Refine
Document Type
- Article (7)
Has Fulltext
- yes (7)
Is part of the Bibliography
- no (7)
Keywords
- Brain activity (1)
- CHEPs (1)
- Capsaicin (1)
- Death (1)
- EEG reference choices (1)
- Electroencephalography (1)
- End-of-life (1)
- FOOOF (1)
- Rheumatoid arthritis (1)
- Unresponsive coma (1)
Institute
Highlights
• During the dying process, surges of higher-frequency activation can be seen in patients with unresponsive coma, raising concerns about possible conscious mental states.
• Parameterization of the power spectrum shows fundamental temporal changes during the last hour of dying.
• In the last minutes before death, parameterized neural activity is still fundamentally unique.
Abstract
Background: Cortical high-frequency activation immediately before death has been reported, raising questions about an enhanced conscious state at this critical time. Here, we analyzed an electroencephalogram (EEG) from a comatose patient during the dying process with a standard bedside monitor and spectral parameterization techniques.
Methods: We report neurophysiologic features of a dying patient without major cortical injury. Sixty minutes of frontal EEG activity was recorded using the Sedline™ monitor. Quantitative metrics of the frequency spectrum, the non-oscillatory 1/f characteristic, and signal complexity with Lemple-Ziv-Welch and permutation entropy were calculated. In addition to comparing the EEG trajectories over time, we provide a comparison to EEG records obtained from other studies with well-known vigilance states (sleep, anesthesia, and wake).
Results: Although we observed changes in high-frequency activation during the dying process, larger alterations of the aperiodic EEG components were also noted. These changes differed dramatically when compared to EEG records representative of wake, slow-wave sleep, or anesthesia. Although still fundamentally unique, the neuronal activity present in the dying brain is more similar to REM sleep than any other state we tested.
Conclusion: Even in patients with coma, temporal dynamics in quantitative EEG features (including the aperiodic components) can be observed in the final hour before death.
Persistent and, in particular, neuropathic pain is a major healthcare problem with still insufficient pharmacological treatment options. This triggered research activities aimed at finding analgesics with a novel mechanism of action. Results of these efforts will need to pass through the phases of drug development, in which experimental human pain models are established components e.g. implemented as chemical hyperalgesia induced by capsaicin. We aimed at ranking the various readouts of a human capsaicin–based pain model with respect to the most relevant information about the effects of a potential reference analgesic. In a placebo‐controlled, randomized cross‐over study, seven different pain‐related readouts were acquired in 16 healthy individuals before and after oral administration of 300 mg pregabalin. The sizes of the effect on pain induced by intradermal injection of capsaicin were quantified by calculating Cohen's d. While in four of the seven pain‐related parameters, pregabalin provided a small effect judged by values of Cohen's d exceeding 0.2, an item categorization technique implemented as computed ABC analysis identified the pain intensities in the area of secondary hyperalgesia and of allodynia as the most suitable parameters to quantify the analgesic effects of pregabalin. Results of this study provide further support for the ability of the intradermal capsaicin pain model to show analgesic effects of pregabalin. Results can serve as a basis for the designs of studies where the inclusion of this particular pain model and pregabalin is planned.
Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.
The sedation management of patients with severe COVID-19 is challenging. Processed electroencephalography (pEEG) has already been used for sedation management before COVID-19 in critical care, but its applicability in COVID-19 has not yet been investigated. We performed this prospective observational study to evaluate whether the patient sedation index (PSI) obtained via pEEG may adequately reflect sedation in ventilated COVID-19 patients. Statistical analysis was performed by linear regression analysis with mixed effects. We included data from 49 consecutive patients. None of the patients received neuromuscular blocking agents by the time of the measurement. The mean value of the PSI was 20 (±23). The suppression rate was determined to be 14% (±24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of −3 to −4 (correlation expected PSI 25–50) in bedside examination was noted in 79.4% of the recordings. Linear regression analysis revealed a significant correlation between the sedative dosages of propofol, midazolam, clonidine, and sufentanil (p < 0.01) and the sedation index. Our results showed a distinct discrepancy between the RASS and the determined PSI. However, it remains unclear to what extent any discrepancy is due to the electrophysiological effects of neuroinflammation in terms of pEEG alteration, to the misinterpretation of spinal or vegetative reflexes during bedside evaluation, or to other causes.
Background: Transient receptor potential cation channel subfamily V member 1 (TRPV1) are sensitive to heat, capsaicin, pungent chemicals and other noxious stimuli. They play important roles in the pain pathway where in concert with proinflammatory factors such as leukotrienes they mediate sensitization and hyperalgesia. TRPV1 is the target of several novel analgesics drugs under development and therefore, TRPV1 genetic variants might represent promising candidates for pharmacogenetic modulators of drug effects.
Methods: A next-generation sequencing (NGS) panel was created for the human TRPV1 gene and in addition, for the leukotriene receptors BLT1 and BLT2 recently described to modulate TRPV1 mediated sensitisation processes rendering the coding genes LTB4R and LTB4R2 important co-players in pharmacogenetic approaches involving TRPV1. The NGS workflow was based on a custom AmpliSeq™ panel and designed for sequencing of human genes on an Ion PGM™ Sequencer. A cohort of 80 healthy subjects of Western European descent was screened to evaluate and validate the detection of exomic sequences of the coding genes with 25 base pair exon padding.
Results: The amplicons covered approximately 97% of the target sequence. A median of 2.81 x 10 6 reads per run was obtained. This identified approximately 140 chromosome loci where nucleotides deviated from the reference sequence GRCh37 hg19 comprising the three genes TRPV1, LTB4R and LTB4R2. Correspondence between NGS and Sanger derived nucleotide sequences was 100%.
Conclusions: Results suggested that the NGS approach based on AmpliSeq™ libraries and Ion Personal Genome Machine (PGM) sequencing is a highly efficient mutation detection method. It is suitable for large-scale sequencing of TRPV1 and functionally related genes. The method adds a large amount of genetic information as a basis for complete analysis of TRPV1 ion channel genetics and its functional consequences.
Akzidentielle Injektion eines unbekannten Notfallantidots zur Acetylcholinesteraseaktivierung
(2021)
Background and objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).
Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.