Cold allodynia, meaning that innocuous cold stimuli become painful, is a characteristic, but enigmatic feature of neuropathic pain. Here, we used functional magnetic resonance imaging (fMRI) and ...investigated brain activations underlying menthol-induced cold allodynia. 12 healthy volunteers were investigated using a block-design fMRI approach. Firstly, brain activity was measured during application of innocuous cold stimuli (at 5 °C above cold pain threshold) and noxious cold stimuli (at 5 °C below cold pain threshold) to normal skin of the forearm using a peltier- driven thermostimulator. The stimuli were adjusted to the individual cold pain threshold. Secondly, cold allodynia was induced by topical menthol and cortical activations were measured during previously innocuous cold stimulation (i.e. cold pain threshold +5 °C), that were then perceived as painful. On a numeric rating scale for pain (0–10) innocuous cold, cold pain and cold allodynia were rated to 0.9±0.3, 4.1±0.3 and 4.5±0.5, respectively. Sensory and affective components of allodynic and cold pain were equal in the McGill pain questionnaire. All tested conditions (innocuous cold, noxious cold and cold allodynia) led to significant activations of bilateral insular cortices, bilateral frontal cortices and the anterior cingulate cortex. When noxious cold and innocuous cold were compared, noxious cold contributed significantly more to activations of the posterior insula and innocuous cold contributed more to activations of ipsilateral anterior insular cortex. However, comparing cold allodynia and equally intense cold pain conditions, we found significantly increased activations in bilateral dorsolateral prefrontal cortices (DLPFC) and the brainstem (ipsilateral parabrachial nucleus) during cold allodynia. Furthermore, in contrast maps cold allodynia contributed significantly more to activations of the bilateral anterior insula, whereas the contribution to activation of the contralateral posterior insula was equal. It is concluded that cold allodynia activates a network similar to that of normal cold pain but additionally recruits bilateral DLPFC and the midbrain, suggesting that these brain areas are involved in central nociceptive sensitisation processes.
Background
The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) ...LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population.
Methods and Results
INTERMACS 1 LVAD recipients from five U.S. centers were included. In‐hospital and one‐year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non‐ECMO patients by propensity‐weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one‐year outcomes. One hundred and twenty‐seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 95%CI 1.06–9.77, p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non‐ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non‐ECMO: 4.9%, p = 0.006). Among the study cohort, one‐year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients.
Conclusions
Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one‐year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.
Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one‐year survival was seen com‐ pared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.
Acute ischaemic stroke in brain areas contributing to male sexual function may impair erectile function depending on the lesion site. This study intended to determine associations between ...stroke-related erectile dysfunction and cerebral ischaemic lesion sites using voxel-based lesion mapping. In 52 males (mean age 60.5 ± 10.5 years) with first-ever ischaemic strokes, we assessed erectile function after and retrospectively 3 months prior to the stroke using scores of the 5-item International Index of Erectile Function-5 questionnaire. We assessed cardiovascular risk factors and determined clinical stroke severity and infarct volumes as well as total brain volume by neuroimaging. We calculated correlations between patient age, clinical stroke severity, infarct volumes as well as brain volumes and the difference between erectile dysfunction scores before and after stroke. Moreover, we compared patient age, prevalence of cardiovascular risk factors, clinical stroke severity, infarct volumes and brain volumes of patients with unchanged and deteriorated erectile function after stroke. The infarcts were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed subtraction analyses of lesions. In a voxel-based lesion analysis, the difference between erectile dysfunction scores before and after stroke was correlated with the lesion site using t-test statistics. Finally, we conducted a region of interest-based multivariate linear regression analysis that was adjusted for potential confounding factors including patient age, clinical stroke severity, imaging modality, lesion size and brain volume. In 32 patients (61.5%) erectile dysfunction scores declined after the stroke and therefore had stroke-related erectile dysfunction. Deterioration of erectile dysfunction scores was not associated with patient age, clinical stroke severity, infarct volume, brain volume, and cardiovascular risk factors. The voxel-wise subtraction analysis showed associations between stroke-related erectile dysfunction and lesion sites in the right occipito-parietal cortex and thalamus, as well as in the left insula and adjacent temporo-parietal areas. Using voxel-wise t-test statistics, we showed associations between deterioration of erectile function and lesion sites in the right occipital and thalamic region, and the left parietal association area. The linear regression analysis showed that stroke-related erectile dysfunction remained associated with lesions of the right occipital and left parietal association areas after adjusting for confounding factors. In conclusion, our voxel-wise analysis indicates that deteriorating erectile function after stroke is associated with lesions in the right occipito-parietal and thalamic areas integrating visual and somatosensory information, as well as lesions in the left insular and adjacent parieto-temporal areas contributing to generating and mapping visceral arousal states.
Background Brain-derived neurotrophic factor (BDNF) signaling at synapses improves synaptic strengthening associated with learning and memory. In the present study we hypothesized that serum BDNF ...concentration is associated with in vivo level of cerebral N-acetylaspartate (NAA), a well established marker of neuronal integrity. Methods In 36 healthy subjects BDNF serum concentration and absolute concentration of NAA together with other metabolites were measured by proton magnetic resonance spectroscopy (1H-MRS) in regions with high BDNF levels (anterior cingulate cortex ACC, left hippocampus). Relationship between BDNF concentration and brain metabolites was studied in linear regression analysis with BDNF concentration as dependent variable and metabolite concentrations, age, and gender as predictor variables. Results The BDNF serum concentrations were positively associated with the concentrations of NAA (T = 2.193, p = .037) and total choline (T = 1.997, p = .055; trend) but not total creatine or glutamate in the ACC. No significant association was observed between BDNF serum concentration and absolute metabolite concentrations in the hippocampus. Conclusions The preliminary data might indicate that BDNF serum concentration reflects some aspects of neuronal plasticity as indicated by its association with NAA level in the cerebral cortex. The results would be in line with the notion that BDNF plays a central role in the regulation of neuronal survival and differentiation in the human brain.
Extracorporeal membrane oxygenation (ECMO) use in patients with cardiac arrest is increasing. Utilization remains variable between centers using ECMO as a rescue therapy or early protocolized ...extracorporeal cardiopulmonary resuscitation.
Single-center, retrospective evaluation of cardiac arrest with cardiopulmonary resuscitation and rescue ECMO support from 2011 through 2019. Study objectives included survival, non-neurologic, and neurologic outcomes; validation of the SAVE and modified SAVE (mSAVE) scores for survival and favorable neurologic outcome; and predictive factor identification in cardiac arrest with ECMO rescue therapy.
Eighty-nine patients were included. In-hospital survival was 38.2% and median CPC score was 2. Survivors had lower BMI (27.9 ± 4.2 kg/m2 vs. 32.3 ± 7.5 kg/m2, P = 0.003), less obesity (BMI ≥ 30 kg/m2) (26.5% vs. 49.1%, P = 0.035), shorter CPR duration (35.5 ± 31.7 m vs. 58.0 ± 49.5 m, P = 0.019), more tracheostomy (38.2% vs. 7.3%, P < 0.001), and less renal replacement therapy (RRT) (17.6% vs. 38.2%, P = 0.031). Patients with a favorable neurologic outcome had lower body weight (86.2 ± 17.9 kg vs. 98.1 ± 19.4 kg, P = 0.010), lower BMI (28.1 ± 4.5 kg/m2 vs. 33.9 ± 7.9 kg/m2, P < 0.001), and less obesity (29.7% vs. 56.3%, P = 0.026). mSAVE score predicted in-hospital survival (OR 1.11; 95%CI 1.03-1.19; P = 0.004) and favorable neurologic outcome (OR 1.11; 1.03-1.20; P = 0.009). Multivariate analysis for in-hospital survival included mSAVE, BMI, CPR-time, tracheostomy, and RRT (c-statistic: 0.864). Favorable neurologic outcome included mSAVE and BMI (c-statistic: 0.805).
mSAVE, BMI, RRT, and tracheostomy are predictors of in-hospital survival and mSAVE and BMI are predictors of favorable neurologic outcome in cardiac arrest with ECMO rescue therapy.
Growing evidence from animal studies indicates brain‐damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette ...smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never‐smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel‐based morphometry. Significantly smaller grey matter volume and lower grey matter density (P = 0.05, corrected) were observed in the frontal regions (anterior cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the temporal lobe including parahippocampal gyrus, in smokers than in never‐smokers. Group differences of either grey matter volume or grey matter density were also found in the thalamus, cerebellum and substantia nigra, among other regions. Smokers did not show greater volumes than never‐smokers in any cerebral region. Magnitude of lifetime exposure to tobacco smoke (pack‐years) was inversely correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001, uncorrected). The data indicate structural deficits of several cortical and subcortical regions in smokers relative to never‐smokers. The topographic profile of the group differences show some similarities to brain networks known to mediate drug reinforcement, attention and working memory processing. The present findings may explain in part the frequently reported cognitive dysfunctions in chronic cigarette consumers.
Recurrent bleeding events are a common complication of left ventricular assist devices leading to significant morbidity. Clinicians may be reluctant to discontinue all antithrombotic therapies in ...this setting because of the risk of thrombotic events. To evaluate the safety of this strategy, we conducted a retrospective review of patients within our institution’s left ventricular assist device program from February 2010 to July 2018 who had all antithrombotic therapies discontinued in response to recurrent bleeding events requiring hospitalization. Thrombotic and bleeding outcomes after discontinuation of therapy were assessed and compared. Seven patients out of 87 (8%) were identified and included in this analysis. One patient experienced pump thrombosis in the setting of driveline infection with an overall rate of thrombotic events of 0.08 per-patient-year. Sixteen gastrointestinal bleeding events occurred after discontinuation of antithrombotic therapy (1.35 per-patient-year) compared with 37 prior to discontinuation (4.28 per-patient-year) resulting in a significant reduction (reduction rate = 0.32; 95% confidence interval = 0.17, 0.58; p < .001). Thrombotic complications were rare among patients with HeartMate II left ventricular assist device support who suffered recurrent bleeding events and in whom antithrombotic therapy was, therefore, discontinued. Gastrointestinal bleeding was significantly reduced in this group; however, angioectasia-related gastrointestinal bleedings remained problematic.
Although pain is accompanied by autonomic nervous system responses, the cerebral circuits involved in the autonomic pain dimension remain elusive. Therefore, we used functional magnetic resonance ...imaging (fMRI) and investigated brain processing associated with cutaneous sympathetic vasoconstrictor reflexes during noxious stimulation. When a classical fMRI analysis based on the applied block design was performed, we were able to detect activations well known to be engaged in the central processing of touch and pain. A parametric fMRI analysis in which cutaneous vasoconstrictor activity was correlated with MRI signals revealed two distinct patterns of brain activity. During (i) noxious stimulation itself, brain activity correlated with sympathetic activity in the anterior insula, ventrolateral prefrontal cortex (VLPFC), anterior cingulate cortex (ACC), and secondary somatosensory cortex (S2). During (ii) baseline, brain activity correlated with sympathetic activity in the VMPFC, dorsolateral prefrontal cortex (DLPFC), OFC, PCC, cuneus, precuneus, occipital areas, and hypothalamus. Conjunction analysis revealed significant similar responses during periods of noxious stimulation and periods of sympathetic activation in the anterior insula, ACC and VLPFC (activation) and VMPFC, OFC, PCC, cuneus and precuneus (deactivation). Therefore, we here describe a cerebral network which may be engaged in the processing of the autonomic subdimension of the human pain experience.
► The cerebral circuits involved in the autonomic pain dimension remain unclear. ► The present fMRI study investigated cerebral sympathetic networks during pain. ► Sympathetic responses led to activity in prefrontal, insular and cingulate cortices. ► Therefore, a neural basis for the autonomic pain dimension is provided.
Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received ...epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.
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