Minimally conscious state
Encyclopedia
Minimally Conscious State (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. 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 112,000 to 280,000 in adult and pediatric cases.
” 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 different 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).
(MCS) is defined as a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.
Giacino et al. have suggested demonstration of the following behaviors in order to make the diagnosis of MCS.
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 suffered from traumatic brain injury
and those that suffered from non-traumatic brain injures (anoxia
, tumor
, hydrocephalus
, infection
). The patients were accessed 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 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 vegetative state non-traumatic brain injury group. Pairwise comparisons showed that DRS scores were significantly higher for those that suffered from non-tramuatic 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.
In summary, those with minimally conscious state
and non-traumatic brain injuries have a better chance of recovery than 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.
has been a relatively new criteria 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 those with conscious awareness (20-40% of normal ) 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.
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.
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.
(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.
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.
. There are currently multiple clinical trials underway investigating potential treatments.
In one case study, stimulation of thalamus using deep brain stimulation
(DBS) lead 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
.
In another case study of a 50 year old woman that 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. 45 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
agnoist. The fact that zolpidem
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
.
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. 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.
Persistent vegetative state
A persistent vegetative state is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. It is a diagnosis of some uncertainty in that it deals with a syndrome. After four weeks in a vegetative state , the patient is...
and Locked-in syndrome
Locked-In syndrome
Locked-in syndrome is a condition in which a patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes. Total locked-in syndrome is a version of locked-in syndrome where the eyes are paralyzed as...
. Unlike persistent vegetative state, patients with MCS have partial preservation of conscious awareness. 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 112,000 to 280,000 in adult and pediatric cases.
History
Prior to the mid 1990's, there was a lack of operational definitions available to clinicians and researchers to guide the differential diagnosis among disorder of consciousness. As a result, patients were lumped together into broad categories often based on the severity of the disability (eg. moderate, severe, extremely severe). These diagnosis were performed without regard to salient differences in behavioral and pathological characteristics. In a three year period spanning from 1994-1996, three position statements regarding the diagnostic criteria of disorder of consciousness were published. The “Medical Aspects of the Persistent Vegetative StatePersistent vegetative state
A persistent vegetative state is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. It is a diagnosis of some uncertainty in that it deals with a syndrome. After four weeks in a vegetative state , the patient is...
” was published by
the American Academy of Neurology
American Academy of Neurology
The American Academy of Neurology is a professional society for neurologists and neuroscientists. As a medical specialty society it was established in 1949 by A.B. Baker of the University of Minnesota to advance the art and science of neurology, and thereby promote the best possible care for...
(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
American Congress of Rehabilitation Medicine
The American Congress of Rehabilitation Medicine is an organization of rehabilitation professionals dedicated to serving people with disabling conditions by supporting research that:...
(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
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
, rehabilitation
Rehabilitation
-Mental health:* Drug rehabilitation* Rehabilitation , the rehabilitation of criminal behavior.* Rehabilitation , therapy aimed at improving neurocognitive function that has been lost or diminished by disease or traumatic injury...
, neurosurgery
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
, and neuropsychology
Neuropsychology
Neuropsychology studies the structure and function of the brain related to specific psychological processes and behaviors. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied to efforts to record electrical activity from individual cells in...
. However, because the diagnostic criteria were published independently from one another, the final recommendations different 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
Minimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
(MCS).
Medical Definition
Minimally conscious stateMinimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
(MCS) is defined as a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.
Diagnosis
Although MCS patients are able to demonstrate cognitively mediated behavior, 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 (eg. a finger movement or a blink) occurred because of a specific environmental event (eg. a command to move the finger or to blink) or was merely a coincidental behavior. 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.Giacino et al. have suggested demonstration of the following behaviors in order to make the diagnosis of MCS.
- Following simple commands.
- Gestural or verbal yes/no responses (regardless of accuracy).
- Intelligible verbalization.
- Purposeful behavior such as those that are contingent due to appropriate environmental stimuli and are not reflexive. Some examples of purposeful behavior include:
- appropriate smiling or crying in response to the linguistic or visual content of emotional but not to neutral topics or stimuli.
- vocalizations or gestures that occur in direct response to the linguistic content of questions.
- reaching for objects that demonstrates a clear relationship between object location and direction of reach.
- touching or holding objects in a manner that accommodates the size and shape of the object.
- pursuit eye movement or sustained fixation that occurs in direct response to moving or salient stimuli.
Prognosis
One of the defining characteristics of minimally conscious stateMinimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
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
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
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 suffered from traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
and those that suffered from non-traumatic brain injures (anoxia
Anoxia
The term anoxia means a total decrease in the level of oxygen, an extreme form of hypoxia or "low oxygen". The terms anoxia and hypoxia are used in various contexts:* Anoxic waters* Anoxic event* Dead zone or hypoxic zones...
, tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
, hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
, infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
). The patients were accessed 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 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 vegetative state non-traumatic brain injury group. Pairwise comparisons showed that DRS scores were significantly higher for those that suffered from non-tramuatic 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.
In summary, those with minimally conscious state
Minimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
and non-traumatic brain injuries have a better chance of recovery than 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.
Neuroimaging
Because minimally conscious stateMinimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
has been a relatively new criteria 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 those with conscious awareness (20-40% of normal ) and is slightly higher but comparable to those in vegetative states. Activation in the medial parietal cortex and adjacent posterior cingulate cortex
Cingulate cortex
The cingulate cortex is a part of the brain situated in the medial aspect of the cortex. It includes the cortex of the cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cingulate sulcus...
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
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
, hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
state, dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, 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
Temporal
Temporal can refer to:* of or relating to time** Temporality in philosophy** Temporal database, a database recording aspects of time varying values** The Temporal power of the Popes of the Roman Catholic Church...
and prefrontal cortices in MCS than vegetative states. These findings encourage treatments based on neuromodulatory and cognitive revalidation therapeutic strategies for patients with MCS.
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
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....
were increased in size, and the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
and the periventricular white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
were diminished. The DTI maps showed that there was significant reduction of volume in the medial corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
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
Minimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
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
Neuroplasticity
Neuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
in both brain structure and function following severe injuries. Utilizing DTI and other neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
techniques may further shed light on the debates on long-distance cortical rewiring and may lead to better rehabilitation strategies.
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
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) scans found increased blood flow to the secondary sensory cortex, posterior parietal cortex, premotor cortex
Premotor cortex
The premotor cortex is an area of motor cortex lying within the frontal lobe of the brain. It extends 3 mm anterior to the primary motor cortex, near the Sylvian fissure, before narrowing to approximately 1 mm near the medial longitudinal fissure, which serves as the posterior border for...
, 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
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
, 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.
Residual Language Function
A functional magnetic resonance imagingFunctional magnetic resonance imaging
Functional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used to measure the hemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of neuroimaging...
(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.
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.
Treatment
There is currently no definitive evidence that support altering the course of the recovery of minimally conscious stateMinimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
. There are currently multiple clinical trials underway investigating potential treatments.
In one case study, stimulation of thalamus using deep brain stimulation
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
(DBS) lead 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
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
. 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
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
showed that the patient's global cerebral metabolism levels were markedly reduced. He had DBS electrodes implanted bilaterally within his central thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
. 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
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
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
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
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
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
regions. This pathway is crucial for many executive functions
Executive functions
The executive system is a theorized cognitive system in psychology that controls and manages other cognitive processes. It is responsible for processes that are sometimes referred to as the executive function, executive functions, supervisory attentional system, or cognitive control...
such as working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...
, effort regulation, selective attention, and focus
Focus
Focus, FOCUS, or foci may refer to:In science, mathematics or computing:*Focus , selectively concentrating on one aspect of the environment while ignoring other things...
.
In another case study of a 50 year old woman that had symptoms consistent with MCS, administration of zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
, a sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
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. 45 minutes after 5 to 10 mg of zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
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
PET
-Medicine:* Patulous Eustachian tube, a medical disorder affecting the middle ear* Positron emission tomography or PET, a medical imaging technique* Pre-eclampsia, a medical complication of pregnancy-Science:...
scans showed that after zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
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
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
. These areas are thought to have been inhibited by the site of injury through a GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
-mediated mechanism and the inhibition was modified by zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
which is a GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
agnoist. The fact that zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
a sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
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
.
Ethical Issues
One of the major ethical concerns involving patients with severe brain damage is their inability to communicate. Be definition, patients that 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.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 SchiavoTerri Schiavo
The Terri Schiavo case was a legal battle in the United States between the legal guardians and the parents of Teresa Marie "Terri" Schiavo that lasted from 1998 to 2005...
who was diagnosed with persistent vegetative state
Persistent vegetative state
A persistent vegetative state is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. It is a diagnosis of some uncertainty in that it deals with a syndrome. After four weeks in a vegetative state , the patient is...
. In the case of minimally conscious state
Minimally conscious state
Minimally Conscious State 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. MCS is a relatively new category of disorders of consciousness. The...
patients, they are neither permanently unconscious nor are they necessarily hopelessly damaged. Thus, these patients warrant additional evaluation. 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.