[Alopecia areata with good response to tofacitinib]. / Alopecia areata mit gutem Ansprechen auf Tofacitinib.

We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2â€¯× 5 mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.

Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study.

INTRODUCTION: The highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses. METHODS: One hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 µg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 µg ml-1; n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions. RESULTS: At the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRglu did not differ from placebo. CONCLUSIONS: At equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia. CLINICAL TRIAL REGISTRATION: NCT02624401.

Electroencephalogram reactivity to verbal command after dexmedetomidine, propofol and sevoflurane-induced unresponsiveness.

Although electroencephalogram reactivity (i.e. transient changes in electrical brain activity following external stimulus) might be useful in depth-of-anaesthesia monitoring, it has not been systematically examined with different anaesthetics at doses titrated to unresponsiveness. Three 10-subject groups of healthy volunteers received dexmedetomidine, propofol or sevoflurane in escalating pseudo-steady-state concentrations at 10-min intervals until they did not open their eyes to command. The electroencephalogram was continuously recorded and spectral variables were calculated with short-time Fourier transform and time-varying autoregressive modelling. Electroencephalogram reactivity was most prominent in the midfrontal derivations (termed F3 and F4). During drug-induced unresponsiveness, electroencephalogram reactivity was still present in all drug groups. Dexmedetomidine, propofol and sevoflurane induced distinct suppression patterns on the electroencephalogram reactivity at the same clinical endpoint (unresponsiveness). Reactivity was best maintained with propofol, while only minimally preserved with dexmedetomidine and sevoflurane. Thus, it may be difficult to harness reactivity for depth-of-anaesthesia monitoring.

Wide inter-individual variability of bispectral index and spectral entropy at loss of consciousness during increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

BACKGROUND: The bispectral index (BIS) and the spectral entropy (state entropy, SE, and response entropy, RE) are depth-of-anaesthesia monitors derived from EEG and have been developed to measure the effects of anaesthetics on the cerebral cortex. We studied whether they can differentiate consciousness from unconsciousness during increasing doses of three different anaesthetic agents. METHODS: Thirty healthy male volunteers aged 19-30 yr were recruited and divided into three 10-volunteer groups to receive either dexmedetomidine, propofol, or sevoflurane in escalating concentrations at 10 min intervals until loss of consciousness (LOC) was reached. Consciousness was tested at 5 min intervals and after drug discontinuation at 1 min intervals by requesting the subjects to open their eyes. LOC was defined as unresponsiveness to the request and pre-LOC as the last meaningful response. The first meaningful response to the request after drug discontinuation was defined as regaining of consciousness (ROC). For the statistical analysis, pre-LOC and ROC values were pooled to represent the responsive state while LOC values represented the unresponsive state. Prediction probability (P(K)) was estimated with the jack-knife method. RESULTS: The lowest mean values for BIS, SE, and RE were recorded at LOC with all three drugs. The P(K) values were low for dexmedetomidine (BIS 0.62, SE 0.58, RE 0.59), propofol (BIS 0.73, SE 0.72, RE 0.72), and sevoflurane (BIS 0.70, SE 0.52, RE 0.62). CONCLUSIONS: Because of wide inter-individual variability, BIS and entropy were not able to reliably differentiate consciousness from unconsciousness during and after stepwise increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep.

BACKGROUND: Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, induces a unique, sleep-like state of sedation. The objective of the present work was to study human electroencephalogram (EEG) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep, to test the hypothesis that dexmedetomidine exerts its effects via normal sleep-promoting pathways. METHODS: EEG was continuously recorded from a bipolar frontopolar-laterofrontal derivation with Entropy Module (GE Healthcare) during light and deep dexmedetomidine sedation (target-controlled infusions set at 0.5 and 3.2 ng/ml) in 11 healthy subjects, and during physiological sleep in 10 healthy control subjects. Sleep spindles were visually scored and quantitatively analyzed for density, duration, amplitude (band-pass filtering) and frequency content (matching pursuit approach), and compared between the two groups. RESULTS: In visual analysis, EEG activity during dexmedetomidine sedation was similar to physiological stage 2 (S2) sleep with slight to moderate amount of slow-wave activity and abundant sleep spindle activity. In quantitative EEG analyses, sleep spindles were similar during dexmedetomidine sedation and normal sleep. No statistically significant differences were found in spindle density, amplitude or frequency content, but the spindles during dexmedetomidine sedation had longer duration (mean 1.11 s, SD 0.14 s) than spindles in normal sleep (mean 0.88 s, SD 0.14 s; P=0.0014). CONCLUSIONS: Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol. RESULTS: The entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18) and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual variation of entropy indices was wide and their specificity to indicate unconsciousness was poor. Propofol induced more pronounced increase in delta power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S-ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG power bands probably explain why entropy monitor, while adequate for propofol, is not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

Kalman smoother based time-varying spectrum estimation of EEG during single agent propofol anesthesia.

A time-varying parametric spectrum estimation method for analyzing EEG dynamics is presented. EEG signals are first modeled as a time-varying auto-regressive stochastic process and the model parameters are estimated recursively with a Kalman smoother algorithm. Time-varying spectrum estimates are then obtained from the estimated parameters. The proposed method was applied to measurements collected during low dose propofol anesthesia. The method was able to detect changes of event related (de)synchronization type elicited by verbal command.

Assessing the depth of dexmedetomidine-induced sedation with electroencephalogram (EEG)-based spectral entropy.

BACKGROUND: Adequate sedation of critically ill patients improves the outcome of intensive care. Maintaining an optimal level of sedation in the intensive care unit (ICU) is difficult because of a lack of appropriate monitoring methods to guide drug dosing. Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, has recently been introduced for the sedation of ICU patients. This study investigated the utility of electroencephalogram (EEG)-based spectral entropy monitoring (with M-ENTROPY, GE Healthcare, Helsinki, Finland) for the assessment of dexmedetomidine-induced sedation. METHODS: Eleven healthy, non-smoking men, aged 23.9 +/- 2.5 years (mean +/- standard deviation), were recruited. Spectral entropy was recorded before and during low (0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. At the end of the infusion, subjects were awakened by verbal command and light shaking. RESULTS: Spectral entropy decreased from 84 +/- 5 to 66 +/- 16 (P= 0.029) during low dexmedetomidine levels and from 84 +/- 5 to 20 +/- 12 (P < 0.001) during high dexmedetomidine levels. Transitions during loss and regaining of consciousness were analysed separately. Entropy decreased from 76 +/- 8 before to 43 +/- 10 (P < 0.001) after loss of consciousness, and increased from 14 +/- 4 to 63 +/- 13 (P < 0.001) on regaining of consciousness. These changes were consistent across all subjects. Prediction probability and sensitivity values indicated a high predictive performance of the method. CONCLUSION: The depth of dexmedetomidine-induced sedation can be monitored with EEG-based spectral entropy. These results should be confirmed in a clinical setting.

Correlation of EEG spectral entropy with regional cerebral blood flow during sevoflurane and propofol anaesthesia.

ENTROPY index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 microg.ml(-1) plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8-32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [(15)O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs.