Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.

Arterial to jugular-bulb lactate difference in patients undergoing elective brain tumor craniotomy.

Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular-bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular-bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed-effects model with jugular-bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular-bulb concentrations. The slope of the regression line between arterial and jugular-bulb lactate was 0.95 (95% CI 0.93-0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57-5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor-craniotomy patients probably does not originate from the brain.

Hyperlactatemia associated with elective tumor craniotomy: Protocol for an observational study of pathophysiology and clinical implications.

Hyperlactatemia occurs frequently after brain tumor surgery. Existing studies are scarce and predominantly retrospective, reporting inconsistent associations to new neurological deficits and prolonged hospital stay. Here we describe a protocol for a prospective observational study of hyperlactatemia during and after elective tumor craniotomy and the association with postoperative outcome, as well as selected pathophysiological aspects, and possible risk factors. We will include 450 brain tumor patients scheduled for elective craniotomy. Arterial blood samples for lactate and glucose measurement will be withdrawn hourly during surgery and until six hours postoperatively. To further explore the association of hyperlactatemia with perioperative insulin resistance, additional blood sampling measuring markers of insulin resistance will be done in 100 patients. Furthermore, in a subgroup of 20 patients, blood from a jugular bulb catheter will be drawn simultaneously with blood from the radial artery to measure the arterial to jugular venous concentration difference of lactate, in order to study the direction of cerebrovascular lactate flux. Functional clinical outcome will be determined by the modified Rankin Scale, length of stay and mortality at 30 days, 6 months, 1 year and 5 years. Clinical outcome will be compared between patients with and without hyperlactatemia. Multivariate logistic regression will be used to identify risk factors for hyperlactatemia. A statistical analysis plan will be publicized to support transparency and reproducibility. Results will be published in a peer-reviewed journal and presented at international conferences.

Fabrication of artificial opals by electric-field-assisted vertical deposition.

We present a new technique for large-scale fabrication of colloidal crystals with controllable quality and thickness. The method is based on vertical deposition in the presence of a DC electric field normal to the conducting substrate. The crystal structure and quality are quantitatively characterized by microradian X-ray diffraction, scanning electron microscopy, and optical reflectometry. Attraction between the charged colloidal spheres and the substrate promotes growth of thicker crystalline films, while the best-quality crystals are formed in the presence of repulsion. Highly ordered thick crystalline layers with a small amount of stacking faults and a low mosaic spread can be obtained by optimizing the growth conditions.

[Use of capnography in the emergency department].

In Denmark, capnography is routinely used in monitoring patients with artificial airways. Non-invasive capnography is occasionally used by prehospital providers, but not applied inside hospital walls. Multiple studies illustrate benefits from capnography in non-intubated patients. Non-invasive capnography may reveal altered ventilation in conditions such as opioid-induced respiratory depression and acute dyspnoea, during metabolic acidosis and among patients with seizures and cerebral damage. Implementation requires education, guidelines for inhospital use and financial investment.

Automated pupillometry to detect command following in neurological patients: a proof-of-concept study.

BACKGROUND: Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in clinically unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis. METHODS: To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including seven patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic. RESULTS: Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of five arithmetic tasks. None of the five sedated and unconscious ICU patients passed this threshold. CONCLUSIONS: Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal covert consciousness in unresponsive patients in whom standard investigations have failed to detect signs of consciousness.