Author(s): Steven Flanagan, MD, Jessie Chan, MD
Originally published: November 10, 2011 Last updated: August 10, 2026
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Disease/Disorder

Definition

Definitions of altered consciousness: Coma is a pathological state of unconsciousness characterized by lack of arousal and awareness; the patient cannot be aroused by the application of stimulation and there is an absence of eye opening or sleep-wake cycles on electroencephalography (EEG). It differs from brain death, also known as death by neurologic criteria in that the latter is a permanent loss of brain function as whole, including the brain stem that meets specific criteria.  The unresponsive wakefulness state (UWS) is a dissociative state of wakefulness without awareness and is manifested by the inability to purposefully interact with others or the environment.1 In UWS there is preserved behavioral sleep as characterized by intermittent eye opening, however an absence of sleep-wake cycles on EEG.2 The minimally conscious state (MCS) is manifested by inconsistent but reproducible evidence of self or environmental awareness and command following.1 MCS is further classified into plus (+) and minus (-), with MCS+ indicating preservation of residual language function with the presence of 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.3 Cognitive motor dissociation (CMD) is a phenomenon in which patients show appropriate brain activation to command on functional magnetic resonance imaging (fMRI) or EEG but remain behaviorally unresponsive.4 Locked-in syndrome (LIS) is not a disorder of consciousness, but is often misdiagnosed as UWS or MCS because of paralysis of all 4 limbs and most facial muscles.1

Etiology

  • Trauma
  • Ischemia
  • Hypoxia
  • Toxic/metabolic

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 UWS and MCS for prolonged timed periods vary. The annual incidence of UWS in the United States is approximately 4200 with prevalence ranging from 5000 to 42000. Prevalence of MCS is estimated to range between 112000-280000. The rate of misdiagnosis for disorders of consciousness (DOC) is often cited as around 40%, however epidemiological data is difficult to track due to lack of a diagnostic code in the 10th revision of the International Classification of Diseases (ICD-10) system.5 ICD-11, which has yet to be adopted in the United States, now includes codes for UWC, MCS-, and MCS+ which should promote future epidemiological work.6,7 A crowdsourced survey estimated the annual incidence of coma in the United States as 258 per 100000 population and prevalence of 31 cases per 100000.7

Patho-anatomy/physiology

Consciousness encompasses both arousal and awareness.  The ascending reticular activating system, a network of nuclei and their projections with multiple neurotransmitters originating in the brainstem, is the essential structure responsible for arousal.  It interfaces with the thalamus, hypothalamus and forebrain through multiple connections, including but not limited to the ventral tegmental area to maintain arousal. Awareness is a cortical function, involving the dorsolateral prefrontal cortex, posterior parietal cortex and components of the default mode network.  Collectively, these brainstem and cortical regions work in concert to maintain consciousness. Coma is often the result of broad depression of excitatory synaptic activity throughout the cerebral cortex. UWS, with preserved wakefulness but impaired awareness, suggests preserved brainstem function with cortical dysfunction. Presence of awareness and limited but present cognitive functioning in MCS points to preservation of corticothalamic function.1

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Coma is self-limiting post-TBI, typically lasting no more than 1-3 weeks in those who survive. Afterwards, people may emerge into the UWS or MCS. The term “chronic UWS” should be used in cases of greater than 3 months in non-traumatic cases and greater than 12 months in traumatic cases.5 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 functional independence.8 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.5

Essentials of Assessment

History

See etiology.

Physical examination

Serial bedside evaluations are essential to elicit and distinguish between reflexive and voluntary responses to various forms of stimulation that differentiate UWS 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 and medications that may confound the diagnosis of DOC should be identified and addressed prior to establishing a final diagnosis,5which requires a general medical and neurological examination and pertinent history. 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. The CRS-R includes testing for visual pursuit and fixation as well as automatic motor responses, which are important for assessment of DOC and are not captured in the Glasgow Coma Scale (GCS), but requires approximately 30 minutes to administer, thus is not practical for bedside serial assessment. Adaptations such as the CRS-R For Accelerated Standardized Testing (CRSR-FAST) and the Simplified Evaluation of CONsciousness Disorders (SECONDs) can be used for rapid assessment of level of consciousness and captures more detail than the GCS. Serial assessments are critical in order to have multiple data points to make a diagnosis of DOC which often presents with fluctuations in awareness and wakefulness.7   The examiner needs to also consider medical conditions such as possible hearing or vision loss, aphasia and paralysis that may confound the assessment of consciousness.

Laboratory studies

Presently, no laboratory studies, including imaging, definitively diagnose DOC, and are not used for this purpose. There is no established systematic approach for assessing patients for DOC, especially in the acute hospital setting.7

Imaging

Clinicians can consider MRI six to eight weeks post injury for those in the UWS to assess for injury to the corpus callosum, dorsolateral upper brainstem, or corona radiata, which is associated with remaining in the UWS 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 UWS. Some evidence suggests fMRI may be useful to detect consciousness in some subjects who clinically appear to be in UWS. Positron emission tomography (PET) and magnetoencephalography (MEG) may offer similar utility.9

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 hierarchical format progressing from brainstem-mediated to cortical functions.  Scores range from 0-23 with higher scores indicative of higher cortical function.7,10

Early predictions of outcomes

Etiology of DOC can be helpful in providing prognosis; traumatic brain injuries are associated with more favorable outcomes as compared to non-traumatic causes such as hypoxic-ischemic brain injury after cardiac arrest.11

The American Academy of Neurology recommends deferring a poor prognosis for recovery for at least 28 days from time of injury. Studies have found that emergence from UWS is most likely in the first 3 months for non-traumatic etiologies and in the first 12 months for traumatic etiologies. Once patients enter the chronic phase of UWS, emergence remains possible however severe and permanent disability is expected.5

Accurate diagnosis of DOC is important for prognosis, as level of consciousness can be a predictor of outcome. Amongst patients with DOC for greater than 28 days, those in MCS within 5 months post-injury are more likely to have greater functional recovery compared to patients who remain in UWS.5 CMD is often diagnosed using EEG or fMRI, and is associated with improved functional recovery at 12 months post-injury compared to those in MCS or UWS.12 fMRI, EEG, P300 component on long-latency event-related potentials, brain computer interface, PET, and transcranial magnetic stimulation (TMS) have been areas of significant research and interest for diagnosing DOC.11,13 Although studies have demonstrated evidence for these modalities as part of a multi-modal approach to diagnosis, further research is required to interpret the results and standardize their application.11

Younger age, traumatic etiology, and subdural hematoma are associated with better functional outcomes.12 Ability to follow commands within 28 days of traumatic brain injury is associated with better long-term functional outcomes compared to those who do not.14 Advanced age, premorbid medical conditions or disability, polytrauma, history of brain injury, and lower level of education have been correlated with poorer function outcomes in patients with DOC.11

Professional issues

Limited assessment instruments and high diagnostic error rates complicate ethical and legal decisions regarding care planning (including withdrawal of care), 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.11 These include using a multidisciplinary team of brain injury professionals, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, and neuropsychologists. 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, clinical, and iatrogenic factors that may affect behavior require ongoing assessment.15 Validated measures to assess rate and trajectory of recovery should be used.7100-200 mg of amantadine hydrochloride twice daily can be prescribed early post-TBI to enhance the rate of functional recovery of those receiving inpatient rehabilitation while in the UWS or MCS.16 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 have limited strong evidence for efficacy and protocols are not standardized.15 Zoldipem has been studied for its paradoxical effect in patients with DOC and promoted wakefulness in a limited number (4.8%) of study participants.17 A study found that methylphenidate may improve connectivity between the ventral tegmental area (VTA) and the precuneus/posterior cingulate cortex which correlates with consciousness level.18

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) and TMS 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. Median nerve stimulation (MNS) utilizes the connection between the median nerve spinal segment and the ascending reticular activating system to promote consciousness.  A multicenter study demonstrated that MNS is more effective than placebo. Vagus nerve stimulation (VNS) directly targets brainstem activity and there is some evidence for advancement in level of consciousness with transcutaneous VNS, although it appeared to be effective for MCS patients, not for UWS patients. 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 spinal cord stimulation and extradural cortical stimulation.19

Gaps in the Evidence-Based Knowledge

In general, results of neuromodulation studies as a treatment to enhance recovery have been mixed and confounded by natural recovery and pharmacological interventions, thus require additional investigations.20 As previously noted, there are no laboratory studies, including imaging that definitively diagnose DOC.  Similarly, CMD is a relatively new concept that lacks a widely accepted definition and standard means of diagnosis, noting a computational analysis of multimodal assessments has been proposed.21

References

  1. Weitzel L, Bavishi S. Disorders of Consciousness. Phys Med Rehabil Clin N Am. 2024;35(3):493-506. doi:10.1016/j.pmr.2024.02.003
  2. Landsness E, Bruno MA, Noirhomme Q, et al. Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state. Brain. 2011;134(8):2222-2232. doi:10.1093/brain/awr152
  3. Schnakers C, Majerus S. Behavioral Assessment and Diagnosis of Disorders of Consciousness. In: Schnakers C, Laureys S, eds. Coma and Disorders of Consciousness. Springer International Publishing; 2018:1-16. doi:10.1007/978-3-319-55964-3_1
  4. Bodien YG, Allanson J, Cardone P, et al. Cognitive Motor Dissociation in Disorders of Consciousness. N Engl J Med. 2024;391(7):598-608. doi:10.1056/NEJMoa2400645
  5. 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. Neurology. 2018;91(10):461-470. doi:10.1212/WNL.0000000000005928
  6. International Classification of Diseases 11th Revision. International Classification of Diseases 11th Revision. January 1, 2022. Accessed February 15, 2026. https://www.who.int/standards/classifications/classification-of-diseases
  7. Bodien YG, Busl KM, Chang CWJ, et al. Disorders of consciousness diagnosis, interventions, and prognostication for the intensivist: Report of the 2025 ISICEM roundtable. Intensive Care Med. 2026;52(1):42-62. doi:10.1007/s00134-025-08224-1
  8. Kowalski RG, Hammond FM, Weintraub AH, et al. Recovery of Consciousness and Functional Outcome in Moderate and Severe Traumatic Brain Injury. JAMA Neurol. 2021;78(5):548-557. doi:10.1001/jamaneurol.2021.0084
  9. Zasler ND, Arciniegas DB, Katz DI, et al., eds. Structural Neuroimaging. In: Brain Injury Medicine: Principles and Practice. 3rd ed. Springer Publishing Company; 2021:192-214. doi:10.1891/9780826143051
  10. Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: Measurement characteristics and diagnostic utility11No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Arch Phys Med Rehabil. 2004;85(12):2020-2029. doi:10.1016/j.apmr.2004.02.033
  11. Russell ME, Hammond FM, Murtaugh B. Prognosis and enhancement of recovery in disorders of consciousness. Schnakers C, Zasler ND, eds. NeuroRehabilitation. 2024;54(1):43-59. doi:10.3233/NRE-230148
  12. Egbebike J, Shen Q, Doyle K, et al. Cognitive-motor dissociation and time to functional recovery in patients with acute brain injury in the USA: a prospective observational cohort study. Lancet Neurol. 2022;21(8):704-713. doi:10.1016/S1474-4422(22)00212-5
  13. Estraneo A, Fiorenza S, Magliacano A, et al. Multicenter prospective study on predictors of short-term outcome in disorders of consciousness. Neurology. 2020;95(11):e1488-e1499. doi:10.1212/WNL.0000000000010254
  14. 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
  15. 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;101(6):1072-1089. doi:10.1016/j.apmr.2020.01.013
  16. 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):819-826. doi:10.1056/NEJMoa1102609
  17. Whyte J, Rajan R, Rosenbaum A, et al. Zolpidem and Restoration of Consciousness. Am J Phys Med Rehabil. 2014;93(2):101-113. doi:10.1097/PHM.0000000000000069
  18. Spindler LRB, Luppi AI, Adapa RM, et al. Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation. Proc Natl Acad Sci. 2021;118(30):e2026289118. doi:10.1073/pnas.2026289118
  19. He Q, Zhu S, Chai X, Cao T, Wang N, Yang Y. Advances in understanding and treating disorders of consciousness caused by brainstem injury. Chin Neurosurg J. 2025;11(1):25. doi:10.1186/s41016-025-00411-9
  20. Dutta RR, Abdolmanafi S, Rabizadeh A, Baghbaninogourani R, Mansooridara S, Lopez A, Akbari Y, Paff M. Neuromodulation and Disorders of Consciousness: Systematic Review and Pathophysiology. Neuromodulation. 2025 Apr;28(3):380-400.
  21. Vitturi BK. Multimodal assessment of minimally conscious state and cognitive motor dissociation in neurocritical care: A critical review. Rev Neurol (Paris). 2026 Jun 11:S0035-3787(26)00549-7.

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, Jing Lin, MD. Disorders of Consciousness. 5/18/2023

Author Disclosures 

Steven Flanagan, MD
Nothing to Disclose

Jessie Chan, MD
Nothing to Disclose