Conscious and subconscious sensorimotor synchronization--prefrontal cortex and the influence of awareness.

One of the most compelling challenges for modern neuroscience is the influence of awareness on behavior. We studied prefrontal correlates of conscious and subconscious motor adjustments to changing auditory rhythms using regional cerebral blood flow measurements. At a subconscious level, movement adjustments were performed employing bilateral ventral mediofrontal cortex. Awareness of change without explicit knowledge of the nature of change led to additional ventral prefrontal and premotor but not dorsolateral prefrontal activations. Only fully conscious motor adaptations to a changing rhythmic pattern showed prominent involvement of anterior cingulate and dorsolateral prefrontal cortex. These results demonstrate that while ventral prefrontal areas may be engaged in motor adaptations performed subconsciously, only fully conscious motor control which includes motor planning will involve dorsolateral prefrontal cortex.     

Failure of Two Commercial Indexes and Spectral Parameters to Reflect the Pharmacodynamic Effect of Desflurane on EEG

Objective We compared two PK/PD models, one with and one without a plateau effect. Bispectral (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend™ (NCT, MonitorTechnik, Bad Bramstedt, Germany, Version 4.0) indices were used as an electroencephalographic measure of desflurane drug effect. Methods With IRB approval and informed consent we investigated 20 adult patients scheduled for radical prostatectomy. At least 45 minutes after induction of general anaesthesia, end-tidal concentrations of desflurane was varied between 3 and 10 vol%. To evaluate the relationship between concentrations and EEG indices, two different pharmacodynamic models were applied: A conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models␣were estimated by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. Results The maximum end-tidal desflurane concentration during the two concentrations ramps was 10.0 ± 1.4 vol%. The mean BIS and NCT values decreased significantly but slightly with increasing end-tidal desflurane concentrations between 4 and 8 vol%. Therefore a two sigmoidal curves PK/PD model including a plateau describes the effects of desflurane on BIS and Narcotrend better than a single sigmoidal curve model. The difference between the log likelihood values of the new PK/PD model with two connected sigmoidal curves and the classical E _max model with one sigmoidal curve is 634 (P < 0.001) for the BIS monitor and 4089 (P < 0.001) for the NCT. Conclusions BIS and Narcotrend are not useful to differentiate pharmacodynamic changes in the EEG between 4 and 9 vol% desflurane. This study was presented in part at the American Society of Anesthesiologists meeting October 20, 2005 Atlanta. Kreuer S, Bruhn J, Ellerkmann R, Ziegeler S, Kubulus D, Wilhelm W. Failure of two commercial indexes and spectral parameters to reflect the pharmacodynamic effect of desflurane on EEG.     

Comparison of patient‐reported outcome measures in multiple sclerosis

Background

Patient‐reported outcome measurements (PROMS) have been proposed sensitive outcome parameters in multiple sclerosis (MS). In this study, we assessed a German version of the Multiple Sclerosis Impact Scale (MSIS‐29) and a revised version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) in comparison with rater‐ and physician‐based tools.

Methods

Consecutive MS patients (n = 117) of the MS outpatient unit were included. In addition to MSIS‐29 and HAQUAMS, the following parameters were obtained: Expanded Disability Status Scale (EDSS) and modified Multiple Sclerosis Functional Composite (MSFC) [9‐hole peg test (9HPT), 25‐foot walk test and symbol digit modalities test]. We investigated validity, internal consistency and test–retest reliability as well as correlation between these measures.

Results

Internal consistency (Cronbach's α ≤ 0.96) and test–retest coefficients (ICC ≤ 0.87) of both scales were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlation with other rater‐based measures depending on the functional subdomain. Both MSIS‐29 and HAQUAMS correlated with EDSS (ρ = 0.55 vs 0.62), but stronger correlation was found between MSIS‐29 and HAQUAMS total score (ρ = 0.90). Both scales distinguished between patient groups of varied disease severity and cognitive impairment.

Conclusion

Patient‐reported outcome measurements as MSIS‐29 and HAQUAMS seem to be valid instruments to detect different impairment levels in comparison with traditional rater‐based instruments like EDSS or MSFC.     

Takotsubo Cardiomyopathy (Acute Left Ventricular Apical Ballooning Syndrome) Occurring in the Intensive Care Unit

Objective Diagnosis of Takotsubo cardiomyopathy (also known as stress cardiomyopathy or acute left ventricular apical ballooning syndrome) can be challenging in patients who are being treated for other diseases in the intensive care unit, because symptoms could erroneously be attributed to the underlying disease or patients may not experience symptoms due to analgesia and sedation. The aim of our study was to assess clinical features of Takotsubo cardiomyopathy occurring in the intensive care unit.Design Prospective observational study.Setting University hospital.Patients Six consecutive patients diagnosed with Takotsubo cardiomyopathy who were being treated for other diseases in the intensive care unit.Interventions None.Measurements and main results Sudden hemodynamic deterioration (i.e., sudden hypotension, tachycardia or drop in monitored stroke volume) requiring vasopressor support was the presenting symptom in five of the six patients. Only one patient was able to report angina-like chest pain, all others were unable to experience symptoms due to analgesia and sedation. The electrocardiogram was abnormal in all patients upon diagnosis, demonstrating either ST-segment elevation (n = 2) and/or T-wave inversion (n = 5). Mild elevation of cardiac enzymes disproportionate to the extent of wall motion abnormalities on left ventriculography was present in all patients. All patients survived their acute event.Conclusions Sudden hemodynamic deterioration requiring vasopressor support and/or ECG abnormalities consisting of ST-segment elevation, ST-segment depression or T-wave inversion may be the presenting symptom of Takotsubo cardiomyopathy in the intensive care unit and should be included in the diagnostic algorithm.This work was carried out without any financial support. The authors have no financial interest in this article.     

Pyrithioxine: a new basic treatment of rheumatoid arthritis. Open study of 60 cases with a follow-up of 6 months

Pyrithioxine, a chemical compound with several points in common with penicillinamine, was used for six months as the basic treatment in a series of 60 cases of rheumatoid arthritis, in a dose of 600 mg per day. The results were favourable in 60 per cent of cases, with a marked fall in articular index, a return to normal of sedimentation rate and, less commonly, negativisation of the Rose-Waaler reaction. Side effects were essentially cutaneo-mucosal (pruitus, rash) and necessitated the interruption of treatment in 16.5 per cent of cases. No complications were seen. Compared with penicillinamine, pyrithioxine appears to be less effective but better tolerated. The place of this new basic drug in the basic treatment of rheumatoid arthritis remains to be precisely determined.     

The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states.Subject terms: Predictive markers, Psychosis     

Establishment of Recombinant Trisegmented Mopeia Virus Expressing Two Reporter Genes for Screening of Mammarenavirus Inhibitors

Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens under biosafety level 4 conditions. These containment restrictions make large-scale screens of antiviral compounds difficult. Therefore, the Mopeia virus (MOPV), closely related to LASV, is often used as an apathogenic surrogate virus. We established for the first time trisegmented MOPVs (r3MOPV) with duplicated S segments, in which one of the viral genes was replaced by the reporter genes ZsGreen (ZsG) or Renilla Luciferase (Rluc), respectively. In vitro characterization of the two trisegmented viruses (r3MOPV ZsG/Rluc and r3MOPV Rluc/ZsG), showed comparable growth behavior to the wild type virus and the expression of the reporter genes correlated well with viral titer. We used the reporter viruses in a proof-of-principle in vitro study to evaluate the antiviral activity of two well characterized drugs. IC₅₀ values obtained by Rluc measurement were similar to those obtained by virus titers. ZsG expression was also suitable to evaluate antiviral effects. The trisegmented MOPVs described here provide a versatile and valuable basis for rapid high throughput screening of broadly reactive antiviral compounds against arenaviruses under BSL-2 conditions.