The term persistent vegetative state was coined in 1972 by Scottish spinal surgeon Bryan Jennett and American neurologist Fred Plum to describe a syndrome that seemed to have been made possible by medicine's increased capacities to keep patients' bodies alive.
A 23-year-old woman in a vegetative state after a severe brain injury due to a car accident in 2005 was able to communicate with a team of British researchers at Cambridge University in England via functional magnetic resonance imaging.
The vegetative state is a chronic or long-term condition. This condition differs from a persistent vegetative state (PVS, a state of coma that lacks both awareness and wakefulness) since patients have awakened from coma, but still have not regained awareness. In the vegetative state patients can open their eyelids occasionally and demonstrate sleep-wake cycles. They also completely lack cognitive function. The vegetative state is also called coma vigil. The continuing vegetative state describes a patient's diagnosis prior to confirmation of the permanence of the condition. The permanent vegetative state occurs when the vegetative state is deemed permanent; a prediction is being made that the patient will never recover awareness. This prediction cannot be made with absolute certainty. However, the chances of regaining awareness diminish considerably as the time spent in the vegetative state increases (Royal College of Physicians, 1996).
This typology distinguishes various stages of the condition rather than using one term for them all. In his most recent book The Vegetative State, Jennett himself adopts this usage, on the grounds that "the 'persistent' component of this term ... may seem to suggest irreversibility". The Australian National Health and Medical Research Council has suggested "post coma unresponsiveness" as an alternative term.
PVS patients' eyes might be in a relatively fixed position, or track moving objects, or move in a disconjugate (i.e. completely unsynchronized) manner. They may experience sleep-wake cycles, or be in a state of chronic wakefulness. They may exhibit some behaviors that can be construed as arising from partial consciousness, such as grinding their teeth, swallowing, smiling, shedding tears, grunting, moaning, or screaming without any apparent external stimulus.
Individuals in PVS are seldom on any life-sustaining equipment other than a feeding tube because the brainstem, the center of vegetative functions (such as heart rate and rhythm, respiration, gastrointestinal activity), is relatively intact (Emmett, 1989).
Medical books (such as Lippincott, Williams, and Wilkins. (2007). In A Page: Pediatric Signs and Symptoms ) describe several potential causes of PVS, which are as follows:
In addition, these authors claim that doctors sometimes use the mnemonic device AEIOU-TIPS to recall portions of the differential diagnosis: Alcohol ingestion and acidosis, Epilepsy and encephalopathy, Infection, Opiates, Uremia, Trauma, Insulin overdose or inflammatory disorders, Poisoning and psychogenic causes, and Shock.
For example, PET studies have shown the identification of residual cognitive function in persistent vegetative state. That is, an external stimulation, such as a painful stimulus, still activates 'primary' sensory cortices in these patients but these areas are functionally disconnected from 'higher order' associative areas needed for awareness. These results show that parts of the cortex are indeed still functioning in 'vegetative' patients (Matsuda et al, 2003).
In addition, other PET studies have revealed preserved and consistent responses in predicted regions of auditory cortex in response to intelligible speech stimuli. Moreover, a preliminary fMRI examination revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension (Boly, 2004).
Furthermore, several studies have used PET to assess the central processing of noxious somatosensory stimuli in patients in PVS. Noxious somatosensory stimulation activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices (Laureys et al, 2002).
Also, there is evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in PVS with different behavioral features, researchers employed PET, MRI and magnetoencephalographic (MEG) responses to sensory stimulation. In three of the five patients, co-registered PET/MRI correlate areas of relatively preserved brain metabolism with isolated fragments of behavior. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30–40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50–80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioral patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioral fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical– pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains (Schiff et al, 2002).
Can there be conscious awareness in vegetative state? Three completely different aspects of this issue should be distinguished. First, some patients can be conscious simply because they are misdiagnosed (see above). In fact, they are not in vegetative state. Second, sometimes a patient was correctly diagnosed but, then, examined during a beginning recovery. Third, perhaps some day the very notion of the vegetative state will change so as to include elements of conscious awareness. Inability to disentangle these three cases leads to confusion. An example of such confusion is the response to a recent experiment using magnetic resonance imaging which revealed that a woman diagnosed with PVS was able to activate predictable portions of her brain in response to the tester's requests that she imagine herself playing tennis or moving from room to room in her house. The brain activity in response to these instructions was indistinguishable from those of healthy patients. Because such activations can be obtained only if a patient has clear awareness and concentrated attention, the diagnosis of PVS was obviously an error. Therefore, the experiment did not show awareness in vegetative state in any reasonable sense of the word; rather, it showed that magnetic resonance imaging, combined with sophisticated stimulation, can effectively be used to disclose major diagnostic errors.
There are two dimensions of recovery from a persistent vegetative state: recovery of consciousness and recovery of function. Recovery of consciousness can be verified by reliable evidence of awareness of self and the environment, consistent voluntary behavioral responses to visual and auditory stimuli, and interaction with others. Recovery of function is characterized by communication, the ability to learn and to perform adaptive tasks, mobility, self-care, and participation in recreational or vocational activities. Recovery of consciousness may occur without functional recovery, but functional recovery cannot occur without recovery of consciousness (Ashwal, 1994).
As of today, no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based medicine. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or methylphenidate. Promising results have been reported on dopaminergic drugs, particularly amantadine. Presently the first randomized controlled trial amantadine versus placebo is running; its results have not been published yet. Surgical methods such as deep brain stimulation are rarely used. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, etc. Below are some details related to treatments that have demonstrated some hope.
Additionally, stroke victims and patients with head injuries or brain damage following oxygen deprivation, such as near-drowning victims, have reported significant improvements in speech, motor functions, and concentration after treatment with zolpidem.
A clinical trial of zolpidem involving over 360 PVS patients worldwide is currently underway, and 60% of these patients are showing signs of improvement, although no results have yet been published.
There is one other published case series on the long-term effects of zolpidem on patients in PVS, also authored by Nel & Clauss. The first patient, "L", is a 31 year old male who, before treatment with zolpidem, had been in PVS for three years with a Glasgow Coma Scale of 9. They report that after receiving 10mg of zolpidem, L is able to engage in meaningful conversation. The maximum effect of the zolpidem is seen one hour after application and wears off after about four hours. By the date of publication in 2006, L had been receiving zolpidem therapy for six years, with no decrease in the effectiveness of treatment, and some gradual long-term improvement in short- and long-term memory. The other two patients in the case series were male, of similar age, and had similar though somewhat lessened responses to zolpidem — the zolpidem worked maximally one hour after application, its effects wore off after four hours, and there was no decrease in effectiveness after several years of daily use.
As yet, no scientific studies have been published on the effectiveness of zolpidem as a treatment for PVS.
Case 1 describes a 14 year old boy who, three months after his trauma, could not follow moving objects with his eyes and experienced tremor-like involuntary movements as well as hypertonicity (increased tension of the muscles, meaning the muscle tone is abnormally rigid, hampering proper movement). Levodopa was recommended to relieve the patient’s parkinsonian features. Surprisingly, after nine days of treatment the patient’s involuntary movements were reduced and he began to respond toward voices. Three months after treatment, he was able to walk and obtained the intelligence of an elementary school child. One year after his trauma, he was able to walk to high school by himself. Case 2 involves a young adult who underwent deep brain stimulation one year after the trauma and showed no improvement. Levodopa was administered and one year later, once his tubes were removed, he said, “I want to eat sushi and drink beer!” Case 3 describes a middle-aged man who experienced spasticity of his extremities, was administered levodopa, and was able to say his name and address correctly after only two months. After neurological evaluation, all three cases revealed asymmetrical rigidity or tremor and presynaptic damage in the dopaminergic (uses dopamine as neurotransmitter) systems. In conclusion, levodopa should be considered for patients in a persistent vegetative state with atypical features in their limbs and who have MRI evidence of lesions in the dopaminergic pathway, particularly presynaptic lesions in areas such as the substantia nigra or ventral tegmentum. Data shows that only 6% of adult patients recover after being in a vegetative state for six to twelve months. This poor recovery rate demonstrates the significance in the rapid recovery of patients that begin levodopa treatment, particularly in those who were in a vegetative state for almost a year.
This article contains text from the NINDS public domain pages on TBI at http://www.ninds.nih.gov/health_and_medical/disorders/tbi_doc.htm and http://www.ninds.nih.gov/health_and_medical/pubs/tbi.htm