Low Level Neurological States Following Traumatic Brain Injury

By:  Nathan Zasler, MD

There is much that remains unknown about assessment and management of severe brain injury. This brief primer will attempt to examine a few critical topics as related to the terminology, evaluation and management in persons of low level neurological states (LLNSs) following acquired brain injury and in particular traumatic brain injury (TBI).


Coma is a state of unarousable, unresponsiveness. Neurobehaviorally, these patients typically present with eyes closed without evidence of opening either spontaneously or to external stimulation; do not follow commands; do not demonstrate goal directed/volitional behavior; do not verbalize or mouth words; and cannot sustain visual pursuit movements beyond a limited degree. One must exclude neurobehavioral signs and symptoms of "coma" secondary to pharmacologically treatment with agents such as paralytic or sedative drugs.

Vegetative state (VS) describes a condition in which the patient demonstrates arousal without concurrent awareness.Behaviorally, vegetative state patients have periods of eye opening, either spontaneously or following stimulation; may demonstrate responses to external stimulation including generalized responses to pain such as posturing, fast heart rate, sweating, as well as, motor responses such as a grasp reflex. 

Neither of the aforementioned types of behavior are felt to be representative of conscious awareness. Persons in VS also typically demonstrate vegetative functions such as sleep-wake cycles, more normal respiratory patterns and digestive system functions. Persons in VS also typically have "roving" eye movements without true visual tracking ability. The presence of the aforementioned sub-cortical responses should not be considered as diagnostic of VS as these findings may also be seen in minimally conscious patients (see below).

Patients in "persistent" and "permanent' vegetative state meet all the criteria neurobehaviorally that patients in vegetative state do. Generally, the modifier "persistent" is endorsed when VS has lasted for at least a month, however, there is so little agreement, in practice, regarding how this term is applied that it should probably be removed from the current neuromedical vocabulary. In general, a time frame of one year for traumatic and three months (some have advocated for a period of six months) for hypoxic-ischemic brain injury (HIBI) should be utilized for prognostic purposes relative to determining that emergence from vegetative state is statistically highly unlikely. Consensus opinion has dictated that after these time frames, it is appropriate to use the phrase "permanent vegetative state".

The word "permanent" in permanent vegetative state is a relative misnomer as there is no way to predict with 100% accuracy whether someone will emerge into a state of consciousness from an otherwise vegetative state. Additionally, clinicians should only determine prognosis for a patient who is vegetative at one year following trauma or three (and possibly up to 6) months following hypoxic-ischemic injury if there has been an adequate period of extended patient observation and sufficient neuromedical assessment to rule-out conditions potentially adversely affecting ongoing neurorecovery and/or neurobehavioral assessment. Many have advocated for dispensing with the term "vegetative state" due to the concern that it is both potentially pejorative and misunderstood alternative phraseologies such as post-coma-unawareness (PCU), among others, have been suggested and continue to be debated.

Patients who are in a minimally conscious state (MCS) are no longer in coma or VS but demonstrate low level neurobehavioral responses consistent with severe neurologic impairment and disability. Patients who are in MCS are able to demonstrate, albeit intermittently and possibly incompletely, some level of awareness to environmental stimulation consistent with the presence of cognitive function. The examining clinician must take into consideration both the frequency and the context of the behavioral response in order to interpret the meaningfulness and/or purposefulness of a given behavior. All patients in MCS produce, by definition, inconsistent responses to their environment that do not reach threshold for reliable and/or consistent communication.

Akinetic mutism (AM) is a neurobehavioral condition marked by severe disturbances in behavioral drive. In actuality, AM is a neurobehavioral subset of the MCS sub-group. Generally, a minimal degree of movement (kinesis) and speech is elicitable. As opposed to most other low level neurobehavioral disorders, akinetic mutism is associated with damage to dopaminergic pathways including the mesoceruleal, diencephalospinal, and/or mesocorticolimbic. Patients with frontal AM tend to be more vigilant than those with midbrain AM and may even demonstrate episodic agitation. Patients with AM typically demonstrate: eye opening with visual tracking; little to no spontaneous speech; and infrequent as well as minimal command following.

Locked-in syndrome (LIS) is a relatively rare albeit important neurobehavioral condition associated with lesions of the ventral pons (e.g. front part of the brainstem), more commonly associated with cerebrovascular disease (i.e. stroke) than TBI. Clinically, patients with LIS present with anarthria (inability to speak) and tetraplegia (paralysis of all limbs) in the "complete form" of the condition. Generally, such individuals will have intact cognitive function and arousal. Vertical eye movements and blinking are typically the only preserved motor abilities. There is typically also significant lower cranial nerve and sleep wake cycle dysfunction.


There is no way to clinically assess "internal awareness" at the bedside in a patient otherwise unable to motorically express such awareness relative to any external stimuli. Thus, it is possible that some patients who are indeed conscious at some level are labeled incorrectly as being in a vegetative state. Although sophisticated clinicians will be less likely to misdiagnose patients who are in MCS as being vegetative, misdiagnosis of VS in the presence of exam findings consistent with conscious behaviors remains, unfortunately, fairly common based on available literature. With as much confusion as there still is regarding such basic things as how to perform a bedside assessment of a patient in a LLNS it is no surprise that misdiagnosis occurs with some frequency.

Practitioners should also understand that there is no consensus opinion as of yet on whether neurodiagnostic or laboratory testing may diagnose VS per se. What is agreed to is that the diagnosis, at present, is best made by serial bedside neurobehavioral assessment. Thorough assessment is vital for determination of an accurate neurological diagnosis. One needs to ascertain that the patient is in good general health and that there are no issues with intercurrent infection that may mask the individual's true neurological status. Attempts should be made to assure that no sedating medications or abnormal metabolic states are negatively impacting on arousal level.

The patient/examinee should be assessed in bed for determination of full integumentary status and limb range of motion, among other important physical examination points. Additionally, and as feasible, it is preferable to also exam the person in a supported seating position to optimize arousal. Efforts should be made, particularly when, in the context of most forensic assessments, there may only be one exam, to do the assessment at a time of day when the person is normally most arousable. Over stimulation and/or an environment with distractions should be avoided to optimize examinee attentional capabilities. As related to the physical examination of the low level neurological patient/examinee, it is important to conduct a thorough general exam, and one not just germane to the neurological level of function of the individual in question. Specifically, appropriate evaluation of the examinee¹s general status including vital signs and multisystem assessment is paramount to providing a comprehensive understanding of the individual risk factors and/or complications associated with their low-level neurological state. Probably, two of the most important systems are the integument and musculoskeletal systems particularly as related to the potential negative repercussions of relative immobility. Neurological examination should include cranial nerve assessment 1-12, deep tendon reflexes including pathologic reflexes, sensory examination (including visual fields, audition and nociceptive/tactile responsiveness), cerebellar assessment and motor function testing, among other areas assessed. The mental status assessment of an individual in a low level neurological state relies on an in-depth, bedside, neurobehavioral assessment with focus on evidence of responses consistent with awareness versus lack thereof, best accomplished by fastidious attention to nuances of neurobehavioral assessment, as well as, use of validated assessment tools such as the Coma Recovery Scale ­ Revised.


Unfortunately, the media often inaccurately reports information regarding late recoveries following brain injury as apparent "miracles". All too often inadequate information is provided regarding pre-recovery neuromedical status, findings and treatment, and/or medications at time of recovery or changes therein. In many of these cases, there is sub-optimal follow-up to know what "happens" with these individuals. These types of cases are critical for practitioners to convey to fellow clinicians and should be considered "reportable".


There have been recent developments that further expand our understanding regarding brain function in patients in LLNSs, particularly as related to functional brain imaging studies. Recent work suggests that there may be wide variations in brain metabolism in VS and that some cerebral regions can actually retain partial function. Other research has demonstrated that painful stimulation can produce increased neuronal activity in certain parts of the cortex in patients in VS, even when resting brain metabolism was severely impaired; yet, this activation was felt to occur in seeming isolation and dissociation from higher-order associative areas of the cortex thought to be necessary for conscious perception.

Further functional imaging work using positron emission tomography (PET) work has demonstrated that recovery of consciousness is paralleled by restoration of functional connections between the deeper, older sections of the brain and the newer "higher" cortical centers of the brain. These studies provide further data that question long standing neurological dogma regarding the accuracy of the bedside assessment for VS diagnosis.

Such work should beg the question of how much we truly understand about VS and what the specificity and sensitivity is of our traditional bedside neurobehavioral assessment methods for defining conscious awareness in patients who may otherwise appear vegetative. Additionally, there is now limited functional imaging data to show that some patients in VS may actually show fragments of behavior that are not tied to conscious awareness yet clinically appear to suggest such behavior.


Prognostic variables that are commonly used to predict neurologic and functional outcome have been categorized into six broad categories based on: demographic variables, injury severity indices, neurological signs, neuroimaging studies, neuromedical markers and psychosocial ratings. Of the demographic factors, the relation between age and outcome has received the most attention.

Generally very young (less than 2 years of age) or very old (greater than 60 years of age) have worse outcomes, particularly relative to chance for survival. Research has demonstrated that severity indices hold the highest level of predictability when utilized within the first 2 weeks post-injury. Some of the factors that may correlate with poorer outcome and higher levels of acute mortality, include, Glasgow Coma Scale (GCS) score of 5 or less, prolonged post-traumatic amnesia, abnormal brainstem findings and elevated intracranial pressures (particularly when very high and/or protracted).

Multimodal evoked potentials (MMEPs), as well as, electroencephalography (EEG) have both been used to assist with outcome prediction in patients in coma, as well as, the vegetative state. The role, if any, for static imaging as a means of outcome prediction remains debateable. Functional imaging on the other hand, may have a greater utility in this role; however, work is still in the early stages in this area of neuroscience.

The role of magnetic resonance spectroscopy (MRS) is yet to be defined in this group of patients, however, early research is promising, at least as a marker of injury severity and potential for emergence from VS. A variety of laboratory measures, including, but not limited to, ventricular CSF neurotransmitter metabolites, myelin basic proteins, creatine kinase and lactate levels, have also been studied relative to their predictive validity for neurologic outcome following severe TBI.

A variety of neuromedical factors have been found to correlate in a negative fashion with good outcome following severe TBI including certain types of high blood pressure, high acid levels, certain blood clotting problems, hypothalamic dysfunction, disturbances in motor reactivity, communicating hydrocephalus, late post--traumatic epilepsy (more than one seizure beyond the first week) and abnormal respiratory drive patterns. When analyzing prognostic data, it has been found that multifactorial/multidimensional analyses seem to allow for better outcome prediction accuracy.

The prognosis for emergence from the vegetative state is not only dependent upon the etiology of the insult, but also the time post-insult. Specifically, the longer from onset of injury, the worse the prognosis for emergence and once emerged the worse the prognosis for a good functional outcome.

The best prognosis is associated with recovery of consciousness within the first several days to two weeks. Recovery of consciousness after a month is associated with a higher probability of dependency for basic activities of daily living and mobility. The best recovery occurs in those patients who emerged from the vegetative state within six months with longer periods prior to emergence generally being associated with greater levels of neurological impairment, as well as, disability. Those patients recovering towards the end of a year typically have permanent, very severe, functional disability.

Differences exist relative to comparative prognosis across different groups of patients with brain injury depending upon numerous factors including the etiology of the brain insult. Assuming all other factors are constant, hypoxic/anoxic and/or ischemic brain injuries (HIBI) have a much poorer neurological and functional prognosis than traumatic brain injury without secondary brain insult regardless of the type of primary brain injury incurred i.e. diffuse axonal injury (DAI) versus focal injury, or both.

Clinicians should avoid making clinical and prognostic decisions based on literature garnered from studying TBI populations if the patient in question had a HIBI. Although there are some parallels between traumatically induced low level states and those that occur as a consequence of hypoxic injury, there are multiple major differences. Some of theses major differences include neuropathologic findings, associated clinical impairments, and short, as well as, long term neurologic and functional outcomes.


Interdisciplinary rehabilitative management of this patient population involves preventing potential morbidity issues as well as providing appropriate neuromedical and rehabilitative interventions to maximize potential neurologic and functional outcome. Rational neuromedical and rehabilitation management of this patient population has been delineated in several articles.

A full neuromedical work-up must be performed prior to labeling any patient as vegetative. Adequate understanding of the "late" neuromedical sequelae of traumatic brain injury is essential in the care and treatment of the this population. Medical conditions such as post-traumatic epilepsy, particularly of the non--convulsive type, post-traumatic hydrocephalus, neuroendocrine dysfunction, occult infection, late subdural hematomas, as well as, iatrogenic (e.g. physician caused) problems related to inappropriate use of pharmacological agents may all cause an individual to "look" vegetative when indeed they are not. Appropriate care should emphasize minimizing morbidity and treating any underlying condition(s) potentially suppressing neural recovery potential.

Researchers continue to examine various classes of drugs in an attempt to find agents that may hasten emergence from VS and/or optimize neurological improvement in those patients in MCS. Good nursing care with an emphasis on skin, respiratory, bowel/bladder care is crucial. Appropriate and timely prescription of adaptive equipment including seating and orthotics is paramount. Family involvement, education, and counseling should also be an integral part of any program dealing with persons in LLNSs.

The issue of whether so-called "coma stimulation" or structured sensory stimulation (SSS) can in any way actually be a negative factor in recovery has only recently been theorized. Firstly, coma stimulation is really a misnomer since most patients typically are not comatose.

Such issues of how stimulation may cause over-arousal and increase fatigue, decrease seizure threshold and/or increase maladaptive plasticity including spasticity, definitely need to be critically assessed. Nonetheless, the literature supporting a utility for such structured stimulation programs is lacking and most clinicians in the field would acknowledge that SSS probably has no effect on either rate or eventual plateau of neural recovery following acquired brain injury.

If sensory stimulation is offered, it should be done in a cost-efficient, ethical, and responsible fashion, not as the major component of the intervention program. SSS should be geared more towards tracking of neurobehavioral status than as a treatment intervention, per se. The exact role of other, more controversial interventions, such as neural stimulation and pharmacotherapy, for promoting recovery from VS remains unanswered but definitely warrants further research in a controlled, blinded fashion to establish the efficacy of these interventions .

As a community of health care providers, rehabilitation clinicians have sufficient experiential consensus, as well as, a growing base of prospective data regarding the efficacy of early and intensive rehabilitative treatment to minimize short, as well as, long-term morbidity, decrease health care costs, and optimize long-term functional outcomes.


Until recently, there was no literature that looked at specific morbidity risk factors and/or quality of care after severe brain injury in either vegetative or "minimally conscious" individuals. A recent study examined the long-term survival of children and adolescents after severe traumatic brain injury and found that the chief predictors of mortality were the level of independence in basic functional skills such as mobility and self-feeding.

For those individuals who had no mobility and were 6 months post-injury, the study found that their remaining life expectancy was predicted to be 15 years. At the most severe end of the LLNS disability spectrum, the permanent vegetative state, life expectancy has been shown to be at most 12 years without significant sex differences. Persons in MCS seem to have a similar albeit maybe slightly longer survival time. Studies of individuals in MCS show a propensity for only slightly longer survival times than those in the permanent vegetative state.

There are still limitations to what one can and cannot say about life expectancy in LLNSs. Appropriately conducted median survival time estimates must consider the historical record for past and current risk factors for medical morbidity, as well as, the frequency, type and severity of all infections and complications documented post-injury. Risk factors for medical morbidity such as poorly controlled generalized seizures, significant swallowing dysfunction and risk for aspiration, poor oral secretion control, absent or severely diminished gag or cough reflex, significant myostatic contractures and/or severe spasticity all have the potential to decrease life expectancy in and of themselves as related to their correlation with morbidity and therefore mortality.

Another factor to analyze is the temporal relationship of illness to injury, that is, is the individual in question more or less medically stable over time or not. Another seemingly crucial factor is the individual's relative degree of immobility and the implications for cardiopulmonary, gastrointestinal, musculoskeletal, integumentary and genitourinary morbidity and/or mortality. Neurologic deterioration over time generally is a harbinger for a shorter median survival time.


There is still much to be learned about LLNSs and in the last 5 years alone there have been significant inroads made into our understanding of these conditions. As we learn more about neurosalvage following severe brain injury, as well as, the neurorehabilitation of these disorders, we will hopefully be able to offer more to such patients and their families to not only improve their neurological outcome but also to add both years and quality to their lives.


  • Andrews, K. International working party on the management of the vegetative state: summary report. Brain Injury. 1996,10(11);797-806.
  • Andrews K, Murphy L, Munday R, Littlewood L.  (1996).  Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit.  BMJ.  6;313(7048):13-6.
  • Fins JJ. (2003).  Constructing an ethical stereotaxy for severe brain injury:  balancing risks, benefits and access.  Nat Rev Neurosci.  4(4):323-327.
  • Giacino JT, WHyte J. (2005).  The vegetative and minimally conscious states:  current knowledge and remaining questions.  JHTR.  20(1):30-50.
  • Giacino JT, Zasler ND, Whyte J, Katz DI, Glenn M, Andary M. (1995). Recommendations for use of unifrom nomenclature pertinent to patients with severe alterations in consciousness. Archives of Physical Medicineand Rehabilitation. 76.205-209.
  • Giacino JT & Zasler ND. (1995). Outcome following severe brain injury: the comatose, vegetative and minimally responsive patient. Journal of Head Trauma Rehabilitation. 10(1):40-56.
  • Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JR, Whyte J, & Zasler ND.  (2002). The minimally conscious state:  definition and diagnostic criteria.  Neurology.  58(3):349-353.  
  • Giacino J, Katz D, N Schiff.  (2006).  Low level neurologic states.  In:  N.D. Zasler, D. Katz, R. Zafonte (Eds.).  Brain Injury Medicine:  Principles and Practice.  New York.  Demos Publishers.
  • Giacino JT.  (2005).  The minimally conscious state:  defining the borders of consciousness.  Prog Brain Res.  150:381-395.
  • Gigli GL, Zasler ND. (2004).  Life-sustaining treatments in vegetative state:  scientific advances and ethical dilemmas.  NeuroRehabilitation. 19(4).
  • Jennett B. (2002). The Vegetative State.  Medical Facts, Ethical and Legal Dilemmas.  Cambridge.  Cambridge University Press.
  • Lammi MH, Smith VH, Tate RL, Taylor CM.  (2005).  The minimally conscious state and recovery potential:  a follow-up study 2 to 5 years after traumatic brain injury.  Arch Phys Med Rehabil.  86(4):746-754, 2005.
  • Laureys S, Antoine S, boly M, et al.  (2002).  Brain function in the vegetative state.  Acta Neurol Belg.  102(4):177-185.
  • Laureys S.  (2005).  The neural correlate of (un)awareness:  lessons from the vegetative state.  Trends Cogn Sci.  9(12):556-559.
  • Multi-society task force on PVS. (1994). Medical aspects of the persistent vegetative state (first of two parts). NEJM.  330(21):1499-1508.
  • Multi-society task force on PVS. (1994). Medical aspects of the persistent vegetative state (second of two parts). NEJM. 330(22):1572-1579.
  • Ng YS, Chua KS.  (2005).  States of severely altered consciousness:  clinical characteristics, medical complications and functional outcome after rehabilitation.  NeuroRehabilitation.  20(2):97-105.
  • Plum F & Posner JB. (1983). The diagnosis of stupor and coma. 3rd edition. Philadelphia, F .A. Davis. 
  • Schiff ND, Ribary U, Moreno DR, et al.  (2002).  Residual cerebral activity and behavioral fragments can remain in the persistently vegetative brain.  Brain.  125(Pt 6):12210-1234.
  • Schiff ND.  (2005).  Modeling the minimally conscious state:  measurements of brain function and therapeutic possibilities.  Prog Brain Res.  150:473-493.
  • Shavelle RM, Strauss DJ, Day SM, Ojdana KA.  Life Expectancy.  In: N.D. Zasler, D. Katz, R. Zafonte (Eds.).  Brain Injury Medicine:  Principles and Practice. Second Edition.  New York.  Demos Publishers.  2006.
  • Whyte J, Katz D, Long D, et al.  (2005).  Predictors of outcome in porlonged post-traumatic disorders of consciousness and assessment of medication effects :  a multicenter study.  Arch Phys Med Rehabil.  86(3):453-462.
  • Working Party of the Royal College of Physicians.  (2003).  The vegetative state:  Guidance on diagnosis and management.  Royal College of Physicians.  England.  Code Pub 15112070.  ISBN 1 86016 186 3.  A4 report.
  • Zasler ND, Cantor IV.  ( Winter 2003-2004).  Medicolegal aspects of severe traumatic brain injury.  The Journal of The Virginia Trial Lawyers Association.26-39.
  • Zasler ND. (2005):  Forensic assessment issues in low level neurological states.  Neuropsychological Rehabilitation.  15(3/4), 251–256.
  • Zasler ND, Kreutzer JS, Taylor D.  (1991).  Coma Recovery and Coma Stimulation: A Critical Review. NeuroRehabilitation. 1(3):33-40.