Abstract Background Animal and human studies of Alzheimer’s disease (AD) demonstrated that aberrant network activity with neuronal hyperexcitability plays a role in disease pathogenesis and cognitive functioning. Suppressing network hyperexcitability with levetiracetam improved cognitive functioning in familial AD mice and executive functioning in patients with AD and epileptiform activity. Manifestations of network hyperexcitability are unsensitive biomarkers since they are mostly subclinical and not visible on scalp EEG. (Lam et al. 2019, Vossel et al. 2021, Sanchez et al. 2012) . Our purpose was to identify subclinical epileptiform activity in two patients with mild cognitive impairment (MCI) and one patient with moderate AD, with a suspicion of network hyperexcitability based on either spikes on 24‐h scalp EEG or a history suspect for seizures without epileptiform discharges on scalp EEG. Method Three patients were implanted with bilateral foramen ovale (FO) electrodes to obtain more direct measures of mesial temporal lobe epileptiform activity. Scalp EEG according to the 10‐20 system and polysomnography were simultaneously recorded in all subjects for three to five consecutive days. Polysomnography was scored according to the AASM scoring rules. Persyst 14 software was used for automatic spike detection. Result Invasive recordings showed interictal epileptic activity in all three patients, which was occasional during wakefulness and abundant during sleep. In one patient two nocturnal unilateral mesiotemporal seizures, characterized by arousal, were recorded during N1 sleep, while at the same time no epileptiform activity was visible on scalp EEG. Conclusion In patients with AD subclinical mesial temporal epileptiform activity can be present with a normal scalp EEG. Epileptic activity is predominantly found during sleep. Our findings suggest an important role for network hyperexcitability in AD disease pathogenesis.
The cortical network controlling the arm and hand when grasping objects consists of several areas in parietal and frontal cortex. Recently, more anterior prefrontal areas have also been implicated in object grasping, but their exact role is currently unclear. To investigate the neuronal encoding of objects during grasping in these prefrontal regions and their relation with other cortical areas of the grasping network, we performed large-scale recordings (more than 2000 responsive sites) in frontal cortex of monkeys during a saccade-reach-grasp task. When an object appeared in peripheral vision, the first burst of activity emerged in prearcuate areas (the FEF and area 45B), followed by dorsal and ventral premotor cortex, and a buildup of activity in primary motor cortex. After the saccade, prearcuate activity remained elevated while primary motor and premotor activity rose in anticipation of the upcoming arm and hand movement. Remarkably, a large number of premotor and prearcuate sites responded when the object appeared in peripheral vision and remained active when the object came into foveal vision. Thus, prearcuate and premotor areas continuously encode object information when directing gaze and grasping objects.
The human amygdala is considered a key region for successful emotion recognition. We recently reported that temporal lobe surgery (TLS), including resection of the amygdala, does not affect emotion recognition performance (Journal of Neuroscience, 2018, 38, 9263). In the present study, we investigate the neural basis of this preserved function at the network level. We use generalized psychophysiological interaction and graph theory indices to investigate network level characteristics of the emotion recognition network in TLS patients and healthy controls. Based on conflicting emotion processing theories, we anticipated two possible outcomes: a substantial increase of the non-amygdalar connections of the emotion recognition network to compensate functionally for the loss of the amygdala, in line with basic emotion theory versus only minor changes in network level properties as predicted by psychological construction theory. We defined the emotion recognition network in the total sample and investigated group differences on five network level indices (i.e. characteristic path length, global efficiency, clustering coefficient, local efficiency and small-worldness). The results did not reveal a significant increase in the left or right temporal lobectomy group (compared to the control group) in any of the graph measures, indicating that preserved behavioural emotion recognition in TLS is not associated with a massive connectivity increase between non-amygdalar nodes at network level. We conclude that the emotion recognition network is robust and functionally able to compensate for structural damage without substantial global reorganization, in line with a psychological construction theory.
Programmable shunt valve settings can sometimes be difficult to assess using classic read-out tools, warranting a skull X-ray.Can we use available head computed tomography (CT) scans to determine the valve settings, in order to obviate the need for additional skull X-rays?The valve setting of two different programmable shunts (Codman Certas Plus® and Sophysa Polaris®) were assessed by two blinded observers in 24 patients using 65 head CT scans (slice thickness ≤2 mm). Using multi-planar reconstruction (MPR) tools, images were resliced according to the direction of the valve, allowing a direct readout of the valve settings. We validated our CT based method against 32 available skull X-rays.For all CT scans it was possible to assess the valve setting. No interobserver variability was found and there was a 100 % concordance between the CT based method and skull X-rays.CT based assessment of programmable shunt valve settings is feasible and reliable. It may obviate the need for additional skull x-rays when a head CT scan is available.This technique can reduce radiation exposure and can be applied to historical CT imaging with unknown valve settings.
The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.
Abstract Background CSF leakage is a major complication after cranial surgery, thus, adequate dural closure must be performed. Commercially available fibrin sealants are currently considered the gold standard for dural closure, but problems have been reported regarding safety, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) as an alternative to commercially available fibrin sealants. Methods/design This single-blinded, prospective randomized controlled interventional trial aims to demonstrate the non-inferiority of L-PRF compared to commercially available fibrin sealants for dural closure. This trial will include patients undergoing cranial neurosurgery (supratentorial and infratentorial) with intentional opening of the dura. Patients are randomized in a 1:1 fashion comparing L-PRF to commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage within 12 weeks after surgery. Secondary endpoints are complications such as bleeding or wound infections. Additionally, a cost-effectiveness analysis is performed. Discussion With this trial, we will evaluate the safety and efficiency of L-PRF compared to commercially available fibrin sealants. Trial registration ClinicalTrials.gov NCT03812120. Registered on 22 January 2019.
The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up.
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