA in the United State of America proposed that death must be made in accordance with accepted medical standards including irreversible cessation and pulmonary functions and irreversible cessation of all functions of the entire brain including brain stem. The AAN redefined brain death in 1995 and updated in 2010 as “irreversible loss of entire brain, including the brainstem, has been determined by the demonstration of complete loss of consciousness (coma), brainstem reflexes and the independent capacity for the ventilatory drive (apnea), in the absence of any factors that imply possible reversibility” [25, 26]. In addition, AAN believes that preserved neuroendocrine function may be present despite irreversible injury of the cerebral hemispheres brainstem and is not inconsistent with whole brain standard of death [26]. Under Australian law, there are two situations to certify death: one is when heart stops working, and another is for organ donation criteria, that is, unresponsive coma, the absence of brain stem reflexes, and the absence respiratory function in clinical setting in which the findings are irreversible. For brain death confirmation, there must be definite clinical or neuroimaging evidence of acute brain pathology such as traumatic brain injury, intracranial hemorrhage, and hypoxic encephalopathy including irreversible loss of neurological function [27]. The Canadian Critical Care Society and Canadian Medical Association accepted new definition for all people in all circumstances. The death can be defined as the permanent cessation of brain function, observably by the absence of consciousness and brainstem reflexes including the ability to breathe independently [28]. When we talk about brain death, it means whole human brain—a complex organ that works for thought, memory, emotion, touch, motor skills, vision, breathing, temperature, hunger, and so on. The brain contains cerebrum, brain stem, and cerebellum. Brain stem is middle part of brain that connects the cerebrum with the spinal cord. Brain stem consists of midbrain, pons, and medulla. Midbrain is the mesencephalon of brain that is a very complex structure containing neuron clusters with nuclei and colliculi, neural pathways, and other structures. It has various functions like hearing, motion, movement, and coordination. Pons is responsible for range of activities such as tear production, chewing, blinking, focusing vision balance, hearing, and facial expression. And the medulla is responsible for heart rhythm, breathing, blood flow, oxygen and carbon dioxide levels, reflex, sneezing, vomiting, coughing and swallowing, and many more. Its main function is to regulate vital organs; the cessation of brain stem leads to loss of all functions of cardinal signs that make life possible.

Next myth roaming around the community is whether the brain stem death is just a fiction. As brain stem is just a small part of whole body, with medical support, the person can breath and can live like a coma patient; then, certifying the patient dead is just like mercy killing. The family refuses to accept the situation, and even it is a critical situation for doctors to take a decision. There should be clear line between coma and brain death; this helps to guide both the doctor and the patient’s family regarding withdrawal of care and prevents the unnecessary expenditure of resources. The patient having organ failure condition and waiting for organ transplantation are benefited on time by getting donor organs. But again, the biggest question arises is that what if health personnel or management started hurrying for organ donation and started certifying dead even to comatose or vegetative or brain stem dead patient? This thought is again a big topic of debate and time-to-time comes as controversy. Almost every country has their legal criteria and a strong documentation process for the certification of death and organ transplantation process. Usually, cadaver donation occurs only when death is confirmed and all the legal processes are completed. For the person who are brain dead, the procurement of viable organ is allowed, even if a patient still has some circulatory or pulmonary function present. No evidence has been recorded of when a patient with brain stem death revived (Table 1).

S. no.	Patient’s information	Country	Diagnosis during death	Date of brain death	Survived	Date of cardiopulmonary death	Remark
1	Jahi McMath (13 yrs female)	California	Oropharyngeal surgery	December 12, 2013	No	June 22, 2018	As per parents, she moved extremities, had maturity of puberty, and got her menstruation too.
2	Pregnant mother (27 yrs Female)	—	Arteriovenous malformation of left frontal-aprietal brain during pregnancy	At 16th week of pregnancy	No	2019	Delivered a healthy baby [29]
3	43-year-old woman	Japan	Head Injury	3rd day of hospitalization	No	168th day	Had Spinal reflexes and automatisms [30]
4	Burns, 41-year-old female	New York	Head Injury	October 2009	Survived on 20, 2009	—	She opened her eyes [31]

Table 1.

Brain death and controversy cases.

These are some cases that challenged the neurology community on whether brain death is ideal death or something else.

5. Mystery behind brain death

Even after death, human dead bodies can move on their own without any external assistance. It sounds creepy, but researchers have found some natural facts regarding the movement. Many cases have been reported by patient’s family members that they have seen movements even after the declaration of brain death by physicians. Some reflexes such as planter, muscle stretch reflex, abdominal reflexes, and finger jerks can be seen in some brain-dead patients. A researcher Alyson Wilson from Central Queensland University in Rockhampton, Australia, reported that human bodies can actually be somewhat restless after death for more than a year [32, 33]. The biggest mystery happened in California in 2013, where with the presence of a single reflex, the whole world would have witnessed that the brain death is not actually death. It is a story about Ms. Jahi McMath, a 13-year-old girl who was declared brain dead after hypoxic brain damage following an elective tonsil surgery on December 12, 2013. Her family contested against the death and moved her to New Jersey, and she was cared by her family at home on a mechanical ventilator. After five years in early 2018, she had some intestinal issues needed for surgery. After the surgery it led to excessive hemorrhage; liver failure and cardiac asystole. It took 5 years for cardiac death after declaration of her brain death. The federal civil rights lawsuit is still ongoing for the certification of date of death. Legally, she was dead 5 years back, whereas from a religious and traditional point of view, the family believes her death happened, when the heart was stopped. Her family strongly claimed that she was alive during those 5 years. They have recorded and released Video 1 (https://www.youtube.com/shorts/7qU2U2jjhMo) in which Jahi had moved her limb in response to verbal stimuli and completed her sexual maturity as she gained her menstrual cycle. Was Jahi’s spinal reflexes and hypothalamic and pituitary function still active in her brain death era [34, 35, 36]? We hear lots of stories regarding limb movements; even some reported the dead body breath during funeral. Though there is a lack of proof, there is evidence reported by mourners that they have noticed the dead body moved, changed position, or moved the hands at the time of their funeral. The mourners of Hindu have seen body raising hand, may be asking for help during their burning process. Some scientists explain these phenomena as normal for brain stem-dead person. The patient confirmed dead with unresponsive come, unreactive pupils, absent oculovestibular response, absent corneal reflexes, apnea, and silence of electrical activity for 30 minutes or longer may experience goose bumps, shivering, extensor movements of the arms, rapid flexion of the elbows, elevation of the arm above the bed, crossing of the hands, reaching hands toward the neck, thoracic area movements like breathing are result of spinal cord and upper cervical cord reflexion phenomena [37]. Reflex movements have been reported to occur in up to 75% of brain-dead patient. The most horrifying movement is Lazarus sign, a spinal reflex arc. The signs last for several seconds; arms rise up, from the body, and then draw into the chest; they even cross over the heart; few seconds later, the arms drop back to the body’s sides [38, 39]. As time passes, progressive disintegration of body tissue happens, which is known as molecular or cellular death. The body tissues stop responding to mechanical, electrical, or chemical stimulation. The molecular death exhibits the sign of death by low temperature or cooling of body, changes in skin, rigor mortis, and putrefaction. Rigor mortis is a state of body muscles, characterized by stiffening, shortening, and opacity of the muscles. Rigor mortis symptoms start from involuntary muscles such as heart muscles involved within an hour after death and then in voluntary muscles appears first in eyelids, jaws then face, neck, and so on. Voluntary muscles consist of a large number of fibers containing myosin and actin. Following death, the fusion of actin and myosin filaments into stiff actinomycin produces rigidity of muscles that is termed as rigor mortis. Further putrefaction consists of destructive tissue changes produced by uncontrolled bacterial multiplication and fermentation or by autolysis. Mummification causes drying of exposed body parts and shriveling of tissues. There is always changes in biochemical molecules inside the body. A team of forensic scientists revealed decomposing dead bodies moved in another direction and altered their position on their own during the 17th month of the study period. The assumption made about the changed position was that the decomposition process, body natural mummification, rigor mortis, putrefaction, and other biochemical changes was a major responsible factors [40, 41].

Comatose usually has some electrical brain activity as it is eye-closed deep state of unconsciousness. Brain death states completely stop working condition; yes, completely means total cessation of electrical activities and cerebral perfusion too. Different countries have their own number of doctors and examining times to confirm brain death. One or two doctors perform neurological examination to look for signs, and if there is no sign of brain activity, doctors reperform the procedure after 6 to 24 hours to make sure the person is brain dead and ready for organ donation. Sometimes, the doctor may order for electroencephalography (EEG) to see any microvolts of brain voltage [42, 43]. A 46-year-old man diagnosed clinically brain dead was in deep coma; brain nerves were unresponsive, and spontaneous breathing was absent; there was no reactivity to external stimuli, but EEG showed fine activity of brain waves. The EEG activity disappeared within 40 hours. The neurophysiological findings revealed at that time though brain stem was dead, the cortical portion was active [44]. A case in the United Kingdom was brought before the family division of the high court of justice, in 2015. A child had choked, leading to diagnosis of brain stem death. The judge explained the father based on expert witness that the brain death of whole brain does not equate to brain stem death, but electrical activity in some area of the brain can be present after the declaration of brain death. In a study conducted from 1984 to 1986 at Loyola University Medical Center, 56 patients were involved, out of which 19.6% had EEG activity following the diagnosis of brain death. Three patterns of EEG activity were observed: low voltage theta or beta activity, sleep-like activity, and alpha-like activity following brain death [45].

A romantic thriller mystery behind brain death is: what if a brain-dead person wakes up and say hi. A 21-year-old man named Zack Dunlap was diagnosed brain dead and confirmed by positron emission tomography (PET) scan after a serious brain injury recovered and discharged from hospital after 48 days. There are several reports available that are attracting the attention of neuroscience time to time. Experts like Professor Robert M Sade, Institute of Human Values in health Care, South Carolina in Charleston strongly explained that those recovered patients were never had brain death. During brain-death determination, there must had some error resulted in FALSE Brain Dead diagnosis [46]. However, it is still mysterious that soon after confirmation, the patients are usually quickly removed from life support. How is it possible?

6. Conclusion

The development of cardiopulmonary resuscitation (CPR) method in medical science brought clinically and legally challenges to doctors for declaration of death. It drew a clear line between coma and brain stem and brain death. Alternation in ARAS system is majorly responsible for coma, whereas diffuse lesion, circumscribed lesion, toxic factors, intracranial hypertension, cerebral edema, and epileptic activity play equal roles. The increased intracranial hemorrhage causes overwhelming sympathetic stimulation that leads to catecholamine storm, and severe vasoconstriction leads to brain stem death. From time to time, the topic of coma and brain stem death becomes a controversy; even sometime doctors get confused about whether a patient taking artificial breath is alive or dead. Several incidents have been documented, when the patient parties have seen movement of extremities; some claimed the patient had obeyed their instruction. But nobody knows the actual fac. There are several accepted theories such as biochemical changes after death, stiffness of muscle, and spinal reflexes that may cause the movement of dead body even after the removal of life support system. Clearance of the mystery and so-called myth behind coma and brain death must be solved as it is one of most critically essential component ethically, legally, and clinically.

Funding

The author has not received any financial support.

Declaration of conflicting interests

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.