Disorders of consciousness

Disorders of consciousness (DoC) are a group of complex and rare neurological conditions with an important impact on healthcare systems. Our imperfect understanding of the neural correlates underlying consciousness itself and the conflicting theories on the mechanisms responsible for its alterations complicate the establishment of consensual diagnostic and therapeutic guidelines. Yet the clinician confronted with brain-injured patients must adopt care strategies and make ethical decisions that often determine life and death.

Coma

Unresponsivess and acute care

Acute loss of consciousness after brain injury can result either spontaneously from dysfunctions directly related to the neural damage (e.g., in traumatic brain injury - TBI) and insufficient blood supply to the brain (e.g., in cardiac arrest), or from sedatives administered to the patient by healthcare staff. Coma is defined as a state of prolonged unarousable unconsciousness with absence of both wakefulness and awareness signs, featuring a total absence of reaction to external (auditory, visual, noxious) stimuli. A comatose patient is therefore unable to perform spontaneous movements, display any form of voluntary behavior or vocalizations. A score below 8 in the Glasgow Coma Scale (GCS) is sometimes erroneously considered to be indicative of coma in clinical units and commonly thought to warrant endotracheal intubation, although this threshold should correctly denote a “severe injury”, and there is no evidence to recommend systematic intubation upon arrival for these patients. A minimum duration of one hour is usually used to disentangle coma from shorter losses of consciousness such as syncope or seizures. When coma is not related to the administration of sedative agents, it usually denotes an impairment of brainstem structures responsible for maintaining arousal, in particular the ascending reticular activating system.

Whether the loss of consciousness is spontaneous or not, most patients with severe brain injury will receive anesthetics and undergo a transient period of artificial coma to allow the stabilization of hemodynamic function, avoid pain, facilitate mechanical assisted ventilation, carry out necessary surgical operations (e.g., decompressive craniectomy), and optimize electrolytic, metabolic, hepatic, renal and hormonal function, among other confounding factors. Sedation can also serve neurological specific indications, as it reduces the brain’s metabolic rates and its tolerance to ischemia, possibly limiting the extent of brain injury, it drives intracranial pressure down, which can be life-saving for patients with intracranial hypertension, and it decreases seizure rates. On the other hand, the use of minimal sedation and daily sedation interruptions has proven to yield better outcomes in the ICU for critically ill patients of other causes, reducing mortality, length of stay, duration of ventilation, nosocomial infections and costs. The choice of the sedative agent can also have an impact on the profile of adverse effects, the length and depth of sedation, the effectiveness against status epilepticus or the ease to wean mechanical ventilation. Propofol and midazolam are currently considered first-line agents for patients with severe acquired brain injury and are the most widely used in neuro ICUs, while alternatives such as ketamine or dexmedetomidine can be indicated in specific cases. The management of comatose patients with severe brain injury in the neurological ICU must therefore take into account an intricate set of risk and benefits regarding sedation in the acute phase.

Unresponsive wakefulness syndrome

Responsive yet unaware

Most of the remaining patients will recover signs of wakefulness shortly after withdrawal of sedation, by opening their eyes or demonstrating vegetative nervous system activity. This condition of preserved arousal despite the complete absence of clinical signs of awareness has taken many names throughout the development of modern neurology. If the terms of “coma vigile” and “apallic syndrome” are now outdated, the vegetative state (VS) is the most commonly used title outside of Europe. This term coined by Jennett and Plum in 1972 as a reference to the vegetative nervous system which is preserved in this syndrome, contrasting with the unresponsiveness of the higher cognitive functions located in the central nervous system. Indeed, patients in this pathological state can display preserved sleep-wake cycles, normal homeostatic functions and reflexive behaviors, such as eye movements, limb flexion, lip movements, tooth grinding or yawning. Yet, they are unable to exhibit voluntary behaviors or oriented responses to external prompts, whether tactile, noxious, visual or auditory. The “persistent vegetative state” defines patients after 1 month in VS, while the “permanent vegetative state” was used for patients in VS after 3 months in the US and 6 months in the UK for non-traumatic injury, and after 12 months for traumatic injuries. Given the rare but confirmed reports of late recovery after several years in VS, the latest guidelines recommend the elimination of this term in favor of the “chronic vegetative state” which makes less prognostic assumptions. In the UK, the term “prolonged DOC” is defined as reduced consciousness for more than four weeks after brain injury, and can therefore partially overlap with the other terminologies. Besides, another terminology has been proposed to address the negative connotation associated with the term “vegetative”, as it can be erroneously perceived by caregivers to refer to a “vegetal” or “vegetable”. The unresponsive wakefulness syndrome (UWS) uses a more descriptive wording to refer to the VS. It also leaves room for possible residual brain functions in behaviorally non-responsive patients, as recently demonstrated by neuroimaging studies on cognitive motor dissociation. This taxonomy has been more popular in Europe so far, while northern American guidelines recommend the use of both terms, as the advantages of both systems and their perceived value are still an active subject of controversy.

Minimally conscious state

Recovery of awareness

 The minimally conscious state (MCS) has been formulated more recently to provide a common diagnostic entity for patients who could recover signs of conscious awareness in addition to wakefulness. These behaviors can fluctuate and be strongly limited in amplitude by motor or cognitive constraints, but they must be unequivocal and reproducible. The patients however remain unable to functionally communicate by any possible means, and their interaction with the external environment is therefore strongly limited. An initial list of behaviors that warrant the presence of conscious processing and define the MCS has been established and used as basis for the constitution of the CRS-R. It is still currently used in clinical practice, but additional behaviors have been proposed to be added to these diagnostic criteria. As the MCS includes very heterogeneous subgroups of patients, ranging from those barely able to localize a painful stimulation, to those able to follow simple commands and produce intelligible words, studying their prognostic trajectories and offering treatment directives may reveal challenging or inaccurate. To address this issue, a subcategorization of the MCS has been proposed, where the MCS “minus” (MCS-) would concern patients able to demonstrate low-level language-independent signs of consciousness (visual fixation, visual pursuit, localization to pain, oriented movements) and the MCS “plus” (MCS+) would define patients who show higher-level language-related behaviors (command-following, intelligible verbalization, intentional communication). The patients in MCS have demonstrated better outcomes than those in UWS, as the MCS can be a transient intermediate state towards emergence and functional recovery, but long-lasting cases of MCS are also frequent and it can be a chronic disease.

Emergence from minimally conscious state

Recovery of functional communication

When patients are able to functionally communicate, either through verbal interaction, a communication code or assistive technology, or when they are able to functionally use common items, such as a pen or a comb, they are not considered to suffer from DoC anymore as they have emerged from the MCS (EMCS). This binary distinction is however subjective as they often remain severely handicapped both physically (e.g., with hemiplegia) and cognitively (e.g., with confusional state) and most of them will require intensive neurological rehabilitation and daily assistance for years, if not for life. As communication resumes, albeit rudimentary, the field of possibilities to test the patients’ cognitive functions widens tremendously. Using adapted versions of common neuropsychological tests, a comprehensive assessment of cognitive deficits can be made to detect common conditions among these patients such as aphasia, confusion, memory and attention impairments, dysmetria or spatial neglect. The post-traumatic confusional state is a common syndrome that can occur following the recovery of consciousness among TBI patients, and it has been recently defined with specific criteria. Additionally, researchers advocate the use of a more extensive and specific neuropsychological workup to warrant the EMCS, at least in the case of traumatic etiologies.

Locked-in syndrome

Preserved consciousness with quadriplegia and anarthria

The LIS does not formally belong to the class of DoC, but is a common differential diagnosis that must systematically be mentioned and excluded when assessing severely brain-injured patients with potential brainstem involvement. Already pictured in The Count of Monte Cristo by Alexandre Dumas in the early 19th century, this peculiar condition was given its name by Plum and Posner to define a state with quadriplegia and anarthria despite preserved consciousness. The classic presentation features a total paralysis of all limb and face muscles, with the exception of eye movements that can be used to communicate using a predefined code, an alphabetic grid or assistive technology. However, patients rarely display the full range of typical symptoms in clinical practice, and the term “partial locked-in syndrome” is sometimes employed for patients with residual motor or verbal function. The symptomatology derives from bilateral lesions to the motor efferent pathways in the brainstem, notably cortico-spinal and cortico-bulbar tracts. The majority of cases result from a bilateral vascular event in the posterior circulation, usually an ischemic stroke of the basilar artery due to thrombosis or embolism. The paramedian base of the pons is particularly vulnerable to infarction due to its poor supply by collateral arteries, in contrast with the tegmentum which is often spared. Pontine hemorrhage due to hypertension or vascular malformations have low survival rates but can also lead to LIS. Several other etiologies have been described to cause this condition, such as TBI, tumors, pontine myelinolysis or toxic causes, but they are often associated with partial locked-in presentations. Despite the preservation of cognitive functions in these patients, their management is a challenge as they can often be mistaken for UWS patients, and an efficient rehabilitation framework for LIS patients is lacking. Long-term overall prognosis is poor as functional recovery of motor function or speech are rarely achieved, however the common representation of hopelessness and total absence of progress is inaccurate. Indeed, a survey showed that a majority of chronic LIS patients partially recover movements and are able to use assisted technology to help them communicate in the long term, although the sample selection might have been biased by the necessity to communicate to answer the survey, leaving out the most severe fraction of this population. Contrary to popular beliefs, the self-reported quality of life among LIS patients is rather high and comparable to healthy individuals for those who can achieve and maintain communication, although some reports have shown the presence of a bimodal distribution with a minority of highly distressed patients.

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Diagnostic Tools

Simplified Evaluation of CONsciousness Disorders - Seconds

We here propose a novel behavioral diagnostic tool to assess the level of consciousness in patients with severe brain injury, the Simplified Evaluation of CONsciousness Disorders (SECONDs). This scale includes eight items: observation, command-following, communication (intentional or functional - conditional item), visual pursuit, visual fixation, localization to pain (conditional item), oriented behaviors, and arousal.

Administration and scoring procedure

Items should be administered sequentially from A to H: observation (A), command-following (B, score 6), communication (C, conditional, scores 7 and 8), visual pursuit (D, score 4), visual fixation (E, score 3), localization to pain (F, conditional, score 2), oriented behaviors (G, score 5) and arousal (H, scores 1 and 0). This sequence does not follow the scores of the items ordinally. This order was designed to optimize the allocation of the patient's attentional capacities and reduce administration duration. Communication and localization to pain are conditional items and must be administered only under certain conditions (see corresponding sections). The final score corresponds to the score of the highest succeeded item and directly reflects the diagnosis. An additional index score ranging from 0 to 100 can be calculated to obtain a more accurate measure of the observed behaviors and allows following the evolution of the patient over time (see corresponding section). All scores and observations should be consigned in the provided scoring sheets.

At any time during the assessment, if no sustained eye-opening is observed or if the patients stops following commands for at least one minute, administer auditory (i.e., use patient's own name, clapping hands), tactile (i.e., CRS-R arousal facilitation protocol75), or noxious stimulation (i.e., pressure on fingernail bed) to arouse the patient. During the entire assessment, promote eye-opening before testing each item if needed. Observe the patient and report the presence of eye-opening, either spontaneously or in response to stimulation, as well as the presence of self-oriented behaviors or behaviors oriented toward the environment. See sections G and H for detailed scoring guidelines of oriented behaviors and arousal. If eye-opening is not possible, oculomotor command-following, visual pursuit, and visual fixation (see sections B, D, E) should be assessed by opening the patient's eyes manually.

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