Trigeminal nerve electrical stimulation: An effective arousal treatment for loss of consciousness.

BACKGROUND: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness. METHODS: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH). RESULTS: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene microarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment. CONCLUSION: This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.

Dynamics of recovery from anaesthesia-induced unconsciousness across primate neocortex.

How the brain recovers from general anaesthesia is poorly understood. Neurocognitive problems during anaesthesia recovery are associated with an increase in morbidity and mortality in patients. We studied intracortical neuronal dynamics during transitions from propofol-induced unconsciousness into consciousness by directly recording local field potentials and single neuron activity in a functionally and anatomically interconnecting somatosensory (S1, S2) and ventral premotor (PMv) network in primates. Macaque monkeys were trained for a behavioural task designed to determine trial-by-trial alertness and neuronal response to tactile and auditory stimulation. We found that neuronal dynamics were dissociated between S1 and higher-order PMv prior to return of consciousness. The return of consciousness was distinguishable by a distinctive return of interregionally coherent beta oscillations and disruption of the slow-delta oscillations. Clustering analysis demonstrated that these state transitions between wakefulness and unconsciousness were rapid and unstable. In contrast, return of pre-anaesthetic task performance was observed with a gradual increase in the coherent beta oscillations. We also found that recovery end points significantly varied intra-individually across sessions, as compared to a rather consistent loss of consciousness time. Recovery of single neuron multisensory responses appeared to be associated with the time of full performance recovery rather than the length of recovery time. Similar to loss of consciousness, return of consciousness was identified with an abrupt shift of dynamics and the regions were dissociated temporarily during the transition. However, the actual dynamics change during return of consciousness is not simply an inverse of loss of consciousness, suggesting a unique process.

Disentangling conscious from unconscious cognitive processing with event-related EEG potentials.

By looking for properties of consciousness, cognitive neuroscience studies have dramatically enlarged the scope of unconscious cognitive processing. This emerging knowledge inspired the development of new approaches allowing clinicians to probe and disentangle conscious from unconscious cognitive processes in non-communicating brain-injured patients both in terms of behaviour and brain activity. This information is extremely valuable in order to improve diagnosis and prognosis in such patients both at acute and chronic settings. Reciprocally, the growing observations coming from such patients suffering from disorders of consciousness provide valuable constraints to theoretical models of consciousness. In this review we chose to illustrate these recent developments by focusing on brain signals recorded with EEG at bedside in response to auditory stimuli. More precisely, we present the respective EEG markers of unconscious and conscious processing of two classes of auditory stimuli (sounds and words). We show that in both cases, conscious access to the corresponding representation (e.g.: auditory regularity and verbal semantic content) share a similar neural signature (P3b and P600/LPC) that can be distinguished from unconscious processing occurring during an earlier stage (MMN and N400). We propose a two-stage serial model of processing and discuss how unconscious and conscious signatures can be measured at bedside providing relevant informations for both diagnosis and prognosis of consciousness recovery. These two examples emphasize how fruitful can be the bidirectional approach exploring cognition in healthy subjects and in brain-damaged patients.

Changes in effective connectivity of sensorimotor rhythms in thalamocortical circuits during the induction and recovery of anesthesia in mice.

The thalamocortical network serves a role in both consciousness and sensorimotor processing. However, little is known regarding how changes in conscious states, via induction of and recovery from anesthesia, affect the processing of sensorimotor information in the thalamocortical network. To address this, we investigated the dynamics of causal interactions among sensorimotor rhythms (SMR; frequency range of 3-12Hz) across the thalamocortical network during transitions into and out of ketamine-induced unconsciousness. Two local field potentials from the ventral lateral and ventrobasal thalamic nuclei, as well as two intracranial electroencephalography signals from the primary sensory and primary motor regions, were recorded in 10 mice. Spectral Granger causality analysis revealed two distinct frequency-specific patterns in sensorimotor rhythms. For the low-frequency (3-6.5Hz) SMR, loss of consciousness evoked causal influences directed from the cortex to the thalamus. For the high-frequency (6.5-12Hz) SMR, causal influences from the primary sensory cortex to other regions during the conscious period were abruptly altered by loss of consciousness and gradually regenerated following recovery of consciousness. The results of the present study indicate that anesthesia alters the flow of sensorimotor information in the thalamocortical network and may provide evidence of the neural basis of loss and recovery of sensorimotor function associated with anesthesia.

Changes in the Bispectral Index in Response to Loss of Consciousness and No Somatic Movement to Nociceptive Stimuli in Elderly Patients.

BACKGROUND: Bispectral index (BIS) is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil. METHODS: This study was performed on 52 elderly patients (aged 65-78 years) and 52 young patients (aged 25-58 years), American Society of Anesthesiologists physical status I or II. Anesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, [TENS]) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil predicted effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated. RESULTS: BISLOCin elderly group was higher than that in young patient group (65.4 ± 9.7 vs. 57.6 ± 12.3) (t = 21.58, P < 0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6 ± 0.3 µg/ml in elderly patients, which was significantly lower than that in young patients (2.3 ± 0.5 µg/ml) (t = 7.474, P < 0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t = 8.902 and t = 8.019, P < 0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOSwas the same as the BISLOCin elderly patients (65.6 ± 10.7 vs. 65.4 ± 9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS. CONCLUSION: In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually. TRIAL REGISTRATION: CTRI Reg. No: ChiCTR-OOC-14005629; http://www.chictr.org.cn/showproj.aspx?proj=9875.

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep.

During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.

Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness.

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.

[BIS values were useful on the evaluation of consciousness recovery in acute Vegetamin-A poisoning: report of a case].

A 37-year-old man was admitted to our hospital with acute phenobarbital poisoning. On arrival, he was in deep coma with respiro-circulatory depressions. The serum concentration of the agent was elevated to 149.04 µg/mL which was consistent with a lethal concentration level. He underwent a gastric lavage, administration of activated charcoal, urinary alkalinazation and bowel irrigation. Respiro-circulatory status was recovered rapidly, while the serum concentration of phenobarbital did not decrease smoothly. Although the concentration of the agent decreased to 77.07 µg/mL that should be a comatose level, BIS values were gradually elevated, and then eventually the patient regained his consciousness. Because he was a chronic user of Vegetamin-A containing phenobarbital, the serum level might not have been correlated with symptoms. BIS values were highly reflective of the consciousness level, so it could be a useful indicator for predicting the consciousness levels of patients in deep coma with acute poisoning from hypnotic agents.

Thalamocortical mechanisms for the anteriorization of α rhythms during propofol-induced unconsciousness.

As humans are induced into a state of general anesthesia via propofol, the normal alpha rhythm (8-13 Hz) in the occipital cortex disappears and a frontal alpha rhythm emerges. This spatial shift in alpha activity is called anteriorization. We present a thalamocortical model that suggests mechanisms underlying anteriorization. Our model captures the neural dynamics of anteriorization when we adjust it to reflect two key actions of propofol: its potentiation of GABA and its reduction of the hyperpolarization-activated current Ih. The reduction in Ih abolishes the occipital alpha by silencing a specialized subset of thalamocortical cells, thought to generate occipital alpha at depolarized membrane potentials (>-60 mV). The increase in GABA inhibition imposes an alpha timescale on both the cortical and thalamic portions of the frontal component that are reinforced by reciprocal thalamocortical feedback. Anteriorization can thus be understood as a differential effect of anesthetic drugs on thalamic nuclei with disparate spatial projections, i.e.: (1) they disrupt the normal, depolarized alpha in posterior-projecting thalamic nuclei while (2) they engage a new, hyperpolarized alpha in frontothalamic nuclei. Our model generalizes to other anesthetics that include GABA as a target, since the molecular targets of many such anesthetics alter the model dynamics in a manner similar to that of propofol.

Characterization of phase transition in the thalamocortical system during anesthesia-induced loss of consciousness.

The thalamocortical system plays a key role in the breakdown or emergence of consciousness, providing bottom-up information delivery from sensory afferents and integrating top-down intracortical and thalamocortical reciprocal signaling. A fundamental and so far unanswered question for cognitive neuroscience remains whether the thalamocortical switch for consciousness works in a discontinuous manner or not. To unveil the nature of thalamocortical system phase transition in conjunction with consciousness transition, ketamine/xylazine was administered unobtrusively to ten mice under a forced working test with motion tracker, and field potentials in the sensory and motor-related cortex and thalamic nuclei were concomitantly collected. Sensory and motor-related thalamocortical networks were found to behave continuously at anesthesia induction and emergence, as evidenced by a sigmoidal response function with respect to anesthetic concentration. Hyperpolarizing and depolarizing susceptibility diverged, and a non-discrete change of transitional probability occurred at transitional regimes, which are hallmarks of continuous phase transition. The hyperpolarization curve as a function of anesthetic concentration demonstrated a hysteresis loop, with a significantly higher anesthetic level for transition to the down state compared to transition to the up state. Together, our findings concerning the nature of phase transition in the thalamocortical system during consciousness transition further elucidate the underlying basis for the ambiguous borderlines between conscious and unconscious brains. Moreover, our novel analysis method can be applied to systematic and quantitative handling of subjective concepts in cognitive neuroscience.

Deep brain stimulation: Subthalamic nucleus electrophysiological activity in awake and anesthetized patients.

OBJECTIVE: The purpose of this study was to evaluate changes in subthalamic nucleus (STN) neuronal activity in Parkinson's disease (PD) patients during deep brain stimulation (DBS) surgery under general anesthesia, and to compare these data with those recorded in the same subjects during previous surgery under local anesthesia. METHODS: Five patients with advanced PD, who had previously undergone bilateral STN-DBS under local anesthesia, underwent re-implantation under general anesthesia (with an anesthetic protocol based on the intravenous infusion of remifentanyl and ketamine) owing to surgical device complications. The microelectrode recording (MER) data obtained were analyzed by an off-line spike-sorting software. Neurophysiological data (number of spikes detected, mean firing rate, pause index and burst index) obtained under local and general anesthesia were then evaluated and compared by means of statistical analysis. RESULTS: We found no statistically significant difference between the first and second surgical procedures in any of the neurophysiological parameters analyzed. CONCLUSIONS: Bilateral STN-DBS for advanced PD with MER guidance is possible and reliable under a ketamine-based anesthetic protocol. SIGNIFICANCE: General anesthesia can be proposed for those patients who do not accept an "awake surgery" for clinical reasons, such as excessive fear, poor cooperation or severe "off"-medication effects.

Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.

The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.

Propofol and etomidate depress cortical, thalamic, and reticular formation neurons during anesthetic-induced unconsciousness.

BACKGROUND: The sites where anesthetics produce unconsciousness are not well understood. Likely sites include the cerebral cortex, thalamus, and reticular formation. We examined the effects of propofol and etomidate on neuronal function in the cortex, thalamus, and reticular formation in intact animals. METHODS: Five cats had a recording well and electroencephalogram screws placed under anesthesia. After a 5-day recovery period, the cats were repeatedly studied 3 to 4 times per week. Neuronal (single-unit) activity in the cerebral cortex (areas 7, 18 and 19), thalamus (ventral posterolateral and ventral posteromedial nuclei and medial geniculate body), and reticular formation (mesencephalic reticular nucleus and central tegmental field) was recorded before, during, and after infusion of either propofol or etomidate. Cortical neuronal action potentials were analyzed separately as either regular spiking neurons or fast spiking neurons. RESULTS: Propofol and etomidate decreased the spontaneous firing rate of cortical neurons by 37% to 41%; fast spiking neurons and regular spiking neurons were similarly affected by the anesthetics. The neuronal firing rate in the thalamus and reticular formation decreased 30% to 49% by propofol and etomidate. The electroencephalogram shifted from a low-amplitude, high-frequency pattern to a high-amplitude, low-frequency pattern during drug infusion suggesting an anesthetic effect; peak power occurred at 12 to 13 Hz during propofol infusion. There were 2 major peaks during etomidate anesthesia: one at 12 to 14 Hz and another at 7 to 8 Hz. The cats were heavily sedated, with depressed corneal and whisker reflexes; withdrawal to noxious stimulation remained intact. CONCLUSION: These data show that neurons in the cortex, thalamus, and reticular formation are similarly depressed by propofol and etomidate. Although anesthetic depression of neuronal activity likely contributes to anesthetic-induced unconsciousness, further work is needed to determine how anesthetic effects at these sites interact to produce unconsciousness.

Application of nonlinear dynamics analysis in assessing unconsciousness: a preliminary study.

OBJECTIVES: To quantify the degree of unconsciousness with EEG nonlinear analysis and investigate the change of EEG nonlinear properties under different conditions. METHODS: Twenty-one subjects in persistent vegetative state (PVS), 16 in minimally conscious state (MCS) and 30 normal conscious subjects (control group) with brain trauma or stroke were involved in the study. EEG was recorded under three conditions: eyes closed, auditory stimuli and painful stimuli. EEG nonlinear indices such as Lempel-Ziv complexity (LZC), approximate entropy (ApEn) and cross-approximate entropy (cross-ApEn) were calculated for all the subjects. RESULTS: The PVS subjects had the lowest nonlinear indices followed by the MCS subjects and the control group had the highest. The PVS and MCS group had poorer response to auditory and painful stimuli than the control group. Under painful stimuli, nonlinear indices of subjects who recovered (REC) increased more significantly than non-REC subjects. CONCLUSIONS: With EEG nonlinear analysis, the degree of suppression for PVS and MCS could be quantified. The changes of brain function for unconscious subjects could be captured by EEG nonlinear analysis. SIGNIFICANCE: EEG nonlinear analysis could characterise the changes of brain function for unconscious state and might have some value in predicting prognosis of unconscious subjects.

Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical-subcortical synchronization.

Loss of consciousness (LOC) is a dramatic clinical manifestation of temporal lobe seizures. Its underlying mechanism could involve altered coordinated neuronal activity between the brain regions that support conscious information processing. The consciousness access hypothesis assumes the existence of a global workspace in which information becomes available via synchronized activity within neuronal modules, often widely distributed throughout the brain. Re-entry loops and, in particular, thalamo-cortical communication would be crucial to functionally bind different modules together. In the present investigation, we used intracranial recordings of cortical and subcortical structures in 12 patients, with intractable temporal lobe epilepsy (TLE), as part of their presurgical evaluation to investigate the relationship between states of consciousness and neuronal activity within the brain. The synchronization of electroencephalography signals between distant regions was estimated as a function of time by using non-linear regression analysis. We report that LOC occurring during temporal lobe seizures is characterized by increased long-distance synchronization between structures that are critical in processing awareness, including thalamus (Th) and parietal cortices. The degree of LOC was found to correlate with the amount of synchronization in thalamo-cortical systems. We suggest that excessive synchronization overloads the structures involved in consciousness processing, preventing them from treating incoming information, thus resulting in LOC.

Pressor effects on blood pressure induced by isovolumic bladder distension and electro-acupuncture stimulations in anesthetized rats.

The pressor effects on blood pressure (BP) elicited by electro-acupuncture (Ea) stimulations and vesico-vascular reflex (VVR) were investigated in anesthetized rats. Twenty adult female Sprague-Dawley rats were used throughout this study. Two acupoints, the Hoku (Li-4) and the Tsusanli (St-36), were tested by a low frequency Ea (LFEa, 2 Hz) and a high frequency Ea (HFEa, 20 Hz) with intensities 20 times that of the motor threshold. Ea at Tsusanli elicited no pressor effects (98.15 +/- 4.10% and 101.43 +/- 3.96% of pre-stimulation control in LFEa and HFEa, respectively) whereas pressor effects could be induced by Ea stimulations at Hoku (126.3 +/- 3.3% and 136.3 +/- 3.8% of pre-stimulation control in LFEa and HFEa, respectively, P < 0.01, n=10). In addition, the patterns of pressor effects elicited by LFEa and HFEa at Hoku were different, i.e., LFEa at Hoku elicited a tonic pressor effect, while HFEa elicited a phasic one. The VVR induced by bladder isovolumic saline distension also elicited a pressor effect on BP (119.2 +/- 2.2%, P < 0.01, n=10) in the same preparations during bladder contractions. The VVR did not modify the Ea-induced pressor responses, and vice versa, when both of them were superimposed. All the results suggested that the pressor effects elicited by the VVR and the Ea stimulation were additive responses. In addition, for future clinical application, our findings may imply that patients should be carefully monitored for signs and symptoms of autonomic dysfunction during clinical acupuncture treatments.

Comparison of bispectral index and composite auditory evoked potential index for monitoring depth of hypnosis in children.

BACKGROUND: In pediatric patients, the Bispectral Index (BIS), derived from the electroencephalogram, and the composite A-Line autoregressive index (cAAI), derived from auditory evoked potentials and the electroencephalogram, have been used as measurements of depth of hypnosis during anesthesia. The performance and reliability of BIS and cAAI in distinguishing different hypnotic states in children, as evaluated with the University of Michigan Sedation Scale, were compared. METHODS: Thirty-nine children (aged 2-16 yr) scheduled to undergo elective inguinal hernia surgery were studied. For all patients, standardized anesthesia was used. Prediction probabilities of BIS and cAAI versus the University of Michigan Sedation Scale and sensitivity/specificity were calculated. RESULTS: Prediction probabilities for BIS and cAAI during induction were 0.84 for both and during emergence were 0.75 and 0.74, respectively. At loss of consciousness, the median BIS remained unaltered (94 to 90; not significant), whereas cAAI values decreased (60 to 43; P < 0.001). During emergence, median BIS and cAAI increased from 51 to 74 (P < 0.003) and from 46 to 58 (P < 0.001), respectively. With respect to indicate consciousness or unconsciousness, 100% sensitivity was reached at cutoff values of 17 for BIS and 12 for cAAI. One hundred percent specificity was associated with a BIS of 71 and a cAAI of 60. To ascertain consciousness, BIS values greater than 78 and cAAI values above 52 were required. CONCLUSIONS: BIS and cAAI were comparable indicators of depth of hypnosis in children. Both indices, however, showed considerable overlap for different clinical conditions.

Effects of pain stimulation on bispectral index, heart rate and blood pressure at different minimal alveolar concentration values of sevoflurane.

BACKGROUND: The aim of the present study was to examine the level of unconsciousness measured with bispectral index (BIS) at different minimal alveolar concentration (MAC) levels of sevoflurane, and to study the hemodynamic and BIS reactions during noxious stimulation with transcutaneous electrical nerve stimulation (TENS) and an ice water pain test (IWP). METHODS: This study was approved by the Ethics Committee and was performed on 10 healthy, young volunteers (six males and four females), ASA physical status I. Anesthesia was induced and maintained with sevoflurane in an oxygen/air mixture. The volunteers were spontaneously breathing, but if necessary, ventilation was mechanically supported. TENS and IWP were performed at 1.0, 1.5 and 2.0 MAC of sevoflurane. RESULTS: At 1.0 MAC, there was a significant increase in BIS during pain stimulation both with IWP (P<0.03) and with TENS (P<0.005), but at 1.5 MAC there were no changes. A marked variation in BIS was seen at 2.0 MAC, with periods of burst suppression and periods of high BIS values despite clinical signs of deep anesthesia. These marked variations in BIS were seen before, during and after pain stimulation. One volunteer (# 8) had a short episode of convulsions at 2.0 MAC. CONCLUSION: BIS, heart rate and blood pressure increased during pain stimulation at 1.0 MAC but not at 1.5 MAC of sevoflurane. There was a remarkable variation in BIS at 2.0 MAC of sevoflurane, with BIS values indicating wakefulness despite clinical signs of deep anesthesia. This BIS variation is probably caused by epileptogenic activity due to sevoflurane.

Cerebellar tumour presenting with pathological laughter and gelastic syncope.

There is no report of patients in whom pathological laughter, a rare condition characterized by uncontrollable episodes of laughter usually triggered by unrelated stimuli, was ever closely associated with a loss of consciousness overtly linked with the onset of such uncontrollable laughter, also referred to as a gelastic syncope. A 53-year-old man presented with a 4-month history of syncope following intense and uncoordinated laughter. Physical and neurological examination was normal and the patient had no other typical cerebellar signs. We found a mass in the cerebellar vermis abutting the floor of the fourth ventricle, which upon histological examination after surgery proved to be an ependymoma. We emphasize that pathological laughter and gelastic syncope could represent unique and sole features of a cerebellar disorder.