Connecting the dots: Motor and default mode network crossroads in post-stroke motor learning deficits.

BACKGROUND: Strokes frequently result in long-term motor deficits, imposing significant personal and economic burdens. However, our understanding of the underlying neural mechanisms governing motor learning in stroke survivors remains limited - a fact that poses significant challenges to the development and optimisation of therapeutic strategies. OBJECTIVE: This study investigates the diversity in motor learning aptitude and its associated neurological mechanisms. We hypothesised that stroke patients exhibit compromised overall motor learning capacity, which is associated with altered activity and connectivity patterns in the motor- and default-mode-network in the brain. METHODS: We assessed a cohort of 40 chronic-stage, mildly impaired stroke survivors and 39 age-matched healthy controls using functional Magnetic Resonance Imaging (fMRI) and connectivity analyses. We focused on neural activity and connectivity patterns during an unilateral motor sequence learning task performed with the unimpaired or non-dominant hand. Primary outcome measures included task-induced changes in neural activity and network connectivity. RESULTS: Compared to controls, stroke patients showed significantly reduced motor learning capacity, associated with diminished cerebral lateralization. Task induced activity modulation was reduced in the motor network but increased in the default mode network. The modulated activation strength was associated with an opposing trend in task-induced functional connectivity, with increased connectivity in the motor network and decreased connectivity in the DMN. CONCLUSIONS: Stroke patients demonstrate altered neural activity and connectivity patterns during motor learning with their unaffected hand, potentially contributing to globally impaired motor learning skills. The reduced ability to lateralize cerebral activation, along with the enhanced connectivity between the right and left motor cortices in these patients, may signify maladaptive neural processes that impede motor adaptation, possibly affecting long-term rehabilitation post-stroke. The contrasting pattern of activity modulation and connectivity alteration in the default mode network suggests a nuanced role of this network in post-stroke motor learning. These insights could have significant implications for the development of customised rehabilitation strategies for stroke patients.

Simplifying Multimodal Clinical Research Data Management: Introducing an Integrated and User-friendly Database Concept.

BACKGROUND: Clinical research, particularly in scientific data, grapples with the efficient management of multimodal and longitudinal clinical data. Especially in neuroscience, the volume of heterogeneous longitudinal data challenges researchers. While current research data management systems offer rich functionality, they suffer from architectural complexity that makes them difficult to install and maintain and require extensive user training. OBJECTIVES: The focus is the development and presentation of a data management approach specifically tailored for clinical researchers involved in active patient care, especially in the neuroscientific environment of German university hospitals. Our design considers the implementation of FAIR (Findable, Accessible, Interoperable, and Reusable) principles and the secure handling of sensitive data in compliance with the General Data Protection Regulation. METHODS: We introduce a streamlined database concept, featuring an intuitive graphical interface built on Hypertext Markup Language revision 5 (HTML5)/Cascading Style Sheets (CSS) technology. The system can be effortlessly deployed within local networks, that is, in Microsoft Windows 10 environments. Our design incorporates FAIR principles for effective data management. Moreover, we have streamlined data interchange through established standards like HL7 Clinical Document Architecture (CDA). To ensure data integrity, we have integrated real-time validation mechanisms that cover data type, plausibility, and Clinical Quality Language logic during data import and entry. RESULTS: We have developed and evaluated our concept with clinicians using a sample dataset of subjects who visited our memory clinic over a 3-year period and collected several multimodal clinical parameters. A notable advantage is the unified data matrix, which simplifies data aggregation, anonymization, and export. THIS STREAMLINES DATA EXCHANGE AND ENHANCES DATABASE INTEGRATION WITH PLATFORMS LIKE KONSTANZ INFORMATION MINER (KNIME): . CONCLUSION: Our approach offers a significant advancement for capturing and managing clinical research data, specifically tailored for small-scale initiatives operating within limited information technology (IT) infrastructures. It is designed for immediate, hassle-free deployment by clinicians and researchers.The database template and precompiled versions of the user interface are available at: https://github.com/stebro01/research_database_sqlite_i2b2.git.

[Telemedicine Care of Dementia Patients During the COVID-19 Pandemic]. / Telemedizinische Betreuung von Demenzerkrankten in der COVID-19 Pandemie.

In our multidisciplinary memory center at Jena University Hospital, we initiated a regular video consultation for patients at risk of developing dementia or with dementia disease and their relatives at the beginning of the SARS-CoV2 pandemic in spring 2020.Over a 12-month period, we conducted a systematic survey of satisfaction among patients in regular face-to-face contact (F2F) and video consultations (VC).The aim of this study was to evaluate the potential use of telemedicine in older people with incipient cognitive deficits in the context of dementia. In particular, we aimed to evaluate patient satisfaction and feasibility.Initial presentations to our memory center for suspected dementia were evaluated in a standardized regular on-site setting (n=50) and in a standardized video consultation (n=40). In both settings, a neuropsychologist's and a physician's consultation were performed consecutively. Both groups were similarly distributed in terms of age and sex (71.4 vs. 72.3 years, 52 vs. 50% female (F2F vs. VC)). Cognitive status was slightly better in the VC group (ACE III significant, MMST not significant).In the survey of the patients using a 12-question inventory (patient satisfaction, rated 1 to 5), there was no significant difference between the two groups overall. However, the F2F tended to be rated slightly better here in terms of advice. More than 80% of the physicians and neuropsychologists rated the technical process of VC as good/very good.A general assessment of the cognitive deficits by physicians and neuropsychologists correlated extremely highly with the results of the subsequent specific testing (MMST and ACE) in F2F and VC. With a tendency to better agreement in VC, the difference between the correlations was not significant.Overall, we could not find any significant differences in patients' satisfaction between VC and classical F2F presentation. Technical aspects in the preparation of a VC and during a VC were less problematic than initially anticipated.

Reward network dysfunction is associated with cognitive impairment after stroke.

Stroke survivors not only suffer from severe motor, speech and neurocognitive deficits, but in many cases also from a "lack of pleasure" and a reduced motivational level. Especially apathy and anhedonic symptoms can be linked to a dysfunction of the reward system. Rewards are considered as important co-factor for learning, so the question arises as to why and how this affects the rehabilitation of stroke patients. We investigated reward behaviour, learning ability and brain network connectivity in acute (3-7d) mild to moderate stroke patients (n = 28) and age-matched healthy controls (n = 26). Reward system activity was assessed using the Monetary Incentive Delay task (MID) during magnetoencephalography (MEG). Coherence analyses were used to demonstrate reward effects on brain functional network connectivity. The MID-task showed that stroke survivors had lower reward sensitivity and required greater monetary incentives to improve performance and showed deficits in learning improvement. MEG-analyses showed a reduced network connectivity in frontal and temporoparietal regions. All three effects (reduced reward sensitivity, reduced learning ability and altered cerebral connectivity) were found to be closely related and differed strongly from the healthy group. Our results reinforce the notion that acute stroke induces reward network dysfunction, leading to functional impairment of behavioural systems. These findings are representative of a general pattern in mild strokes and are independent of the specific lesion localisation. For stroke rehabilitation, these results represent an important point to identify the reduced learning capacity after stroke and to implement individualised recovery exercises accordingly.

Evolutionary constraint and innovation across hundreds of placental mammals.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Accuracy of hemodynamic parameters derived by GE E-PiCCO in comparison with PiCCO® in patients admitted to the intensive care unit.

To evaluate the agreement and accuracy of a novel advanced hemodynamic monitoring (AHM) device, the GE E-PiCCO module, with the well-established PiCCO® device in intensive care patients using pulse contour analysis (PCA) and transpulmonary thermodilution (TPTD). A total of 108 measurements were performed in 15 patients with AHM. Each of the 27 measurement sequences (one to four per patient) consisted of a femoral and a jugular indicator injection via central venous catheters (CVC) and measurement using both PiCCO (PiCCO® Jug and Fem) and GE E-PiCCO (GE E-PiCCO Jug and Fem) devices. For statistical analysis, Bland-Altman plots were used to compare the estimated values derived from both devices. The cardiac index measured via PCA (CIpc) and TPTD (CItd) was the only parameter that fulfilled all a priori-defined criteria based on bias and the limits of agreement (LoA) by the Bland-Altman method as well as the percentage error by Critchley and Critchley for all three comparison pairs (GE E-PiCCO Jug vs. PiCCO® Jug, GE E-PiCCO Fem vs. PiCCO® Fem, and GE E-PiCCO Fem vs. GE E-PiCCO Jug), while the GE E-PiCCO did not accurately estimate EVLWI, SVRI, SVV, and PPV values measured via the jugular and femoral CVC compared with values assessed by PiCCO®. Consequently, measurement discrepancy should be considered on evaluation and interpretation of the hemodynamic status of patients admitted to the ICU when using the GE E-PiCCO module instead of the PiCCO® device.

Gait Analysis in Walking and Trotting Dairy Cows on Different Flooring Types with Novel Mobile Pressure Sensors and Inertial Sensors.

Mechanical overburdening is a major risk factor that provokes non-infectious claw diseases. Moreover, lameness-causing lesions often remain undetected and untreated. Therefore, prevention of claw tissue overburdening is of interest, especially by analyzing harmful effects within dairy cows' housing environment. However, objective "on-cow" methods for bovine gait analysis are underdeveloped. The purpose of the study was to apply an innovative mobile pressure sensor system attached at the claws to perform pedobarometric gait analysis. A further goal was the supplementation with accelerative data, generated simultaneously by use of two inertial measurement units (IMUs), attached at metatarsal level. IMU data were analyzed with an automatic step detection algorithm. Gait analysis was performed in ten dairy cows, walking and trotting on concrete flooring and rubber mats. In addition to the basic applicability of the sensor systems and with the aid of the automatic step detection algorithm for gait analysis in cows, we were able to determine the impact of the gait and flooring type on kinematic and kinetic parameters. For pressure sensor output, concrete was associated with significantly (p < 0.001) higher maximum and average pressure values and a significantly smaller contact area, compared to rubber mats. In contrast to walking, trotting led to a significantly higher force, especially under the medial claw. Further, IMU-derived parameters were significantly influenced by the gait. The described sensor systems are useful tools for detailed gait analysis in dairy cows. They allow the investigation of factors which may affect claw health negatively.

Still Wanting to Win: Reward System Stability in Healthy Aging.

Healthy aging is accompanied by multi-faceted changes. Especially within the brain, healthy aging exerts substantial impetus on core parts of cognitive and motivational networks. Rewards comprise basic needs, such as food, sleep, and social contact. Thus, a functionally intact reward system remains indispensable for elderly people to cope with everyday life and adapt to their changing environment. Research shows that reward system function is better preserved in the elderly than most cognitive functions. To investigate the compensatory mechanisms providing reward system stability in aging, we employed a well-established reward paradigm (Monetary Incentive Delay Task) in groups of young and old participants while undergoing EEG measurement. As a new approach, we applied EEG connectivity analyses to assess cortical reward-related network connectivity. At the behavioral level, our results confirm that the function of the reward system is preserved in old age. The mechanisms identified for maintaining reward system function in old age do not fit into previously described models of cognitive aging. Overall, older adults exhibit lower reward-related connectivity modulation, higher reliance on posterior and right-lateralized brain areas than younger adults, and connectivity modulation in the opposite direction than younger adults, with usually greater connectivity during non-reward compared to reward conditions. We believe that the reward system has unique compensatory mechanisms distinct from other cognitive functions, probably due to its etymologically very early origin. In summary, this study provides important new insights into cortical reward network connectivity in healthy aging.

A therian mammal with sprawling kinematics? Gait and 3D forelimb X-ray motion analysis in tamanduas.

Therian mammals are known to move their forelimbs in a parasagittal plane, retracting the mobilised scapula during stance phase. Non-cursorial therian mammals often abduct the elbow out of the shoulder-hip parasagittal plane. This is especially prominent in Tamandua (Xenarthra), which suggests they employ aspects of sprawling (e.g. lizard-like) locomotion. Here, we tested whether tamanduas use sprawling forelimb kinematics, i.e. a largely immobile scapula with pronounced lateral spine bending and long-axis rotation of the humerus. We analysed high-speed videos and used X-ray motion analysis of tamanduas walking and balancing on branches of varying inclinations and provide a quantitative characterization of gaits and forelimb kinematics. Tamanduas displayed lateral sequence/lateral couplets on flat ground and horizontal branches, but increased diagonality on steeper inclines and declines, resulting in lateral sequence/diagonal couplets gaits. This result provides further evidence for high diagonality in arboreal species, probably maximising stability in arboreal environments. Further, the results reveal a mosaic of sprawling and parasagittal kinematic characteristics. The abducted elbow results from a constantly internally rotated scapula about its long axis and a retracted humerus. Scapula retraction contributes considerably to stride length. However, lateral rotation in the pectoral region of the spine (range: 21 deg) is higher than reported for other therian mammals. Instead, it is similar to that of skinks and alligators, indicating an aspect generally associated with sprawling locomotion is characteristic for forelimb kinematics of tamanduas. Our study contributes to a growing body of evidence of highly variable non-cursorial therian mammal locomotor kinematics.

Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor PNLIPRP1 and the xenobiotic receptor NR1I3.

The inactivation of ancestral protein-coding genes (gene loss) can be associated with phenotypic modifications. Within placental mammals, repeated losses of PNLIPRP1 (gene inhibiting fat digestion) occurred preferentially in strictly herbivorous species, whereas repeated NR1I3 losses (gene involved in detoxification) occurred preferentially in strictly carnivorous species. It was hypothesized that lower fat contents of herbivorous diets and lower toxin contents of carnivorous diets cause relaxed selection pressure on these genes, resulting in the accumulation of mutations and ultimately to convergent gene losses. However, because herbivorous and carnivorous diets differ vastly in their composition, a fine-grained analysis is required for hypothesis testing. We generated a trait matrix recording diet and semi-quantitative estimates of fat and toxin consumption for 52 placental species. By including data from 31 fossil taxa, we reconstructed the ancestral diets in major lineages (grundplan reconstruction). We found support that PNLIPRP1 loss is primarily associated with low levels of fat intake and not simply with herbivory/carnivory. In particular, PNLIPRP1 loss also occurred in carnivorous lineages feeding on a fat-poor diet, suggesting that the loss of this gene may be beneficial for occupying ecological niches characterized by fat-poor food resources. Similarly, we demonstrated that carnivorous species are indeed less exposed to diet-related toxins, suggesting that the loss of NR1I3 and related genes (NR1I2 and UGT1A6) resulted from relaxed selection pressure. This study illustrates the need of detailed phenotype studies to obtain a deeper understanding of factors underlying gene losses and to progress in understanding genomic causes of phenotypic variation in mammals.

A novel giant non-cholinergic striatal interneuron restricted to the ventrolateral striatum coexpresses Kv3.3 potassium channel, parvalbumin, and the vesicular GABA transporter.

The striatum is the main input structure of the basal ganglia. Distinct striatal subfields are involved in voluntary movement generation and cognitive and emotional tasks, but little is known about the morphological and molecular differences of striatal subregions. The ventrolateral subfield of the striatum (VLS) is the orofacial projection field of the sensorimotor cortex and is involved in the development of orofacial dyskinesias, involuntary chewing-like movements that often accompany long-term neuroleptic treatment. The biological basis for this particular vulnerability of the VLS is not known. Potassium channels are known to be strategically localized within the striatum. In search of possible molecular correlates of the specific vulnerability of the VLS, we analyzed the expression of voltage-gated potassium channels in rodent and primate brains using qPCR, in situ hybridization, and immunocytochemical single and double staining. Here we describe a novel, giant, non-cholinergic interneuron within the VLS. This neuron coexpresses the vesicular GABA transporter, the calcium-binding protein parvalbumin (PV), and the Kv3.3 potassium channel subunit. This novel neuron is much larger than PV neurons in other striatal regions, displays characteristic electrophysiological properties, and, most importantly, is restricted to the VLS. Consequently, the giant striatal Kv3.3-expressing PV neuron may link compromised Kv3 channel function and VLS-based orofacial dyskinesias.

Differences in Cell-Intrinsic Inflammatory Programs of Yolk Sac and Bone Marrow Macrophages.

BACKGROUND: Tissue-resident macrophages have mixed developmental origins. They derive in variable extent from yolk sac (YS) hematopoiesis during embryonic development. Bone marrow (BM) hematopoietic progenitors give rise to tissue macrophages in postnatal life, and their contribution increases upon organ injury. Since the phenotype and functions of macrophages are modulated by the tissue of residence, the impact of their origin and developmental paths has remained incompletely understood. METHODS: In order to decipher cell-intrinsic macrophage programs, we immortalized hematopoietic progenitors from YS and BM using conditional HoxB8, and carried out an in-depth functional and molecular analysis of differentiated macrophages. RESULTS: While YS and BM macrophages demonstrate close similarities in terms of cellular growth, differentiation, cell death susceptibility and phagocytic properties, they display differences in cell metabolism, expression of inflammatory markers and inflammasome activation. Reduced abundance of PYCARD (ASC) and CASPASE-1 proteins in YS macrophages abrogated interleukin-1ß production in response to canonical and non-canonical inflammasome activation. CONCLUSIONS: Macrophage ontogeny is associated with distinct cellular programs and immune response. Our findings contribute to the understanding of the regulation and programming of macrophage functions.

Cyclic tensile tests of Shetland pony superficial digital flexor tendons (SDFTs) with an optimized cryo-clamp combined with biplanar high-speed fluoroscopy.

BACKGROUND: Long-term cyclic tensile testing with equine palmar/plantar tendons have not yet been performed due to problems in fixing equine tendons securely and loading them cyclically. It is well established that the biomechanical response of tendons varies during cyclic loading over time. The aim of this study was to develop a clamping device that enables repetitive cyclic tensile testing of equine superficial digital flexor tendon for at least 60 loading cycles and for 5 min. RESULTS: A novel cryo-clamp was developed and built. Healthy and collagenase-treated pony SDFTs were mounted in the custom-made cryo-clamp for the proximal tendon end and a special clamping device for the short pastern bone (os coronale). Simultaneously with tensile testing, we used a biplanar high-speed fluoroscopy system (FluoKin) to track tendon movement. The FluoKin system was additionally validated in precision measurements. During the cyclic tensile tests of the SDFTs, the average maximal force measured was 325 N and 953 N for a length variation of 2 and 4 % respectively. The resulting stress averaged 16 MPa and 48 MPa respectively, while the modulus of elasticity was 828 MPa and 1212 MPa respectively. Length variation of the metacarpal region was, on average, 4.87 % higher after incubation with collagenase. The precision of the FluoKin tracking was 0.0377 mm, defined as the standard deviation of pairwise intermarker distances embedded in rigid bodies. The systems accuracy was 0.0287 mm, which is the difference between the machined and mean measured distance. CONCLUSION: In this study, a good performing clamping technique for equine tendons under repetitive cyclic loading conditions is described. The presented cryo-clamps were tested up to 50 min duration and up to the machine maximal capacity of 10 kN. With the possibility of repetitive loading a stabilization of the time-force-curve and changes of hysteresis and creep became obvious after a dozen cycles, which underlines the necessity of repetitive cyclical testing. Furthermore, biplanar high-speed fluoroscopy seems an appropriate and highly precise measurement tool for analysis of tendon behaviour under repetitive load in equine SDFTs.

Biplanar High-Speed Fluoroscopy of Pony Superficial Digital Flexor Tendon (SDFT)-An In Vivo Pilot Study.

The superficial digital flexor tendon (SDFT) is the most frequently injured structure of the musculoskeletal system in sport horses and a common cause for early retirement. This project's aim was to visualize and measure the strain of the sound, injured, and healing SDFTs in a pony during walk and trot. For this purpose, biplanar high-speed fluoroscopic kinematography (FluoKin), as a high precision X-ray movement analysis tool, was used for the first time in vivo with equine tendons. The strain in the metacarpal region of the sound SDFT was 2.86% during walk and 6.78% during trot. When injured, the strain increased to 3.38% during walk and decreased to 5.96% during trot. The baseline strain in the mid-metacarpal region was 3.13% during walk and 6.06% during trot and, when injured, decreased to 2.98% and increased to 7.61%, respectively. Following tendon injury, the mid-metacarpal region contributed less to the overall strain during walk but showed increased contribution during trot. Using this marker-based FluoKin technique, direct, high-precision, and long-term strain measurements in the same individual are possible. We conclude that FluoKin is a powerful tool for gaining deeper insight into equine tendon biomechanics.

"Forever young"-Postnatal growth inhibition of the turbinal skeleton in brachycephalic dog breeds (Canis lupus familiaris).

In short snouted (brachycephalic) dogs (Canis lupus familiaris), several genetic mutations cause postnatal growth inhibition of the viscerocranium. Thus, for example, the pug keeps a snub nose like that observed in neonate dogs in general. However, little is known how far intranasal structures like the turbinal skeleton are also affected. In the present study, we provide the first detailed morphological and morphometric analyses on the turbinal skeleton of pug, Japanese chin, pekingese, King Charles spaniel, and Cavalier. In order to elucidate how a shortened snout affects turbinal shape, size, and density, our sample covers different degrees of brachycephaly. Macerated skulls of 1 juvenile and 17 adult individuals were investigated by µCT and virtual 3D reconstructions. In addition, histological serial sections of two prenatal and one neonate whippet were taken into account. All investigated postnatal stages show three frontoturbinals and three ethmoturbinals similar to longer snouted breeds, whereas the number of interturbinals is reduced. The shape of the entire turbinal skeleton simplifies with decreasing snout length, that is, within a minimized nasal cavity the turbinals decrease proportionally in surface area and surface density due to a looser arrangement. We interpret these apparent reductions as a result of spatial constraint which affects postnatal appositional bone growth and the position of the turbinals inside the nasal cavity. The turbinal skeleton of brachycephalic dogs arrests at an early ontogenetic stage, corresponding with previous studies on the dermal bones. Hence, we assume an association between the growth of intranasal structures and facial elongation.

Performance of pacemaker leads in alternative lead positions after tricuspid valve replacement.

BACKGROUND: Bradycardic arrhythmias requiring pacemaker (PM) implantation are still common in patients in need of tricuspid valve replacement (TVR). Leaving an existing PM lead in an extravalvular position may represent a helpful alternative in special situations like the implantation of a mechanical TV. This study aimed to examine the short- to mid-term outcome of paravalvular leads concerning lead survival and prosthesis dysfunction in patients after TVR. METHODS: A retrospective case-control study of patients with TVR and ventricular pacing was conducted. Patients from the database of the Leipzig Heart Center were included. Data of the paravalvular lead group (PVG) and coronary sinus lead group (CSG) were compared to a control group with conventional transvalvular leads (TVG). RESULTS: Eighty patients with TVR and cardiac PM (TVG [n = 13], PVG [n = 40], and CSG [n = 27]) were included. The mean follow-up was 2.8 years. The rate of lead revisions (TVG 15.4%, PVG 2.5%, and CSG 7.5%) was lower in PVG but without significance (P = .286). The CSG demonstrated significantly higher pacing thresholds (1.4 V/0.8 ms) than TVG (0.5 V/0.4 ms), P = .004. However, the deterioration of threshold amplitudes during follow-up was similar in CSG (7.4%) and PVG (7.5%) compared with controls (7.7%). Function of TV prosthesis regarding development of stenosis or regurgitation showed a similarity between the groups (regurgitation PVG P = .692, CSG P = 1; stenosis PVG P = .586, CSG P = 0.69). CONCLUSION: Paravalvular positioning of PM leads seems to represent a reasonable alternative to the conventional transvalvular lead positioning concerning the lead and Tricuspid Valve prosthesis's function and durability in selected patients.

Detailed morphological analysis of rat hippocampi treated with CSF autoantibodies from patients with anti-NMDAR encephalitis discloses two distinct types of immunostaining patterns.

Anti-NMDA receptor encephalitis was first described about thirteen years ago and has become one of the most important differential diagnoses for new-onset psychosis. The disease is mediated by autoantibodies against the subunit 1 of the N-methyl-D-aspartate receptor (NMDA-R1) in patients presenting with variable clinical symptoms. Patients often profit from immunmodulatory therapy, independent of their individual symptoms. In this study CSF samples as well as monoclonal antibodies derived from patients diagnosed with NMDA-R1 encephalitis were applied to rat hippocampus and visualized by immunocytochemistry. This reveals at least two distinct patterns of immunoreactivity. Antibodies from "pattern group 1" display the familiar pattern of NMDA-R1 distribution in the hippocampus reported in experiments with rabbit anti-NMDA-R1 antibodies. Neurons and primary dendrites in the CA1 and CA3 region show strongly stained cell bodies, in line with the predominant postsynaptic localization of the NMDA receptor in the brain. However, autoantibodies from "pattern group 2" show an inverse pattern, with no staining of the cell bodies and primary dendrites in CA1 and CA3 regions. Electron microscopic experiments disclose that autoantibodies of "pattern group 1 patients" bind to postsynaptic NMDA receptors, while those of "pattern group 2 patients" target presynaptic NMDA receptors. We describe one NMDA-receptor antibody giving staining comparable to rabbit anti-NMDA-R1 antibodies, raised against the C-terminus. In the highly heterogenous disease anti-NMDA-receptor 1 encephalitis we found evidence for at least two different subtypes. It will be very interesting to determine whether there also are two distinct clinical phenotypes.

Quality of life and psychological co-morbidities in children and adolescents with cardiac pacemakers and implanted defibrillators: a cohort study in Eastern Germany.

INTRODUCTION: The implantation of a pacemaker or an implantable cardioverter-defibrillator during childhood may reduce quality of life and lead to mental health problems. This study aimed to evaluate potential mental health problems (i.e., depressive and anxiety symptoms) and quality of life in children with cardiac active devices in comparison to healthy peers. METHODS: We analysed data of children with pacemakers or implantable cardioverter-defibrillators aged 6-18 years. Quality of life, depressive and anxiety symptoms were assessed by standardised questionnaires. The results were compared to age-matched reference groups. RESULTS: Children with implantable cardioverter-defibrillator showed significant lower quality of life in comparison to reference group (p = 0.03), but there was no difference in quality of life between children with pacemaker and reference group. There was no significant difference in depressive symptoms between children with a cardiac rhythm device compared to reference group (self-report: p = 0.67; proxy report: p = 0.49). There was no significant difference in anxiety (p = 0.53) and depressive symptoms (p = 0.86) between children with pacemaker and children with implantable cardioverter-defibrillator. CONCLUSIONS: Living with an implantable cardioverter-defibrillator in childhood seems to decrease the patients' quality of life. Although children with pacemaker and implantable cardioverter-defibrillator don't seem to show more depressive and anxiety symptoms in comparison to their healthy peers, there still can be an increased risk for those children to develop mental health problems. Therefore, treating physicians should be aware of potential mental health problems and provide the patients and their families with appropriate therapeutic offers.