8 Feb 2022

Human iPSC-Derived Neural Models for Studying Alzheimer's Disease: from Neural Stem Cells to Cerebral Organoids

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially in the field of Alzheimer's disease (AD), where this treatment is lacking, tremendous effort has been put into the investigation of molecular mechanisms behind this disease using induced pluripotent stem cell-based models. Numerous of these studies have found either novel regulatory mechanisms that could be exploited to develop relevant drugs for AD treatment or have already tested small molecules on in vitro cultures, directly demonstrating their effect on amelioration of AD-associated pathology. This review thus summarizes currently used differentiation strategies of induced pluripotent stem cells towards neuronal and glial cell types and cerebral organoids and their utilization in modeling AD and potential drug discovery.

8 Feb 2022

The reduction of hippocampal volume in Parkinson's disease

The volume of the hippocampus decreases more slowly than the volume of the cortex during normal aging. We explored changes in the hippocampus-to-cortex volume (HV:CTV) ratio with increasing age in non-demented Parkinson's disease (PD) patients as compared to healthy controls (HC). We also evaluated the association between the HV:CTV ratio and cognitive outcomes. Altogether 130 participants without dementia aged 51-88 years were consecutively enrolled, including 54 PD patients (mean age 67, standard deviation (SD) 8 years) and 76 HC (mean age 69, SD 7 years). All participants underwent structural magnetic resonance examination and psychological evaluation. Hippocampal and cortex volumes were determined from T1 and FLAIR scans using FreeSurfer software, and the HV:CTV ratio was calculated. Regression lines for age-dependence of the HV:CTV ratio for PD and HC groups were calculated.

7 Feb 2022

Between-Center Variation in Outcome After Endovascular Treatment of Acute Stroke: Analysis of Two Nationwide Registries

Background: Insight in differences in patient outcomes between endovascular thrombectomy (EVT) centers can help to improve stroke care. We assessed between-center variation in functional outcome of patients with acute ischemic stroke who were treated with EVT. We analyzed to what extent this variation may be explained by modifiable center characteristics.

Methods: We used nationwide registry data of patients with stroke treated with EVT in the Netherlands and in the Czech Republic. Primary outcome was modified Rankin Scale score at 90 days as an indicator of disability. We used multilevel ordinal logistic regression to quantify the between-center variation in outcomes and the impact of patient and center characteristics. 

7 Feb 2022

Emergency cesarean section is a risk factor for depressive symptoms when breastfeeding is limited

Objective: Previous studies indicated associations between cesarean section (CS), breastfeeding, and depressive symptoms. There is, however, little research integrating these variables into one model to analyze their interrelations. The aim of this observational prospective longitudinal study is to examine whether the effect of CS on postpartum depressive symptoms is mediated by difficulties with breastfeeding.

Methods: The participants were recruited in 5 maternity hospitals during their prenatal medical check-ups. Breastfeeding status was self-reported by the mothers six weeks postpartum. Screening for depressive symptoms was performed at six weeks (N = 404) and nine months (N = 234) postpartum using the Edinburgh Postnatal Depression Scale. 

28 Jan 2022

Is the vertex a good control stimulation site? Theta burst stimulation in healthy controls

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs.

28 Jan 2022

Next-generation sequencing in children with epilepsy: The importance of precise genotype-phenotype correlation

Aim: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients.

Methods: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed.

28 Jan 2022

Evaluating Magnetic Resonance Diffusion Properties Together with Brain Volumetry May Predict Progression to Multiple Sclerosis

Rationale and objectives: Although the gold standard in predicting future progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) consists in the McDonald criteria, efforts are being made to employ various advanced MRI techniques for predicting clinical progression. This study's main aim was to evaluate the predictive power of diffusion tensor imaging (DTI) of the brain and brain volumetry to distinguish between patients having CIS with future progression to CDMS from those without progression during the following 2 years and to compare those parameters with conventional MRI evaluation.

Materials and methods: All participants underwent an MRI scan of the brain.

25 Jan 2022

Electrical brain stimulation and continuous behavioral state tracking in ambulatory humans

Objective: Electrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel devices capable of DBS and continuous intracranial EEG (iEEG) telemetry enable detailed assessments of therapy efficacy and tracking sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez's circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).

Approach: The iEEG recorded from HPC is used to classify sleep during concurent DBS targeting ANT.