Search

Deep brain stimulation (DBS) for Parkinson’s disease (PD) often necessitates frequent clinic visits for stimulation program optimization, with limited experience in remote patient management. Due to the resource-intensive nature of these procedures, we investigated a way to simplify stimulation optimization for these patients that allows for the continuous monitoring of symptoms while also reducing patient burden and travel distances. To this end, we prospectively recruited ten patients treated with DBS for PD to evaluate the feasibility of telemedicinal optimization in a home-based setting. Patients recorded daily videos of a modified Unified Parkinson’s Disease Rating Scale (UPDRS) III, which experienced DBS physicians located at the clinic assessed to provide instructions on adjusting stimulation settings using a handheld programmer with previously set programs as well as patient amplitude control. This study concluded with significant improvements in participants’ motor status as measured by the UPDRS-III (p = 0.0313) compared to baseline values. These findings suggest that remote video-guided optimization of DBS settings is feasible and may enhance motor outcomes for patients.

The locus coeruleus–norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation.

Background The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. We compared clinical and technical outcomes with first‐line stent retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international case–control study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion presenting within 24 hours of time last seen well from January 2015 to August 2022. The primary outcome was the first‐pass effect (FPE), defined as expanded Treatment in Cerebral Infarction (TICI) 2c/3 on the first pass. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. Results There were 326 patients who met inclusion criteria, 56.1% male, median age 75 (interquartile range 65–82) years, and median National Institutes of Health Stroke Scale score 8 (5–12). Occlusion segments were PCA‐P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. FPE was lower in patients treated with first‐line CA or combined technique compared with SR (CA versus SR: adjusted odds ratio 0.45 [0.19–1.06]; P=0.07; combined versus SR: adjusted odds ratio 0.35 [0.016–0.80]; P=0.01). There were lower odds of functional independence (modified Rankin scale score 0–2) in the first‐line CA versus SR alone group (adjusted odds ratio 0.52 [0.28–0.95]; P=0.04). FPE was associated with higher rates of favorable outcomes (modified Rankin scale score 0–2: 58% versus 43.4%; P=0.01; modified Rankin scale score 0–1: 36.6% versus 25.8%; P=0.05). Overall, symptomatic intracranial hemorrhage was present in 5.6% (18/326) and mortality in 10.9% (35/326) without difference between first‐line technique. Conclusion In patients with isolated PCA occlusion, SR was associated with a higher rate of FPE compared with CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90 days was more likely with first‐line SR compared with CA. FPE was associated with better 90‐day clinical outcomes.

Abstract Objective Retinoic acid (RA) is known to transition proliferating SH-SY5Y neuroblastoma cells towards functional neurons. However, the activity of RA is restricted due to its photolability where any findings from prolonged time course observations using microscopy may alter outcomes. The aim of the study was to establish a real-time, long-term (9-day) protocol for the screening of differentiation events using Electrical cell-substrate impedance sensing (ECIS). Results and discussion A differentiation baseline for SH-SY5Y cells was established. Cells were seeded and exposed to repeated spikes of RA using the xCELLigence real-time cell analyser single plate (RTCA-SP) for real-time monitoring and identification of differentiation activity over a 9 day period in order to be more representative of differentiation over a prolonged timeline. Specific features associated with differentiation (growth inhibition, neurite outgrowths) were confirmed by end-point analysis. RA-induced growth inhibition and assumed phenotypic changes (i.e. neurite outgrowth) were identified by the xCELLigence analysis and further confirmed by end-point metabolic and phenotypic assays. Change in cellular morphology and neurite outgrowth length was identified by end-point fluorescence detection followed by computational analysis. Based on this it was possible to identify SH-SY5Y phenotypic differentiation with distinct phases observed over 9 days using Electric cell-substrate impedance sensing (ECIS) cell index traces providing a path to application in larger scale neurotrophic factor screening using this scalable technology.

Abstract Objective In Alzheimer's disease (AD), the presence of circadian dysfunction is well‐known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. Methods We included 29 mild–moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest‐activity rhythm, chromatic pupillometry analyzed with a new data‐fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. Results We demonstrated a significant thinning of the infero‐temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian‐impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil‐light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. Interpretation Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Light use is rising steeply, mainly because of the advent of light-emitting diode (LED) devices. LEDs are frequently blue-enriched light sources and may have different impacts on the non-image forming (NIF) system, which is maximally sensitive to blue-wavelength light. Most importantly, the timing of LED device use is widespread, leading to novel light exposure patterns on the NIF system. The goal of this narrative review is to discuss the multiple aspects that we think should be accounted for when attempting to predict how this situation will affect the NIF impact of light on brain functions. We first cover both the image-forming and NIF pathways of the brain. We then detail our current understanding of the impact of light on human cognition, sleep, alertness, and mood. Finally, we discuss questions concerning the adoption of LED lighting and screens, which offer new opportunities to improve well-being, but also raise concerns about increasing light exposure, which may be detrimental to health, particularly in the evening.

Introduction The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06], p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8

BACKGROUND The locus coeruleus (LC) is the primary source of norepinephrine in the brain and regulates arousal and sleep. Animal research shows that it plays important roles in the transition between sleep and wakefulness, and between slow wave sleep and rapid eye movement sleep (REMS). It is unclear, however, whether the activity of the LC predicts sleep variability in humans.METHODS We used 7-Tesla functional MRI, sleep electroencephalography (EEG), and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 33 healthy younger (~22 years old; 28 women, 5 men) and 19 older (~61 years old; 14 women, 5 men) individuals.RESULTS We found that, in older but not in younger participants, higher LC activity, as probed during an auditory attentional task, was associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS. The results remained robust even when accounting for the age-related changes in the integrity of the LC.CONCLUSION These findings suggest that LC activity correlates with the perception of the sleep quality and an essential oscillatory mode of REMS, and we found that the LC may be an important target in the treatment of sleep- and age-related diseases.FUNDING This work was supported by Fonds National de la Recherche Scientifique (FRS-FNRS, T.0242.19 & J. 0222.20), Action de Recherche Concertée – Fédération Wallonie-Bruxelles (ARC SLEEPDEM 17/27-09), Fondation Recherche Alzheimer (SAO-FRA 2019/0025), ULiège, and European Regional Development Fund (Radiomed & Biomed-Hub).

A case of a man with the recent onset of painful bilateral firm gynecomastia is reported. Mammography confirmed increased breast density. Biopsy characterized both masses as metastases of a small-cell lung tumor. This case highlights the atypical presentation and complements the literature regarding the rarity of breast metastases from small-cell lung cancer in men. Teaching point: Bilateral gynecomastia in a man with a long history of cigarette smoking should be considered with caution.