M.J.A.M. van Putten

Dynamic indices do not predict volume responsiveness in routine clinical practice

BACKGROUND Dynamic indices, including pulse pressure, systolic pressure, and stroke volume variation (PPV, SPV, and SVV), are accurate predictors of fluid responsiveness under strict conditions, for example, controlled mechanical ventilation using conventional tidal volumes (TVs) in the absence of cardiac arrhythmias. However, in routine clinical practice, these prerequisites are not always met. We evaluated the effect of regularly used ventilator settings, different calculation methods, and the presence of cardiac arrhythmias on the ability of dynamic indices to predict fluid responsiveness in sedated, mechanically ventilated patients. METHODS We prospectively evaluated 47 fluid challenges in 29 consecutive cardiac surgery patients. Patients were divided into different groups based on TV. Dynamic indices were calculated in various ways: calculation over 30 s, breath-by-breath (with and without excluding arrhythmias), and with correction for TV. RESULTS The predictive value was optimal in the group ventilated with TVs >7 ml kg(-1) with correction for TV, calculated breath-by-breath, and with exclusion of arrhythmias [area under the curve (AUC)=0.95, 0.93, and 0.90 for PPV, SPV, and SVV, respectively]. Including patients ventilated with lower TVs decreased the predictive value of all dynamic indices, while calculating dynamic indices over 30 s and not excluding cardiac arrhythmias further reduced the AUC to 0.51, 0.63, and 0.51 for PPV, SPV, and SVV, respectively. CONCLUSIONS PPV, SPV, and SVV are the only reliable predictors of fluid responsiveness under strict conditions. In routine clinical practice, factors including low TV, cardiac arrhythmias, and the calculation method can substantially reduce their predictive value.

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery

OBJECTIVE Removal of brain tissue showing high frequency oscillations (HFOs; ripples: 80-250Hz and fast ripples: 250-500Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG). METHODS HFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes. RESULTS Ripple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p=0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex. CONCLUSIONS Our observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex. SIGNIFICANCE Fast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.

Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions*

Objective:Mechanical ventilation causes cyclic changes in the heart’s preload and afterload, thereby influencing the circulation. However, our understanding of the exact physiology of this cardiopulmonary interaction is limited. We aimed to thoroughly determine airway pressure distribution, how this is influenced by tidal volume and chest compliance, and its interaction with the circulation in humans during mechanical ventilation. Design:Intervention study. Setting:ICU of a university hospital. Patients:Twenty mechanically ventilated patients following coronary artery bypass grafting surgery. Intervention:Patients were monitored during controlled mechanical ventilation at tidal volumes of 4, 6, 8, and 10 mL/kg with normal and decreased chest compliance (by elastic binding of the thorax). Measurements and Main Results:Central venous pressure, airway pressure, pericardial pressure, and pleural pressure; pulse pressure variations, systolic pressure variations, and stroke volume variations; and cardiac output were obtained during controlled mechanical ventilation at tidal volume of 4, 6, 8, and 10 mL/kg with normal and decreased chest compliance. With increasing tidal volume (4, 6, 8, and 10 mL/kg), the change in intrathoracic pressures increased linearly with 0.9 ± 0.2, 0.5 ± 0.3, 0.3 ± 0.1, and 0.3 ± 0.1 mm Hg/mL/kg for airway pressure, pleural pressure, pericardial pressure, and central venous pressure, respectively. At 8 mL/kg, a decrease in chest compliance (from 0.12 ± 0.07 to 0.09 ± 0.03 L/cm H2O) resulted in an increase in change in airway pressure, change in pleural pressure, change in pericardial pressure, and change in central venous pressure of 1.1 ± 0.7, 1.1 ± 0.8, 0.7 ± 0.4, and 0.8 ± 0.4 mm Hg, respectively. Furthermore, increased tidal volume and decreased chest compliance decreased stroke volume and increased arterial pressure variations. Transmural pressure of the superior vena cava decreased during inspiration, whereas the transmural pressure of the right atrium did not change. Conclusions:Increased tidal volume and decreased chest wall compliance both increase the change in intrathoracic pressures and the value of the dynamic indices during mechanical ventilation. Additionally, the transmural pressure of the vena cava is decreased, whereas the transmural pressure of the right atrium is not changed.

EEG in postanoxic coma: Prognostic and diagnostic value

Evolution of the EEG background pattern is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest. At 24h, persistent isoelectricity, low voltage activity, or burst-suppression with identical bursts predicts a poor outcome without false positives. Rapid recovery toward continuous patterns within 12h is strongly associated with a good neurological outcome. Predictive values are highest in the first 24h, despite the use of mild therapeutic hypothermia and sedative medication. Studies on reactivity or mismatch negativity have not included the EEG background pattern. Therefore, the additional predictive value of reactivity parameters remains unclear. Whether or not treatment of electrographic status epilepticus improves outcome is studied in the randomized multicenter Treatment of Electroencephalographic STatus epilepticus After cardiopulmonary Resuscitation (TELSTAR) trial (NCT02056236).

Predicting success of vagus nerve stimulation (VNS) from interictal EEG

PURPOSE Vagus nerve stimulation (VNS) has shown to be an effective treatment for drug resistant epilepsy in numerous patients, however, not in all. It is still not possible to predict which patients will profit from VNS. In this pilot study, we explore predictive interictal EEG features for seizure reduction after VNS. METHODS 19 Patients with medically refractory epilepsy and an implanted VNS system were included. Interictal EEG registrations, recorded before implantation, were retrospectively analysed. A quantative symmetry measure, the pair wise derived brain symmetry index (pdBSI), was tested to predict VNS outcome. Reduction in seizure frequency was used to define the responders. RESULTS 10 Patients did respond to VNS, of whom 7 patients had a seizure reduction of at least 50% in a follow-up period of 2 years. On average, we find higher pdBSI values for delta, theta, alpha and beta bands for non-responders than for responders. The average pdBSI of the theta and alpha bands could significantly discriminate between responders and non-responders. CONCLUSION In this study, quantifying EEG symmetry using the pdBSI shows promising results in predicting the reduction of seizure frequency after VNS treatment.

Single Pulse Electrical Stimulation to identify epileptogenic cortex : Clinical information obtained from early evoked responses

OBJECTIVE Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). RESULTS Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

Event-related mu-rhythm desynchronization during movement observation is impaired in Parkinson’s disease

OBJECTIVE Patients with Parkinsons disease often experience difficulties in adapting movements and learning alternative movements to compensate for symptoms. Since observation of movement has been demonstrated to lead to the formation of a lasting specific motor memory that resembled that elicited by physical training we hypothesize that mu-rhythm desynchronization in response to movement observation is impaired in Parkinsons disease. METHOD In a pilot study with nine patients with Parkinsons disease at a Hoehn and Yahr stage of I or II and eleven age-matched controls, we tested this hypothesis by comparing the event related desynchronization (ERD) patterns from the EEG recorded during the observation of hand action and baseline videos. RESULTS Healthy subjects showed normal bilateral ERD of the mu-rhythm. In patients with Parkinsons disease this distinct ERD pattern was lacking. CONCLUSION The results of this study suggest that event-related mu-rhythm desynchronization is impaired in Parkinsons disease, even at early stages of the disease. SIGNIFICANCE Studying event-related mu-rhythm desynchronization dysfunction in Parkinsons disease patients may enhance our understanding of symptoms as impaired motor learning.

Microneedle array electrode for human EEG recording

Microneedle array electrodes for EEG significantly reduce the mounting time, particularly by circumvention of the need for skin preparation by scrubbing. We designed a new replication process for numerous types of microneedle arrays. Here, polymer microneedle array electrodes with 64 microneedles, in a nested 4×4 array, positioned on a circular disk of 10 mm diameter were fabricated and characterized. Needles have a length of 320 μm with a diameter of 100 μm. The DC-resistance of Ag-coated microneedle array electrodes on the skin is of the order of 150 kΩ. Using electrolyte gel this value decreases at least by a factor of 10. The pilot measurements on a healthy volunteer show excellent signal-to-noise ratios. According to conventional electrodes also Ag/AgCl instead of Ag only was used to coat the microneedle array. Both coatings, either with or without gel, certified for EEG recordings

Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study

OBJECTIVE In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities. METHODS We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest. RESULTS The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses. CONCLUSIONS In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission. SIGNIFICANCE Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time.

Suppressors of interictal discharges in idiopathic childhood occipital epilepsy of Gastaut

Idiopathic childhood occipital epilepsy of Gastaut (ICOE-G) is a rare form of epilepsy, characterized by visual hallucinations, periods of blindness, motor seizures, and migraine-like symptoms. A characteristic EEG feature is fixation-off sensitivity: epileptiform discharges are suppressed by visual input. Here, we present an 11-year-old girl suffering from ICOE-G, who was studied to identify potential additional suppressors of the epileptiform discharges.