Minimally conscious state

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Minimally Conscious State
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Brain scans of various disorders of consciousness, including minimally conscious state

A minimally conscious state or MCS is a disorder of consciousness distinct from persistent vegetative state and locked-in syndrome. Unlike persistent vegetative state, patients with MCS have partial preservation of conscious awareness. [1] MCS is a relatively new category of disorders of consciousness. The natural history and longer term outcome of MCS have not yet been thoroughly studied. The prevalence of MCS was estimated to be 9 times of PVS cases (adult and pediatric), or between 112,000 and 280,000 in the US by year 2000. [2]

Contents

Pathophysiology

Neuroimaging

Because minimally conscious state is a relatively new criterion for diagnosis, there are very few functional imaging studies of patients with this condition. Preliminary data has shown that overall cerebral metabolism is less than in those with conscious awareness (20–40% of normal [3] ) and is slightly higher but comparable to those in vegetative states. Activation in the medial parietal cortex and adjacent posterior cingulate cortex are brain regions that seem to differ between patients in MCS and those from vegetative states. These areas are most active during periods of conscious waking and are least active when in altered states of consciousness, such as general anesthesia, propofol, hypnotic state, dementia, and Wernicke–Korsakoff syndrome. Auditory stimulation induced more widespread activation in the primary and pre-frontal associative areas of MCS patients than vegetative state patients. There were also more cortiocortical functional connectivity between the auditory cortex and a large network of temporal and prefrontal cortices in MCS than vegetative states. These findings encourage treatments based on neuromodulatory and cognitive revalidation therapeutic strategies for patients with MCS. [4]

Resting overall cerebral metabolism of various brain states. Neurowiki 1.GIF
Resting overall cerebral metabolism of various brain states.
Arousal levels of various brain states. Neurowiki2.gif
Arousal levels of various brain states.

One study used diffusion tensor imaging (DTI) in two case studies. They found that there were widespread cerebral atrophy in both patients. The lateral ventricles were increased in size, and the corpus callosum and the periventricular white matter were diminished. The DTI maps showed that there was significant reduction of volume in the medial corpus callosum and other parts of the brain compared to normal subjects. They also found markedly lower diffusion values in white matter and increased cerebral spinal fluid compartments. Cortical injuries at this level provides a particular favorable environment for sprouting of new axons to occur in the intact areas of the cortex, which may explain some of the greater recovery rates in minimally conscious state patients. The axonal regrowth has been correlated with functional motor recovery. The regrowth and rerouting of the axons may explain some of the changes to brain structure. These findings support the efforts to prospectively and longitudinally characterize neuroplasticity in both brain structure and function following severe injuries. Utilizing DTI and other neuroimaging techniques may further shed light on the debates on long-distance cortical rewiring and may lead to better rehabilitation strategies. [5]

Some areas of the brain that are correlated with the subjective experience of pain were activated in MCS patients when noxious stimulation was present. Positron emission tomography (PET) scans found increased blood flow to the secondary sensory cortex, posterior parietal cortex, premotor cortex, and the superior temporal cortex. The pattern of activation, however, was with less spatial extent. Some parts of the brain were less activated than normal patients during noxious stimulus processing. These were the posterior cingulate, medial prefrontal cortex, and the occipital cortex. Even though functional brain imaging can objectively measure changes in brain function during noxious stimulation, the role of different areas of the brain in pain processing is only partially understood. Furthermore, there is still the problem of the subjective experience. MCS patients by definition cannot consistently and reliably communicate their experiences. Even if they were able to answer the question "are you in pain?", there would not be a reliable response. Further clinical trials are needed to access the appropriateness of the use of analgesia in patients with MCS. [6]

Residual language function

A functional magnetic resonance imaging (fMRI) study found that minimally conscious state patients showed activation in auditory networks when they heard narratives that had personally meaningful content that were read forwards by a familiar voice. These activations were not seen when the narratives were read backwards. [7]

Another study compared patients in vegetative state and minimally conscious state in their ability to recognize language. They found that some patients in minimally conscious state demonstrated some evidence of preserved speech processing. There was more activation in response to sentences compared to white noise. [8]

Diagnostic

Medical definition

Minimally conscious state (MCS) is defined as a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated. [1]

Diagnosis

Although MCS patients are able to demonstrate cognitively mediated behaviors, they occur inconsistently. They are, however, reproducible or can be sustained long enough to be differentiated from reflexive behavior. Because of this inconsistency, extended assessment may be required to determine if a simple response (e.g. a finger movement or a blink) occurred because of a specific environmental event (e.g. a command to move the finger or to blink) or was merely a coincidental behavior. [1] Distinguishing between VS and MCS is often difficult because the diagnosis is dependent on observation of behavior that show self or environmental awareness and because those behavioral responses are markedly reduced. One of the more common diagnostic errors involving disorders of consciousness is mistaking MCS for VS which may lead to serious repercussions related to clinical management. [9]

Giacino et al. have suggested demonstration of the following behaviors in order to make the diagnosis of MCS.

Treatment

There is currently no definitive evidence that support altering the course of the recovery of minimally conscious state. There are currently multiple clinical trials underway investigating potential treatments. [11] In one case study, stimulation of thalamus using deep brain stimulation (DBS) led to some behavioral improvements. The patient was a 38-year-old male who had remained in minimally conscious state following a severe traumatic brain injury. He had been unresponsive to consistent command following or communication ability and had remained non-verbal over two years in inpatient rehabilitation. fMRI scans showed preservation of a large-scale, bi-hemispheric cerebral language network, which indicates that possibility for further recovery may exist. Positron emission tomography showed that the patient's global cerebral metabolism levels were markedly reduced. He had DBS electrodes implanted bilaterally within his central thalamus. More specifically, the DBS electrodes targeted the anterior intralaminar nuclei of thalamus and adjacent paralaminar regions of thalamic association nuclei. Both electrodes were positioned within the central lateral nucleus, the paralaminar regions of the median dorsalis, and the posterior-medial aspect of the centromedian/parafasicularis nucleus complex. This allowed maximum coverage of the thalamic bodies. A DBS stimulation was conducted such that the patient was exposed to various patterns of stimulation to help identify optimal behavioral responses. Approximately 140 days after the stimulation began, qualitative changes in behavior emerged. There were longer periods of eye opening and increased responses to command stimuli as well as higher scores on the JFK coma recovery scale (CRS). Functional object use and intelligible verbalization was also observed. The observed improvements in arousal level, motor control, and consistency of behavior could be a result of direct activation of frontal cortical and basal ganglia systems that were innervated by neurons within the thalamic association nuclei. These neurons act as a key communication relay and form a pathway between the brainstem arousal systems and frontal lobe regions. This pathway is crucial for many executive functions such as working memory, effort regulation, selective attention, and focus. [12]

In another case study of a 50-year-old woman who had symptoms consistent with MCS, administration of zolpidem, a sedative hypnotic drug improved the patient's condition significantly. Without treatment, the patient showed signs of mutism, athetoid movements of the extremities, and complete dependence for all personal care. Forty-five minutes after 5 to 10 mg of zolpidem was administered, the patient ceased the athetoid movements, regained speaking ability, and was able to self-feed. The effect lasted 3–4 hours from which she returned to the former state. The effects were repeated on a daily basis. PET scans showed that after zolpidem was administered, there was a marked increase in blood flow to areas of the brain adjacent to or distant from damaged tissues. In this case, these areas were the ipsilateral cerebral hemispheres and the cerebellum. These areas are thought to have been inhibited by the site of injury through a GABA-mediated mechanism and the inhibition was modified by zolpidem which is a GABA agonist. The fact that zolpidem is a sedative drug that induces sleep in normal people but causes arousal in a MCS patient is paradoxical. The mechanisms to why this effect occurs is not entirely clear. [13]

There is recent evidence that transcranial direct current stimulation (tDCS), a technique that supplies a small electric current in the brain with non-invasive electrodes, may improve the clinical state of patients with MCS. In one study with 10 patients with disorders of consciousness (7 in VS, 3 in MCS), tDCS was applied for 20 minutes every day for 10 days, and showed clinical improvement in all 3 patients who were in MCS, but not in those with VS. These results remained at 12-month follow-up. Two of the patients in MCS that had their brain insult less than 12 months recovered consciousness in the following months. One of these patients received a second round of tDCS treatment 4 months after his initial treatment, and showed further recovery and emerged into consciousness, with no change of clinical status between the two treatments. [14]

Prognosis

One of the defining characteristics of minimally conscious state is the more continuous improvement and significantly more favorable outcomes post injury when compared with vegetative state. One study looked at 100 patients with severe brain injury. At the beginning of the study, all the patients were unable to follow commands consistently or communicate reliably. These patients were diagnosed with either MCS or vegetative state based on performance on the JFK Coma Recovery Scale and the diagnostic criteria for MCS as recommended by the Aspen Consensus Conference Work-group. Both patient groups were further separated into those that had traumatic brain injury and those that had non-traumatic brain injures (anoxia, tumor, hydrocephalus, infection). The patients were assessed multiple times over a period of 12 months post injury using the Disability Rating Scale (DRS) which ranges from a score of 30=dead to 0=no disabilities. The results show that the DRS scores for the MCS subgroups showed the most improvement and predicted the most favorable outcomes 12 months post injury. Amongst those diagnosed with MCS, DRS scores were significantly lower for those with non-traumatic brain injuries in comparison to the vegetative state patients with traumatic brain injury. DRS scores were also significantly lower for the MCS non-traumatic brain injury group compared to the MCS traumatic brain injury group. Pairwise comparisons showed that DRS scores were significantly higher for those that suffered from non-traumatic brain injuries than those with traumatic brain injuries. For the patients in vegetative states there were no significant differences between patients with non-traumatic brain injury and those with traumatic brain injuries. Out of the 100 patients studied, 3 patients fully recovered (had a DRS score of 0). These 3 patients were diagnosed with MCS and had suffered from traumatic brain injuries. [9]

In summary, those with minimally conscious state and non-traumatic brain injuries will not progress as well as those with traumatic brain injuries while those in vegetative states have an all around lower to minimal chance of recovery.

Because of the major differences in prognosis described in this study, this makes it crucial that MCS be diagnosed correctly. Incorrectly diagnosing MCS as vegetative state may lead to serious repercussions related to clinical management.

History

Prior to the mid-1990s, there was a lack of operational definitions available to clinicians and researchers to guide the differential diagnosis among disorders of consciousness. As a result, patients were lumped together into broad categories often based on the severity of the disability (e.g. moderate, severe, extremely severe). These diagnoses were performed without regard to salient differences in behavioral and pathological characteristics. In a three-year period spanning from 1994 to 1996, three position statements regarding the diagnostic criteria of disorder of consciousness were published. The "Medical Aspects of the Persistent Vegetative State" was published by the American Academy of Neurology (AAN) in 1994. In 1995, "Recommendations for Use of Uniform Nomenclature Pertinent to Patients With Severe Alterations in Consciousness" was published by the American Congress of Rehabilitation Medicine (ACRM). In 1996 the "International Working Party on the Management of the Vegetative State: Summary Report" was published by a group of international delegates from neurology, rehabilitation, neurosurgery, and neuropsychology. However, because the diagnostic criteria were published independently from one another, the final recommendations differed greatly from one another. The Aspen Neurobehavioral Work-group was convened to explore the underlying causes of these disparities. In the end, the Aspen Work-group provided a consensus statement regarding definitions and diagnostic criteria disorder of consciousness which include the vegetative state (VS) and the minimally conscious state (MCS). [15]

Ethical issues

One of the major ethical concerns involving patients with severe brain damage is their inability to communicate. By definition, patients who are unconscious or are minimally conscious are incapable of giving informed consent which is required for participation in clinical research. Typically, written approval is obtained from family members or legal representatives. The inability to receive informed consent has led to much research being refused grants, ethics committee approval, or research publication. This puts patients in these conditions at risk of being denied therapy that may be life-saving. [4]

The right to die

The right to die in patients with severe cognitive impairment has developed over time because of their grave neurological state and the perceived futility of continued treatment. Such cases have been debated vigorously in the past, as in the case with Terri Schiavo who was diagnosed with persistent vegetative state. In the case of minimally conscious state patients, they are neither permanently unconscious nor are they necessarily hopelessly damaged. Thus, these patients warrant additional evaluation. [16] On one hand, some argue that entertaining the possibility of intervention in some patients may erode the "right to die" moral obligation. Conversely, there is also fear that people may associate attitudes with higher-functioning people in minimally conscious state with people in persistent vegetative state, thus minimizing the value of their lives. [17]

Regulating therapeutic nihilism

Currently, risk aversion dominates the ethical landscape when research involves those with impaired decision-making abilities. [16] Fears of therapeutic adventurism has led to a disproportionate view about the under-appreciation of potential benefits and an overstatement of risks[ clarification needed ]. Thus, recognizing this distortion is important in order to calculate the right balance between protecting vulnerable populations that cannot provide autonomous consent and potentially restorative clinical trials. [16]

Notable examples

Related Research Articles

<span class="mw-page-title-main">Coma</span> State of unconsciousness

A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. The person may experience respiratory and circulatory problems due to the body's inability to maintain normal bodily functions. People in a coma often require extensive medical care to maintain their health and prevent complications such as pneumonia or blood clots. Coma patients exhibit a complete absence of wakefulness and are unable to consciously feel, speak or move. Comas can be derived by natural causes, or can be medically induced.

<span class="mw-page-title-main">Head injury</span> Serious trauma to the cranium

A head injury is any injury that results in trauma to the skull or brain. The terms traumatic brain injury and head injury are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of injuries, there are many causes—including accidents, falls, physical assault, or traffic accidents—that can cause head injuries.

<span class="mw-page-title-main">Transcranial magnetic stimulation</span> Form of brain stimulation using magnetic fields

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil connected to the scalp. The stimulator generates a changing electric current within the coil which creates a varying magnetic field, inducing a current within a region in the brain itself.

<span class="mw-page-title-main">Locked-in syndrome</span> Condition in which a patient is aware but completely paralysed

Locked-in syndrome (LIS), also known as pseudocoma, is a condition in which a patient is aware but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for vertical eye movements and blinking. The individual is conscious and sufficiently intact cognitively to be able to communicate with eye movements. Electroencephalography results are normal in locked-in syndrome. Total locked-in syndrome, or completely locked-in state (CLIS), is a version of locked-in syndrome wherein the eyes are paralyzed as well. Fred Plum and Jerome B. Posner coined the term for this disorder in 1966.

Alien hand syndrome (AHS) or Dr. Strangelove syndrome is a category of conditions in which a person experiences their limbs acting seemingly on their own, without conscious control over the actions. There are a variety of clinical conditions that fall under this category, which most commonly affects the left hand. There are many similar terms for the various forms of the condition, but they are often used inappropriately. The affected person may sometimes reach for objects and manipulate them without wanting to do so, even to the point of having to use the controllable hand to restrain the alien hand. Under normal circumstances however, given that intent and action can be assumed to be deeply mutually entangled, the occurrence of alien hand syndrome can be usefully conceptualized as a phenomenon reflecting a functional "disentanglement" between thought and action.

A vegetative state (VS) or post-coma unresponsiveness (PCU), is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative state, the patient is classified as being in a persistent vegetative state (PVS). This diagnosis is classified as a permanent vegetative state some months after a non-traumatic brain injury or one year after a traumatic injury. The term unresponsive wakefulness syndrome may be alternatively used, as "vegetative state" has some negative connotations among the public.

<span class="mw-page-title-main">Brain damage</span> Destruction or degeneration of brain cells

Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage.

Anosognosia is a condition in which a person with a disability is cognitively unaware of having it due to an underlying physical condition. Anosognosia results from physiological damage to brain structures, typically to the parietal lobe or a diffuse lesion on the fronto-temporal-parietal area in the right hemisphere, and is thus a neuropsychiatric disorder. A deficit of self-awareness, it was first named by the neurologist Joseph Babinski in 1914.

In philosophy and neuroscience, neuroethics is the study of both the ethics of neuroscience and the neuroscience of ethics. The ethics of neuroscience concerns the ethical, legal and social impact of neuroscience, including the ways in which neurotechnology can be used to predict or alter human behavior and "the implications of our mechanistic understanding of brain function for society... integrating neuroscientific knowledge with ethical and social thought".

Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.

<span class="mw-page-title-main">Traumatic brain injury</span> Injury of the brain from an external source

A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumatic brain injury. TBI can also be characterized based on mechanism or other features. Head injury is a broader category that may involve damage to other structures such as the scalp and skull. TBI can result in physical, cognitive, social, emotional and behavioral symptoms, and outcomes can range from complete recovery to permanent disability or death.

Closed-head injury is a type of traumatic brain injury in which the skull and dura mater remain intact. Closed-head injuries are the leading cause of death in children under 4 years old and the most common cause of physical disability and cognitive impairment in young people. Overall, closed-head injuries and other forms of mild traumatic brain injury account for about 75% of the estimated 1.7 million brain injuries that occur annually in the United States. Brain injuries such as closed-head injuries may result in lifelong physical, cognitive, or psychological impairment and, thus, are of utmost concern with regards to public health.

<span class="mw-page-title-main">Temporal lobe epilepsy</span> Chronic focal seizure disorder

In the field of neurology, temporal lobe epilepsy is an enduring brain disorder that causes unprovoked seizures from the temporal lobe. Temporal lobe epilepsy is the most common type of focal onset epilepsy among adults. Seizure symptoms and behavior distinguish seizures arising from the medial temporal lobe from seizures arising from the lateral (neocortical) temporal lobe. Memory and psychiatric comorbidities may occur. Diagnosis relies on electroencephalographic (EEG) and neuroimaging studies. Anticonvulsant medications, epilepsy surgery and dietary treatments may improve seizure control.

<span class="mw-page-title-main">Frontal lobe disorder</span> Brain disorder

Frontal lobe disorder, also frontal lobe syndrome, is an impairment of the frontal lobe of the brain due to disease or frontal lobe injury. The frontal lobe plays a key role in executive functions such as motivation, planning, social behaviour, and speech production. Frontal lobe syndrome can be caused by a range of conditions including head trauma, tumours, neurodegenerative diseases, neurodevelopmental disorders, neurosurgery and cerebrovascular disease. Frontal lobe impairment can be detected by recognition of typical signs and symptoms, use of simple screening tests, and specialist neurological testing.

Memory and trauma is the deleterious effects that physical or psychological trauma has on memory.

Post-traumatic amnesia (PTA) is a state of confusion that occurs immediately following a traumatic brain injury (TBI) in which the injured person is disoriented and unable to remember events that occur after the injury. The person may be unable to state their name, where they are, and what time it is. When continuous memory returns, PTA is considered to have resolved. While PTA lasts, new events cannot be stored in the memory. About a third of patients with mild head injury are reported to have "islands of memory", in which the patient can recall only some events. During PTA, the patient's consciousness is "clouded". Because PTA involves confusion in addition to the memory loss typical of amnesia, the term "post-traumatic confusional state" has been proposed as an alternative.

<span class="mw-page-title-main">Neural correlates of consciousness</span> Neuronal events sufficient for a specific conscious percept

The neural correlates of consciousness (NCC) refer to the relationships between mental states and neural states and constitute the minimal set of neuronal events and mechanisms sufficient for a specific conscious percept. Neuroscientists use empirical approaches to discover neural correlates of subjective phenomena; that is, neural changes which necessarily and regularly correlate with a specific experience. The set should be minimal because, under the materialist assumption that the brain is sufficient to give rise to any given conscious experience, the question is which of its components are necessary to produce it.

Traumatic brain injury can cause a variety of complications, health effects that are not TBI themselves but that result from it. The risk of complications increases with the severity of the trauma; however even mild traumatic brain injury can result in disabilities that interfere with social interactions, employment, and everyday living. TBI can cause a variety of problems including physical, cognitive, emotional, and behavioral complications.

<span class="mw-page-title-main">Steven Laureys</span> Belgian neurologist (born 1968)

Steven Laureys is a Belgian neurologist. He is principally known as a clinician and researcher in the field of neurology of consciousness.

Disorders of consciousness are medical conditions that inhibit consciousness. Some define disorders of consciousness as any change from complete self-awareness to inhibited or absent self-awareness and arousal. This category generally includes minimally conscious state and persistent vegetative state, but sometimes also includes the less severe locked-in syndrome and more severe but rare chronic coma. Differential diagnosis of these disorders is an active area of biomedical research. Finally, brain death results in an irreversible disruption of consciousness. While other conditions may cause a moderate deterioration or transient interruption of consciousness, they are not included in this category.

References

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  2. ↑ Strauss, DJ; Ashal S; Day SM; et al. (2000). "Life expectancy of children in vegetative and minimally conscious states". Pediatric Neurology. 23 (4): 1–8. CiteSeerX   10.1.1.511.2986 . doi:10.1016/S0887-8994(00)00194-6. PMID   11068163.
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  5. ↑ Voss, H. U.; Uluç, A. M.; Dyke, J. P.; Watts, R.; Kobylarz, E. J.; McCandliss, B. D.; Heier, L. A.; Beattie, B. J.; Hamacher, K. A.; Vallabhajosula, S.; Goldsmith, S. J.; Ballon, D.; Giacino, J. T.; Schiff, N. D. (2006). "Possible axonal regrowth in late recovery from the minimally conscious state". Journal of Clinical Investigation. 116 (7): 2005–2011. doi:10.1172/JCI27021. PMC   1483160 . PMID   16823492.
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  9. 1 2 Giacino, JT; Kalmar K (1997). "The Vegetative and Minimally Conscious States: A comparison of Clinical Features and Functional Outcome". J Head Trauma Rehabil. 12 (4): 36–51. doi:10.1097/00001199-199708000-00005. S2CID   56947267.
  10. ↑ Panda, R.; Thibaut, A.; Lopez-Gonzalez, A.; Escrichs, A.; Bahri, M. A.; Hillebrand, A.; Deco, G.; Laureys, S.; Gosseries, O.; Annen, J.; Tewarie, P. (September 25, 2022). "Exploring the Mechanisms Underlying Disorders of Consciousness". eLife. 11. doi: 10.7554/eLife.77462 . PMC   9385205 . PMID   35916363 . Retrieved October 1, 2022.
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  13. ↑ Shames, J. L.; Ring, H. (2008). "Transient Reversal of Anoxic Brain Injury−Related Minimally Conscious State After Zolpidem Administration: A Case Report". Archives of Physical Medicine and Rehabilitation. 89 (2): 386–388. doi:10.1016/j.apmr.2007.08.137. PMID   18226667.
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  16. 1 2 3 Fins JJ (April 2003). "Constructing an ethical stereotaxy for severe brain injury: balancing risks, benefits and access". Nature Reviews Neuroscience. 4 (4): 323–327. doi:10.1038/nrn1079. PMID   12671648. S2CID   4341629.
  17. ↑ Coleman, D (2002). "The minimally conscious state: definition and diagnostic criteria". Neurology. 58 (3): 506–507. doi:10.1212/wnl.58.3.506. PMID   11839872.
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