Marie-Elisabeth Faymonville

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Restoration of thalamocortical connectivity after recovery from persistent vegetative state

By use of H2(15)O positron emission tomography we have shown that functional connectivity between intralaminar thalamic nuclei and prefrontal and anterior cingulate cortices was altered during vegetative state but not after recovery of consciousness.

Perception of pain in the minimally conscious state with PET activation: an observational study.

BACKGROUND Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. METHODS We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. FINDINGS In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. INTERPRETATION Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Cerebral processing in the minimally conscious state

We studied a patient in a minimally conscious state using PET and cognitive evoked potentials. Cerebral metabolism was below half of normal values. Auditory stimuli with emotional valence (infant cries and the patient’s own name) induced a much more widespread activation than did meaningless noise; the activation pattern was comparable with that previously obtained in controls. Cognitive potentials showed preserved P300 responses to the patient’s own name.

Psychological approaches during conscious sedation. Hypnosis versus stress reducing strategies: a prospective randomized study

&NA; Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological approaches for reducing perioperative discomfort during conscious sedation for plastic surgery. Sixty patients scheduled for elective plastic surgery under local anesthesia and intravenous sedation (midazolam and alfentanil upon request) were included in the study after providing informed consent. They were randomly allocated to either stress reducing strategies (control: CONT) or hypnosis (HYP) during the entire surgical procedure. Both techniques were performed by the same anesthesiologist (MEF). Patient behavior was noted during surgery by a psychologist, the patient noted anxiety, pain, perceived control before, during and after surgery, and postoperative nausea and vomiting (PONV). Patient satisfaction and surgical conditions were also recorded. Peri‐ and postoperative anxiety and pain were significantly lower in the HYP group. This reduction in anxiety and pain were achieved despite a significant reduction in intraoperative requirements for midazolam and alfentanil in the HYP group (alfentanil: 8.7±0.9 &mgr;g kg−1/h−1 vs. 19.4±2 &mgr;g kg−1/h−1, P<0.001; midazolam: 0.04±0.003 mg kg−1/h−1 vs. 0.09±0.01 mg kg−1/h−1, P<0.001). Patients in the HYP group reported an impression of more intraoperative control than those in the CONT group (P<0.01). PONV were significantly reduced in the HYP group (6.5% vs. 30.8%, P<0.001). Surgical conditions were better in the HYP group. Less signs of patient discomfort and pain were observed by the psychologist in the HYP group (P<0.001). Vital signs were significantly more stable in the HYP group. Patient satisfaction score was significantly higher in the HYP group (P<0.004). This study suggests that hypnosis provides better perioperative pain and anxiety relief, allows for significant reductions in alfentanil and midazolam requirements, and improves patient satisfaction and surgical conditions as compared with conventional stress reducing strategies support in patients receiving conscious sedation for plastic surgery.

The cognitive modulation of pain: hypnosis- and placebo-induced analgesia.

Nowadays, there is compelling evidence that there is a poor relationship between the incoming sensory input and the resulting pain sensation. Signals coming from the peripheral nervous system undergo a complex modulation by cognitive, affective, and motivational processes when they enter the central nervous system. Placebo- and hypnosis-induced analgesia form two extreme examples of how cognitive processes may influence the pain sensation. With the advent of modern brain imaging techniques, researchers have started to disentangle the brain mechanisms involved in these forms of cognitive modulation of pain. These studies have shown that the prefrontal and anterior cingulate cortices form important structures in a descending pathway that modulates incoming sensory input, likely via activation of the endogenous pain modulatory structures in the midbrain periaqueductal gray. Although little is known about the receptor systems involved in hypnosis-induced analgesia, studies of the placebo response suggest that the opiodergic and dopaminergic systems play an important role in the mediation of the placebo response.

Psychological approaches during dressing changes of burned patients: a prospective randomised study comparing hypnosis against stress reducing strategy

A prospective study was designed to compare two psychological support interventions in controlling peri-dressing change pain and anxiety in severely burned patients. Thirty patients with a total burned surface area of 10-25%, requiring a hospital stay of at least 14 days, were randomised to receive either hypnosis or stress reducing strategies (SRS) adjunctively to routine intramuscular pre-dressing change analgesia and anxiolytic drugs. Visual analogue scale (VAS) scores for anxiety, pain, pain control and satisfaction were recorded at 2-day intervals throughout the 14-day study period, before, during and after dressing changes. The psychological assistance was given on days 8 and 10 after hospital admission. The comparison of the two treatment groups indicated that VAS anxiety scores were significantly decreased before and during dressing changes when the hypnotic technique was used instead of SRS. No difference was observed for pain, pain control and satisfaction, although VAS scores were always better in the hypnosis group. The study also showed that, overall, psychological support interventions reduced pain and increased patient satisfaction. These results confirm the potential benefits of psychological assistance during dressing changes in burned patients.

Pain and non-pain processing during hypnosis: A thulium-YAG event-related fMRI study

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation.

Consciousness and cerebral baseline activity fluctuations.

The origin of within‐subject variability in perceptual experiments is poorly understood. We here review evidence that baseline brain activity in the areas involved in sensory perception predict subsequent variations in sensory awareness. We place these findings in light of recent findings on the architecture of spontaneous BOLD fluctuations in the awake human brain, and discuss the possible origins of the observed baseline brain activity fluctuations. Hum Brain Mapp 2008.

Organ Procurement After Euthanasia: Belgian Experience

Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness or accident. Between 2005 and 2007, 4 patients (3 in Antwerp and 1 in Liège) expressed their will for organ donation after their request for euthanasia was granted. Patients were aged 43 to 50 years and had a debilitating neurologic disease, either after severe cerebrovascular accident or primary progressive multiple sclerosis. Ethical boards requested complete written scenario with informed consent of donor and relatives, clear separation between euthanasia and organ procurement procedure, and all procedures to be performed by senior staff members and nursing staff on a voluntary basis. The euthanasia procedure was performed by three independent physicians in the operating room. After clinical diagnosis of cardiac death, organ procurement was performed by femoral vessel cannulation or quick laparotomy. In 2 patients, the liver, both kidneys, and pancreatic islets (one case) were procured and transplanted; in the other 2 patients, there was additional lung procurement and transplantation. Transplant centers were informed of the nature of the case and the elements of organ procurement. There was primary function of all organs. The involved physicians and transplant teams had the well-discussed opinion that this strong request for organ donation after euthanasia could not be waived. A clear separation between the euthanasia request, the euthanasia procedure, and the organ procurement procedure is necessary.