A vegetative state is absence of responsiveness and awareness due to overwhelming dysfunction of the cerebral hemispheres, with sufficient sparing of the diencephalon and brain stem to preserve autonomic and motor reflexes and sleep-wake cycles. Patients may have complex reflexes, including eye movements, yawning, and involuntary movements to noxious stimuli, but show no awareness of self or environment. A minimally conscious state, unlike a vegetative state, is characterized by some evidence of awareness of self and/or the environment, and patients tend to improve. Diagnosis is clinical. Treatment is mainly supportive. Prognosis for patients with persistent deficits is typically bleak.
The vegetative state (sometimes called unresponsive wakefulness syndrome) is a chronic condition that preserves the ability to maintain blood pressure (BP), respiration, and cardiac function, but not cognitive function. Hypothalamic and medullary brain stem functions remain intact to support cardiorespiratory and autonomic functions and are sufficient for survival if medical and nursing care is adequate. The cortex is severely damaged (eliminating cognitive function), but the reticular activating system (RAS) remains functional (making wakefulness possible). Midbrain or pontine reflexes may or may not be present. Patients usually have no awareness of self and interact with the environment only via reflexes. Seizure activity may be present but not be clinically evident.
Traditionally, a vegetative state that lasts > 1 month is considered to be a persistent vegetative state. (However, other durations have been proposed, sometimes depending on the cause.) (1) A diagnosis of persistent vegetative state does not imply permanent disability, however, because in very rare cases (eg, after traumatic brain injury), patients can improve, reaching a minimally conscious state or a higher level of consciousness.
The most common causes of a vegetative state and minimally conscious state are
Diffuse cerebral hypoxia
However, any disorder that results in brain damage can cause a vegetative state. Typically, a vegetative state occurs because the function of the brain stem and diencephalon resumes after coma, but cortical function does not.
In the minimally conscious state, unlike the vegetative state, there is evidence that patients are aware of themselves and/or their environment. Patients also tend to improve (ie, gradually become more conscious), but improvement is limited. This state may be the first indication of brain damage or may follow a vegetative state as people recover some function. Patients can transition between the vegetative state and minimally conscious state, sometimes for years after the original brain damage.
General reference
1. Quiñones-Ossa GA, Durango-Espinosa YA, Janjua T, et al: Persistent vegetative state: an overview. Egypt J Neurosurg 36:9, 2021. doi: 10.1186/s41984-021-00111-3
Symptoms and Signs
Vegetative state
Patients in a vegetative state show no evidence of awareness of self or environment and cannot interact with other people. Purposeful responses to external stimuli are absent, as are language comprehension and expression.
The following are present in patients in a vegetative state:
Signs of an intact reticular formation (eg, eye opening) and an intact brain stem (eg, reactive pupils, oculocephalic reflex)
Sleep-wake cycles, not necessarily reflecting a specific circadian rhythm nor associated with the environment
More complex brain stem reflexes, including yawning, chewing, swallowing, and, uncommonly, guttural vocalizations
Sometimes arousal and startle reflexes (eg, loud sounds or blinking with bright lights may elicit eye opening)
Sometimes watering and tearing of the eyes
Sometimes the appearance of a smile or frown
Spontaneous roving eye movements—usually slow, of constant velocity, and without saccadic jerks
The spontaneous roving eye movements may be misinterpreted as volitional tracking and can be misinterpreted by family members as evidence of awareness.
Patients cannot react to visual threat and cannot follow commands. The limbs may move, but the only purposeful motor responses that occur are primitive (eg, grasping an object that contacts the hand). Pain usually elicits a motor response (typically decorticate or decerebrate posturing) but no purposeful avoidance. Patients have fecal and urinary incontinence. Cranial nerve and spinal reflexes are typically preserved.
Rarely, brain activity, detected by functional MRI or electroencephalography (EEG), indicates a response to questions and commands even though there is no behavioral response (covert consciousness) (1, 2). The extent of patients' actual awareness is not yet known. In most patients who have such brain activity, the vegetative state resulted from traumatic brain injury, not hypoxic encephalopathy.
Minimally conscious state
Fragments of meaningful interaction with the environment are preserved. Patients in a minimally conscious state may do the following:
Establish eye contact
Purposefully grasp at objects
Respond to commands in a stereotypic manner
Answer with the same word
Symptoms and signs references
1. Owen AM, Coleman MR, Boly M, et al: Detecting awareness in the vegetative state. Science 313 (5792):1402, 2006. doi: 10.1126/science.1130197
2. Monti MM, Rosenberg M, Finoia P, Kamau E, Pickard JD, Owen AM: Thalamo-frontal connectivity mediates top-down cognitive functions in disorders of consciousness. Neurology 84(2):167–173, 2015. doi:10.1212/WNL.0000000000001123
Diagnosis
Clinical criteria after sufficient observation
Neuroimaging
A vegetative state is suggested by characteristic findings (eg, no purposeful activity or comprehension) plus signs of an intact reticular formation. Diagnosis is based on clinical criteria. However, neuroimaging is indicated to rule out treatable disorders.
The vegetative state must be distinguished from the minimally conscious state. Both states can be permanent or temporary, and the physical examination may not reliably distinguish one from the other. Sufficient observation is needed. If observation is too brief, evidence of awareness may be overlooked. Some patients with severe Parkinson disease are misdiagnosed as being in a vegetative state.
CT or MRI can differentiate an ischemic infarct, an intracerebral hemorrhage, and a mass lesion involving the cortex or the brain stem. Magnetic resonance angiography can be used to visualize the cerebral vasculature after exclusion of a cerebral hemorrhage. Diffusion-weighted MRI is becoming the preferred imaging modality for following ongoing ischemic changes in the brain.
Positron emission tomography (PET), functional MRI, and single-photon emission computed tomography (SPECT) can be used to assess cerebral function (rather than brain anatomy). If the diagnosis of persistent vegetative state is in doubt, PET, SPECT, or functional MRI should be done. In some cases, these tests can show whether parts of the brain, such as the cortex, are still functioning even if it is not evident during clinical examination.
EEG is useful in assessing cortical dysfunction and identifying occult seizure activity.
Treatment
Supportive care
Supportive care is the mainstay of treatment for patients in a vegetative state or minimally conscious state; it should include the following:
Preventing systemic complications due to immobilization (eg, pneumonia, urinary tract infection, thromboembolic disease)
Providing good nutrition
Providing physical therapy to prevent limb contractures
Vegetative state has no specific treatment. Decisions about life-sustaining care should involve social services, the hospital ethics committee, and family members. Maintaining patients, especially those without advance directives to guide decisions about terminating treatment, in a prolonged vegetative state raises ethical and other (eg, resource utilization) questions.
123) can lead to improvement in neurologic responsiveness for as long as the medication is continued.
A growing number of studies are evaluating the effects of providing music interventions during disorders of consciousness (4). Some studies show that music therapy may lead to positive behavioral effects and return to normal physiologic responses. Results should be interpreted with caution because research in this area has thus far been limited.
Treatment references
1. Du B, Shan A, Zhang Y, et al: Zolpidem arouses patients in vegetative state after brain injury: Quantitative evaluation and indications. Am J Med Sci 347 (3):178–182, 2014. doi: 10.1097/MAJ.0b013e318287c79c
2. Fridman EA, Krimchansky BZ, Bonetto M, et al: Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury. Brain Inj 24 (4):636–641, 2010. doi: 10.3109/02699051003610433
3. Gao Y, Zhang Y, Li Z, Ma L, Yang JMedicine (Baltimore). 2020;99(33):e21822. doi:10.1097/MD.0000000000021822
4. Li X, Li C, Hu N, Wang T: Music interventions for disorders of consciousness: A systematic review and meta-analysis. J Neurosci Nurs 52(4): 146–151, 2020. doi: 10.1097/JNN.0000000000000511
Prognosis
Vegetative state
Prognosis varies somewhat by cause and duration of the vegetative state. Prognosis may be better if the cause is a reversible metabolic condition (eg, toxic encephalopathy) than if the cause is neuronal death due to extensive hypoxia and ischemia or another condition. Also, younger patients may recover more motor function than older patients but not more cognition, behavior, or speech.
Recovery from a vegetative state depends on the cause. It is unlikely after 1 month if brain damage is nontraumatic and after 12 months if brain damage is traumatic.
Even if some recovery occurs after these intervals, most patients are severely disabled. Rarely, improvement occurs late; after 3 to 5 years, few patients (eg, about 3 to 5%) (1) recover the ability to communicate and comprehend, but even fewer can live independently; no patients regain normal function.
If a vegetative state persists, most patients die within 6 months of the original brain damage. The cause is usually pulmonary infection, urinary tract infection, or multiple organ failure, or death may be sudden and of unknown cause. For most of the rest, life expectancy is about 2 to 5 years (1). A few patients live for decades.
Minimally conscious state
Most patients tend to recover consciousness but to a limited extent depending on how long the minimally conscious state has lasted. The longer it has lasted, the less chance of patients recovering higher cortical function. Prognosis may be better if the cause is traumatic brain injury.
Rarely, patients regain clear but limited awareness after years of coma, called awakenings by the news media.
Prognosis reference
1. Baricich A, de Sire A, Antoniono E, et al. Recovery from vegetative state of patients with a severe brain injury: a 4-year real-practice prospective cohort study. Funct Neurol. 2017;32(3):131-136. doi:10.11138/fneur/2017.32.3.131
Key Points
Vegetative state is typically characterized by absence of responsiveness and awareness due to overwhelming dysfunction of the cerebral hemispheres, intact brain stem function, and sometimes the simulation of awareness despite its absence.
Minimally conscious state differs from vegetative state in that patients have some interaction with the environment and tend to improve over time.
Diagnosis requires exclusion of other disorders and often prolonged observation, particularly to differentiate vegetative state, minimally conscious state, and Parkinson disease.
Prognosis tends to be poor, particularly for patients in a vegetative state.
Treatment is mainly supportive.
