No abstract

BackgroundSome patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS).DiscussionMany clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name.ConclusionSince after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).

Sleep disorders are frequent (18%–23%) and constitute a major risk factor for psychiatric, cardiovascular, metabolic or hormonal co-morbidity and mortality. Low social status or income, unemployment, life events such as divorce, negative lifestyle habits, and professional requirements (e.g., shift work) are often associated with sleep problems. Sleep disorders affect the quality of life and impair both professional and non-professional activities. Excessive daytime drowsiness resulting from sleep disorders impairs efficiency and safety at work or on the road, and increases the risk of accidents. Poor sleep (either professional or voluntary) has detrimental effects comparable to those of major sleep disorders, but is often neglected. The high incidence and direct/indirect healthcare and welfare costs of sleep disorders and poor sleep currently constitute a major medical problem. Investigation, monitoring and strategies are needed in order to prevent/reduce the effects of these disorders.

BackgroundDespite evidence from neuroimaging research, diagnosis and early prognosis in the vegetative (VS/UWS) and minimally conscious (MCS) states still depend on the observation of clinical signs of responsiveness. Multiple testing has documented a systematic variability during the day in the incidence of established signs of responsiveness. Spontaneous fluctuations of the Coma Recovery Scale-revised (CRS-r) scores are conceivable.MethodsWe retrospectively analyzed the CRS-r repeatedly administered to 7 VS/UWS and 12 MCS subjects undergoing systematic observation during a conventional 13 weeks. rehabilitation plan.ResultsThe CRS-r global, visual and auditory scores were found higher in the morning than at the afternoon administration in both VS/UWS and MCS subgroups over the entire period of observation. The probability for a VS/UWS subject of being classified as MCS at the morning testing at least once during the 13 weeks. observation was as high as 30 %, i.e., compatible with the reported misdiagnosis rate between the two clinical conditions.ConclusionsMultiple CRS-r testing is advisable to minimize the risk of misclassification; estimates of spontaneous variability could be used to characterize with greater accuracy patients with disorder of consciousness and possibly help optimize the rehabilitation plan.

Visual pursuit marks substantial recuperation from a vegetative state and evolution into a minimally-conscious state, but its incidence in different studies suggests some unreliability in contrast with its established prognostic relevance. Subjects in vegetative (n=9) or minimally-conscious (n=13) states were tested for visual pursuit 6 times/day (9:30, 10:30, and 11:30 am, and 2:00, 3:00, and 4.00 pm, for a total of 132 determinations). Visual pursuit was observed at all testing times in 8 minimally-conscious patients, and never in 5 subjects in a vegetative state. Its incidence per subject ranged from 50-100% of testing times in the minimally-conscious state (83±23%), and 0-33% in a vegetative state (7%±12), with spontaneous fluctuations during the day and maximal levels at 10.30 am and 3.00 pm, and was never observed at the post-prandial time point (2:00 pm). The overall chance of observing visual tracking at least once during the day was ∼33% in the vegetative state, whereas that of not observing it in the minimally-conscious state was ∼38%. These percentages are congruent with the reported misdiagnosis rate between the two conditions, and document spontaneous variability possibly related to circadian rhythms.

Electrophysiological evidence at a cellular level and in vivo macroelectrode recordings converge in indicating a degree of specificity of acetylcholine action in vision. Acetylcholine (ACh) function is also thought to play a significant role in memory, learning and other cognitive processes. In this respect, ACh action is suggested to serve in both sensory and cognitive processes. The pharmacological blocking of brain muscarinic transmission has been proposed as a model of geriatric memory impairment and Alzheimer's dementia. Visual electrophysiological testing is deemed of diagnostic specificity for this disease. ACh brain neurotransmission, however, mostly contributes to the modulation of nonspecific aspects of cognition, such as arousal or attention. Alzheimer's dementia results from complex neuron alterations [which also affect muscarinic receptors among other (sub)cellular structures] rather than simply reflecting ACh impoverishment. A substantial loss of retinal ganglion cells is documented in patients with Alzheimer's disease and is consistent with electrophysiological observations. However, it is unclear to what extent the dysfunction of the visual system observable in Alzheimer's dementia is qualitatively different from that occurring spontaneously during aging. The dissimilarities between the effect of acute muscarinic blocking (e.g. by scopolamine) and dementia outnumber the similarities. Accordingly, the conventional ACh agonist-antagonist model of dementia now appears questionable, and replacement treatment with compounds enhancing ACh function proved disappointing. It is suggested that (nonspecific) ACh action becomes function-specific, as determined by the architecture of local brain circuits in which it is involved.

There has been clinical and experimental evidence that cholinergic compounds and precursors of choline are potentially useful in the treatment of dementia. Anticholinergic compounds have also been proposed as a possible acute model for pharmaco-EEG studies focussed on CNS aging. Single doses of scopolamine (0.25–0.75 mg i.m.) and a matching placebo were administered to 8 young healthy volunteers. Quantitative EEG recordings and neuropsychological testing were performed in baseline conditions prior to and 30, 90 and 120 min after drug administration. Scopolamine induced a dose-related increase of relative power in low- and high-frequency components and a decrease in the range 8.0–13.5 Hz and in total signal power. These modifications were found to be limited to the posterior scalp electrode derivations and were observed from the 90-min control onwards. Concomitantly, there was a significant impairment in the subjects’ response to neuropsychological testing after the administration of 0.50 and 0.75 mg of scopolamine. At a dose of 0.75 mg, volunteers complained about subjective symptoms which were definitely unpleasant. The effects of this dose on the EEG and the neuropsychological status did not differ significantly from those observed after a dose of 0.50 mg. As regards dose and tolerance, 0.50 mg of scopolamine administered intramuscularly appears to be a suitable dose for pharmaco-EEG studies.

No abstract