Definitions of altered consciousness: Coma is a pathological state of unconsciousness in which the eyes remain closed; the patient cannot be aroused by the application of stimulation and there is an absence of sleep-wake cycles. Vegetative state (VS), sometimes referred to as wakeful unconsciousness, is manifested by the inability to purposefully interact with others or the environment but with intermittent eye opening and the presence of sleep-wake cycles. The minimally conscious state (MCS) is manifested by minimal but definitive evidence of self or environmental awareness.1 MCS is further classified into plus (+) and minus (-), with MCS+ indicating preservation of residual language function with the presence of command following, intelligible verbalization and/or intentional communication. MCS- includes behaviors such as automatic motor behaviors (e.g. scratching nose), localizing noxious stimuli, visual pursuit or fixation, and object manipulation but without evidence of preserved language function.2 Cognitive motor dissociation (CMD), also known as covert consciousness or “functional locked-in syndrome”, is manifested by consciousness in a patient whose exam suggests coma, VS or MCS-.3 Locked-in syndrome (LIS) is not a disorder of consciousness, but is often misdiagnosed as VS or MCS because of paralysis of all 4 limbs and most facial muscles.
Epidemiology including risk factors and primary prevention
The vast majority of individuals who sustain and survive traumatic brain injury (TBI) beyond the acute stage regain consciousness, although reported incidences of those remaining in VS and MCS for prolonged timed periods vary. The annual incidence of VS in the United States is approximately 4200, while that of MCS is unknown.4 In a cohort study of 17,470 TBI patients, 57% experienced initial loss of consciousness, with 12% having persistence of loss of consciousness after acute care; 98% of these patients regained consciousness by the end of subsequent inpatient rehabilitation.5
Coma is often the result of severe, diffuse, bilateral lesions of the cortex and/or underlying white matter, bilateral thalamic injury, or lesions of the paramedian tegmentum. Trauma induced VS is often associated with diffuse axonal injury and severe thalamic degeneration. Limited reports in cases of MCS suggest wide variation in underlying anatomic correlates. Nontraumatic causes of Disorders of Consciousness (DOC) often involve severe bilateral thalamic pathology and diffuse cortical damage.
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
The Coma Recovery Scale – Revised (CRS-R) is the most widely used tool to assess DOC regarding diagnosis and trajectory and is described in the supplemental assessment tools heading below. Coma is self-limiting post-TBI, typically lasting no more than 2 weeks in those who survive. Afterwards, people may emerge into the VS or MCS. Previously, the terms persistent and permanent VS were used to define phases of VS. However, after an analysis of long-term outcomes, it was found that emergence into a higher level of consciousness occurred after a prolonged period following trauma in a substantial minority of those in VS. Thus, the use of “persistent” and “permanent” VS should be abandoned. The term “chronic VS” should be used in cases of greater than 3 months in non-traumatic cases and greater than 12 months in traumatic cases.6 Emergence from MCS is signaled by interactive and accurate communication and/or use of functional object(s). Recent evidence reveals most people with TBI in a coma recover consciousness in the short term and almost half regain function independence.5 When discussing prognosis with caregivers of patients with a DOC during the first 28 days post injury, clinicians should avoid statements that suggest these patients have a universally poor prognosis.6
Essentials of Assessment
Serial bedside evaluations are essential to elicit and distinguish between reflexive and voluntary responses to various forms of stimulation that differentiate VS from MCS. Clinicians should attempt to increase arousal before performing evaluations to assess level of consciousness any time impaired arousal is observed or suspected. Conditions that may confound the diagnosis of DOC should be identified and treated prior to establishing a final diagnosis.6 The CRS-R guides assessments, which includes but is not limited to determining the ability to use objects functionally. Infrequent responses to complex commands are typically adequate to determine the presence of consciousness, whereas consistent responses to simple commands are required for the same. Misdiagnosis of DOC is consistently reported to be approximately 40%.7
Presently, no laboratory studies, including imaging, definitively diagnose DOC, and are note used for this purpose.7 There is limited evidence supporting the use of specific technologies to assist with prognosis (see early predictions of outcomes).
Clinicians can consider MRI six to eight weeks post injury for those in the VS to assess for injury to the corpus callosum, dorsolateral upper brainstem, or corona radiata, which is associated with remaining in the VS at 12 months following TBI. Similarly, a SPECT scan one to two months post injury can assist in 12-month prognostication of recovery of consciousness and degree of disability/recovery for patients in traumatic VS.6 Some evidence suggests functional magnetic resonance imaging (fMRI) may be useful to detect consciousness in some subjects who clinically appear to be in VS.8 Positron emission tomography (PET) and magnetoencephalography (MEG) may offer similar utility.
Supplemental assessment tools
The JFK Coma Recovery Scale Revised (CRS-R) is the most widely used and recommended assessment tool. It assists with differential diagnosis, prognosis, and treatment planning. It assesses 6 domains, including auditory, visual, motor, oromotor/verbal and communication functions in addition to arousal. Responses are arranged in a hierarchal format progressing from brain stem-mediated to cortical functions. Scores range from 0-23 with higher scores indicative of higher cortical function.
Early predictions of outcomes
Ability to follow commands prior to 28 days post-TBI is associated with greater functional independence at 1, 2, 5 and 10 years post injury. Improvement in functional independence is also achievable between 5 and 10 years post injury.9 There is moderate confidence suggesting functional MRI, P300, reactive EEG, presence of hydrocephalus and the CRS-R can prognosticate in adults. However, no tests have similar confidence to improve prognostic accuracy in children.7 Emergence from VS to MCS within 5 months of injury and traumatic etiology are independently associated with more favorable outcomes. Individuals in MCS who receive early rehabilitation (within the first 6 months after brain injury) are also more likely to have better outcomes. Severity and type of comorbidities are associated with outcomes. Ischemic or organic heart disease is a strong predictor for mortality while respiratory disease and arrhythmias without ischemic heart disease is a negative predictor of full recovery and functional improvements.10 Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion are associated with better functional outcomes.5
Limited assessment instruments and high diagnostic error rates complicate ethical and legal decisions regarding care planning, end of life decisions, issues pertaining to intentional trauma and criminal charges, participation in research, resource allocation, and benefits of partially improved function via new treatments versus increased personal awareness of disability causing despair.
Rehabilitation Management and Treatments
Available or current treatment guidelines
Recent updates to management guidelines and minimum competency recommendations for programs providing services to people with DOC are available.7,11 These include using a multidisciplinary team of brain injury professionals. A systematic approach to health maintenance and prevention of complications related to immobility, including skin care, pulmonary hygiene, limb range of motion, and management of spasticity, pain and bowel/bladder needs are important components of DOC care. Environmental factors that may affect behavior require ongoing assessment. Validated measures to assess rate and trajectory of recovery should be used.11 100-200 mg of amantadine hydrochloride twice daily should be prescribed early post-TBI to enhance the rate of recovery of those receiving inpatient rehabilitation while in the VS or MCS.12 Multi-modal sensory stimulation provided via either naturally occurring environmental exposure or through a structured program is frequently used, although has very limited proven efficacy. Neuromodulation, either through the provision of pharmacological stimulants other than amantadine (e.g., cholinergic, dopaminergic, and/or serotonergic agonists) or the minimization of CNS depressants (e.g., anticonvulsants, benzodiazepines) may be helpful, but remains unproven and protocols are not standardized.11
Patient & family education
Family education regarding prognosis, limited data pertaining to treatment efficacy, long-term planning, and long term care are essential components of DOC care especially in cases of poor prognosis.
Cutting Edge/ Emerging and Unique Concepts and Practice
A meta-analysis of the use of transcranial direct current stimulation (tDCS) in people with disorders of consciousness indicates that stimulation over the dorsolateral prefrontal cortex is an effective treatment for enhancing behavioral performance, noting those in the MCS showed the greatest response.13 Limited evidence suggests deep brain stimulation (DBS) to specific thalamic regions with projections to the cortex may enhance cognitive and physical function. Other potentially efficacious, although unproven, treatments include median nerve stimulation, spinal cord stimulation, intrathecal baclofen and extradural cortical stimulation.
Gaps in the Evidence- Based Knowledge
Treatment effectiveness of many modalities and definitive assessment tools for accurate diagnosis remain elusive.
- Giacino JT, Fins JJ, Laureys S, Schiff ND. Disorders of consciousness after acquired brain injury: the state of the science. Nat Rev Neurol. 2014;10(2):99-114. doi: 10.1038/nrneurol.2013.279. Epub 2014 Jan 28.
- Thibaut A, Bodien YG, Laurey S, Giacino JT. Minimally conscious state “plus”: diagnostic criteria and relation to functional recovery. J Neurol (2019) https://doi-org.ezproxy.med.nyu.edu/10.1007/s00415-019-09628-y.
- Edlow BL, Claassen J, Schiff ND, Greer DM. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat Rev Neurol. 2021 Mar;17(3):135-156. doi: 10.1038/s41582-020-00428-x. Epub 2020 Dec 14. PMID: 33318675; PMCID: PMC7734616.
- Jennett, B. The vegetative state. J Neurol Neurosurg Psychiatry 2002;73:355-357.
- Kowalski RG, Hammond FM, Weintraub AH, Nakase-Richardson R, Zafonte RD, Whyte J, Giacino JT. Recovery of Consciousness and Functional Outcome in Moderate and Severe Traumatic Brain Injury. JAMA Neurol. 2021 May 1;78(5):548-557. doi: 10.1001/jamaneurol.2021.0084. PMID: 33646273; PMCID: PMC7922241.
- Giacino JT, Katz DI, Schiff ND, et al. Practice Guideline Update Recommendations Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Arch Phys Med Rehabil. 2018;99(9):1699-1709. doi: 10.1016/j.apmr.2018.07.001. Epub 2018 Aug 8.
- Giacino JT, Katz DI, Schiff ND, et al. Comprehensive Systematic Review Update Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Arch Phys Med Rehabil. 2018;99(9):1710-1719. doi: 10.1016/j.apmr.2018.07.002. Epub 2018 Aug 8.
- Monti MM, Vanhaudenhuyse A, Coleman MR, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med. 2010;362(7):579-589.
- Hammond FM, Giacino JT, Nakase Richardson R, et al. Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten Years Post-Injury. J Neurotrauma 2019;36(7):1136-1146. doi: 10.1089/neu.2018.5954. Epub 2018 Oct 19.
- Pistoia F, Sacco S, Franceschini M, et al. Comorbidities: a key issue in patients with disorders of consciousness. J Neurotrauma 2015;32(10):682-688.
- Giacino JT, Whyte J, Nakase-Richardson R, et al. Minimum Competency Recommendations for Programs that Provide Rehabilitation Services for Persons with Disorders of Consciousness: A Position Statement of the American Congress of Rehabilitation Medicine and the National Institute on Disability, Independent Living and Rehabilitation Research Traumatic Brain Injury Model Systems. Arch Phys Med Rehabil. 2020 Feb 19. pii: S0003-9993(20)30093-9. doi: 10.1016/j.apmr.2020.01.013. [Epub ahead of print])
- Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366(9):819-286.
- Xu Z, Zheng R, Xia T, Qi Z, Zang D, Wang Z, Wu X. Behavioral effects in disorders of consciousness following transcranial direct current stimulation: A systematic review and individual patient data meta-analysis of randomized clinical trials. Front Neurol. 2022 Sep 29;13:940361. doi: 10.3389/fneur.2022.940361. PMID: 36247787; PMCID: PMC9558708.
Original Version of Topic
Steven Flanagan, MD. Disorders of Consciousness. 11/10/2011
Previous Revision(s) of the Topic
Steven Flanagan, MD. Disorders of Consciousness. 9/17/2015
Steven Flanagan, MD, William Tsai, MD. Disorders of Consciousness. 7/22/2020
Steven Flanagan, MD
Nothing to disclose
Jing Lin, MD
Nothing to disclose