History of Disorders of Consciousness/ The Vegetative State

Imagine you are at the bedside of a loved one who can’t speak, occasionally opens their eyes, yet gives no indication that they can understand you. To what degree, and for how long do you treat them as if they could? Are they really in there? And how could you ever know?

Brain injury and resulting disorders of consciousness aren’t new. But advances in science and medicine are revealing what was once unknowable. Hidden signs of cognition, and theories of covert conscious states are raising profound questions - questions that were once left to the divine.

Ancient civilizations have historically looked to divine explanations for what we today call “disorders of consciousness”. Today, we see people with severe brain injury as people who are sick, or disordered – Whereas in the past it was far more common to see things like coma and vegetative state as a part of the dying process. Before feeding tubes, ventilators, and modern hygiene, people with a severe brain injury very infrequently lasted as long as they do today. 

That being said, the understanding and treatment of coma and stroke, as well as various other neurological disorders, is documented as early as Ancient Mesopotamia. There are many preserved documents which indicate a class of specialists called āšipu who acted as priests and diagnosed certain illnesses or “evils” within the body. There were also specialists called ašu who focused more on medicinal remedies often in the form of herbs, animals, or mineral-amulets, as well as treating physical injuries.

The former specialist tended to deal with disorders of consciousness like coma, being that they were attributed to a malignant spirit known as alû. 

Diagnosis of coma was well documented, and many of the same physiological symptoms that we look for today, such as respiratory rate, reflexes, and eyes-opening were diligently recorded. 

Recorded in a medical text from mesopotamia, the āšipu state “If something like a stupor continually afflicts him and his limbs are tense, his ears roar and his mouth is ‘seized’ so that he cannot talk – the hand of an evil alû”

Treatments likely included some religious practices, but also consisted of evaluating the afflicted person’s response to noxious stimuli such as nasal tickling, or splashing water on their face. The patient’s response to these stimuli guided their prognoses – stating “ If he has been sick for 6 days and he does not get a respite on the seventh, they throw water on his face and he does not open his eyes - he will die. If he opens and closes his eyes at the water, they throw over him and wails-he will recover”

Though this is much less precise, and does not stem from any kind of understanding of the underlying physiological reasons for unconsciousness, it is very similar to what we do today in treating unconsciousness. Prognosis based on the level of response to stimuli is also a modern practice which can indicate to various degrees how well someone will recover from a coma.

Let’s fast forward. Skipping over the medieval era—a time when much of the progress in medicine and physiological reasoning gave way to magic, religion, and reliance on clerics and monks instead of physicians. And jumping instead to the Renaissance, we find a pivotal shift during the renaissance: a move away from supernatural explanations toward a focus on empirical evidence and critical observation. Along with revolutions in political thought, astronomy, art, and more, the renaissance brought new ideas about the unconscious.

Among many of the influential figures of the renaissance was Jacopo Berengario da Carpi, a physician who published the first illustrated anatomic textbook ever printed, titled “Commentaria cum amplissimis additionibus super anatomia mundini” which translates to “commentaries with extensive addition on Mundini’s Anatomy”. Mundini being a 14th century surgeon and medical teacher. Beyond his contributions to general anatomy, Berengario also authored a comprehensive treatise on head injuries where he detailed causes, symptoms and treatments for skull fractures, and injuries of the brain. 

This work, titled “Tractactis de Fractura Calvae sive Cranei”, described injuries like subdural hematomas, contrecoup lesions, and brain hemorrhages. His methods laid the groundwork for generations of physicians to come and widened the door for more empirical explorations of brain injury.

Other notable figures include:

 Guido Lanfranchi, who made early attempts to classify concussions as caused by a physiological reaction to shaking, as opposed to the spiritual explanation which existed previously.

Ambroise Pare championed scalp examination as a practice when dealing with brain injuries to assess skull fractures, a practice which is maintained today.

Renaissance thinkers like these radically altered the mechanisms that we attribute to brain injuries. From this point forward, science and medicine has progressed to attribute more and more disorders and illnesses of the brain to their underlying physical processes. 

The renaissance period laid the foundation for empirical inquiry into neurological disorders, but the understanding of disorders of consciousness was far from complete. It was not until the modern era that we began to systematically define and categorize these conditions.

The major turning point came in the 20th century with a seminal paper by Bryan Jennett and Fred Plum. This paper, published in 1972 introduced the concept of the persistent vegetative state (PVS). Jennett and Plum described PVS as a state of “wakeful unresponsiveness” characterized by open eyes and apparent wakefulness, but with no detectable awareness of the self or the environment. Importantly, their work made sure to acknowledge the limitations of bedside observations for these patients. After all, Plum was one of the first researchers to identify Locked-In state, and it was not lost on him that unresponsiveness is not necessarily an indication of unawareness. Plum in later years posed the central problem, being “we can only infer the self-awareness of others by their appearance and their acts”

Despite this, nosology of disorders of consciousness still relied exclusively on external observations such as motor responses, eye movements, and reflexes. Further categorizations in 1994 differentiated between persistent, and permanent, vegetative states. A persistent vegetative state being a condition that lasted longer than one month, while a permanent vegetative state indicated a prognosis of irreversibility. Typically, this permanent diagnosis was indicated after three months for anoxic injuries (injuries based on lack of oxygen to the brain), and twelve months for traumatic brain injuries.

Further categorization like this was important for predicting neurologic recovery, but did not speak much to what the afflicted person was experiencing. It wasn’t until the last 20 years or so that researchers have further differentiated unconscious disorders with their varied phenomenal states. That is, looking into “what it is like” to be in a coma, or vegetative state.

In 2002, a paper published in Neurology defined and reviewed diagnostic criteria for what was called “Minimally Conscious State” or MCS. This paper distinguished patients who demonstrated “inconsistent but discernible evidence of consciousness”. From here, specific diagnostic criteria for MCS was called for and some early behavioral signs were proposed. In later years, MCS has been refined to include MCS- which is lower in terms of awareness and predicted recovery, MCS+ which scores higher, and eMCS where predictive recovery and behavioral signs of consciousness are highest.

We are now caught up with the categorizations of disorders of consciousness, but there is still significant difficulty in making sure these diagnoses are correct. In the absence of consistent and reliable behavioral diagnostic tools, various imaging methods have been employed to aid diagnosis and single patient bedside treatment.

The first of these imaging methods was brain structural imaging. These methods,like MRI and CT typically aim to find large, anatomical pathologies. These methods are useful in finding things like hemorrhage, tumor, or other brain lesions, but prove to show “highly variable and heterogeneous findings in patients with DOC”, indicating that they are not a good diagnostic tool for DoC, and other neuroimaging techniques should be investigated.

The next functional imaging technique employed on DoC patients is the PET scan, or Positron Emission Tomography. PET scans assess brain activity by recording the emission of positrons from radioactively labeled molecules. Two different radioactive “labels” can be used. One which attaches to and follows the uptake of glucose in the brain, and another which follows blood flow.

What these preliminary PET scans showed is that stimuli presented to patients in VS/UWS were able to reach the patient’s primary sensory cortex, but any further communication with associative cortices was blocked. Cerebral communication with other “associative” cortices has been thought to be necessary for conscious perception when tested in healthy participants.

Contrastingly, MCS patients have been shown to have some cerebral communication to pain-related associative cortices when presented with noxious stimuli. This suggests that MCS patients, as opposed to VS/UWS patients, may have some capacity for conscious perception of pain or aversion.

The next functional imaging tool is fMRI or Functional Magnetic Resonance Imaging. fMRI relies on the magnetic properties of deoxyhemoglobin, a protein in your blood that has lost its oxygen. Active-task studies (meaning studies where the patient or participant is performing some sort of mental or motor task) have been used with this imaging technique to detect brain activity, but passive or resting-state fMRI has been employed increasingly for patients in DoC. This is because it doesn’t rely on patient participation which is useful in cases of DoC. fMRI provides many advantages such as spatial and temporal resolution (meaning the specific location of brain-data, and its changes in time are far more precise), but is also incompatible with any patients with devices like pacemakers, metallic implants, etc due to the magnetic pull of the machine. Despite these limitations, analysis and mapping of certain resting-state networks like the default mode network, auditory network, cerebellar network, visual network, and more, has taught us about the mechanism of cerebral communication, and has even suggested cause for some impairments in altered states of consciousness. 

For example, one study showed reduced intra network default mode network connectivity in patients with DoC. Essentially, a network in the brain that has been shown to be responsible for autobiographical memory recall, introspection, and other self-referential tasks, has been shown to be less active in patients with DoC. This, paired with other imaging that shows hyper-connectivity in structures of the limbic system may reflect a sort of “closed loop” architecture in patients with DoC, meaning that the impaired anatomical structure of the limbic system may be downregulating a network that is associated with self-reference and introspection. fMRI is an increasingly precise method of imaging, and when paired with machine learning based sorting paradigms, can be very helpful in distinguishing MCS patients from VS/UWS patients. The limitations of fMRI, such as cost, inaccessibility to patients with metal devices or implants, and the inability to utilize at the bedside, has pushed researchers to look at more clinically applicable methods like EEG or evoked potentials.

Electroencephalography, or EEG, measures the brain’s electrical activity in real time, offering a practical way to assess patient responses to stimulus, or resting state activity, at the bedside. Evoked potentials are brief electrical responses to stimuli, sort of like a time-focused EEG, looking at the latency of a response. Unlike fMRI or PET scans, EEG like this is relatively inexpensive, portable, and less restrictive for critically ill patients. Additionally, advances in digital signal processing, and machine learning, have made EEG-based detection of covert consciousness more realistic. 

Despite these advances in imaging and analysis, clinical care still grapples with profound ethical and social challenges regarding DoC patients. Debates over patient autonomy lack a precise grounding, and uncertainty in prognosis or phenomenology leads to both medical and familial disputes over treatment and end of life care.

One such dispute spanned more than a decade, bringing rarely discussed concepts such as consciousness, phenomenology, and the ethics of critical care – into the forefront of public debate.

The case of Terri Schiavo began in the winter of 1990. Then 26-year-old Terri Schiavo fell unconscious after suffering a cardiac arrest resulting from a span of disordered eating. Schiavo’s potassium levels were severely low. Low potassium or hypokalemia can result in serious cardiac abnormalities including sudden arrhythmia death syndrome. Following her collapse, her husband, Michael Sciavo, called emergency services but did not perform CPR. Terri was anoxic (lacking oxygen) until the paramedics arrived and administered CPR en route to the hospital.

Terri was stabilized in the hospital, but the prolonged period of anoxia caused severe brain damage. Shiavo stabilized into a persistent vegetative state with poor prognosis for any meaningful neurologic recovery. Months after her admission, computed tomography revealed severe atrophy of both cerebral hemispheres, and EEG showed no evidence of cortical activity. Experimental therapies including thalamic stimulation were administered, to no effect, for 3 years. At that point, her husband, acting with durable power of attorney, refused any further life sustaining measures on her behalf. Terri’s parents, Bob and Mary Schindler, did not accept the diagnosis of persistent vegetative state and opposed the ending of life-sustaining care. A legal battle ensued, leaving Terri Shiavo in a persistent vegetative state for 15 years before her death on March 31st 2005. The legal battle between Michael Schiavo and Bob and Mary Schindler brought to the public discourse questions about medical care for those with disorders of consciousness, and highlighted public misconceptions about those in a vegetative state. 

Terri’s parents argued that even small facial twitches or hand movements must reflect some sort of residual awareness. They collected video clips showing what appeared to the layman to be purposeful responses to their voices. They would show a video of an occasional smile or vocalization as a sign of some sort of meaningful, yet stifled interaction.

Neurologists, and other clinicians who were dealing with the case countered these observations, explaining that such movements were consistent with brainstem-mediated reflexes. The debate between Terri’s family and doctors was difficult to settle, and in the absence of absolute certainty as to the level of awareness in persistent vegetative state, Terri’s parents held on to hope that she may still recover, despite medical opinion.

Over time, the legal battle involved state and federal courts. Jeb Bush, then Governor of Florida even weighed in, signing emergency legislation into law that forced physicians to reinsert Terri’s feeding tube. This was following a petition by Michael Schiavo in 2001 to remove the feeding tube, which was granted by the Sixth Circuit Court in Florida. Michael maintained that Terri would not have wanted to live indefinitely in her condition. Numerous appeals and motions oscillated between various courts for years before finally in 2005, Terri’s feeding tube was permanently removed, and she died about two weeks later. An autopsy confirmed the severe and extensive nature of her brain injury. 

This case highlighted not only the inadequacies of existing legal guidelines in end of life care, but also demonstrated how arduous clinical treatment of those in vegetative state can be, particularly when the inner state of those affected is difficult to determine. 

As Medicine and science progress, and more data become available, cases like Terri’s are far less frequent. But the Terri Schiavo case underscores the central dilemma of disorders of consciousness; balancing uncertain clinical evidence with profound ethical and emotional stakes. It is why it is so important to continue to refine and increase our diagnostic tools for patients. From ancient rituals to advanced fMRI scans, the quest to detect, define, and dignify this boundary between awareness and unawareness continues.