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Objective: Up to a third of patients with epilepsy fail to achieve satisfactory seizure control. A reliable method of predicting seizures would alleviate psychological and physical impact. Dysregulation in heart rate variability (HRV) has been found to precede epileptic seizures and may serve as an extracerebral predictive biomarker. This study aims to identify the preictal HRV dynamics and unveil the factors impeding the clinical application of ECG-based seizure prediction., Methods: Thirty-nine adult patients (eight women; median age: 38, [IQR = 31, 56.5]) with 252 seizures were included. Each patient had more than three recorded epileptic seizures, each at least 2 hours apart. For each seizure, one hour of ECG prior to seizure onset was analyzed and 97 HRV features were extracted from overlapping three-minute windows with 10s stride. Two separate patient-specific experiments were performed using a support vector machine (SVM). Firstly, the separability of training data was examined in a non-causal trial. Secondly, the prediction was attempted in pseudo-prospective conditions. Finally, visualized HRV data, clinical metadata, and results were correlated., Results: The mean receiver operating characteristic (ROC) area under the curve (AUC) for the non-causal experiment was 0.823 (±0.12), with 208 (82.5%) seizures achieving an improvement over chance (IoC) classification score (p < 0.05, Hanley & McNeil test). In pseudo-prospective classification, the ROC-AUC was 0.569 (±0.17), and 86 (49.4%) seizures were classified with IoC. Off-sample optimized SVMs failed to improve performance. Major limiting factors identified include non-stationarity, variable preictal duration and dynamics. The latter is expressed as both inter-seizure onset zone (SOZ) and intra-SOZ variability., Significance: The pseudo-prospective preictal classification achieving IoC in approximately half of tested seizures suggests the presence of genuine preictal HRV dynamics, but the overall performance does not warrant clinical application at present. The limiting factors identified are often overlooked in non-causal study designs. While current deterministic prediction methods prove inadequate, probabilistic approaches may offer a promising alternative., Plain Language Summary: Many patients with epilepsy suffer from uncontrollable seizures and would greatly benefit from a reliable seizure prediction method. Currently, no such system is available to meet this need. Previous studies suggest that changes in the electrocardiogram (ECG) precede seizures by several minutes. In our work, we evaluated whether variations in heart rate could be used to predict epileptic seizures. Our findings indicate that we are still far from achieving results suitable for clinical application and highlight several limiting factors of present seizure prediction approaches., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: The apparent randomness of seizure occurrence affects greatly the quality of life of persons with epilepsy. Since seizures are often phase-locked to multidien cycles of interictal epileptiform activity, a recent forecasting scheme, exploiting RNS data, is capable of forecasting seizures days in advance., Methods: We tested the use of a bandpass filter to capture the universal mid-term dynamics enabling both patient-specific and cross-patient forecasting. In a retrospective study, we explored the feasibility of the scheme on three long-term recordings obtained by the NeuroPace RNS System, the NeuroVista intracranial, and the UNEEG subcutaneous devices, respectively., Results: Better-than-chance forecasting was observed in 15 (83 %) of 18 patients, and in 16 (89 %) patients for daily and hourly forecast, respectively. Meaningful forecast up to 30 days could be achieved in 4 (22 %) patients for hourly forecast frequency. The cross-patient performance decreased only marginally and was patient-wise strongly correlated with the patient-specific one. Comparable performance was obtained for NeuroVista and UNEEG data sets., Significance: The feasibility of cross-patient forecasting supports the universal importance of mid-term dynamics for seizure forecasting, demonstrates promising inter-subject-applicability of the scheme on ultra long-term EEG recordings, and highlights its huge potential for clinical use., Competing Interests: Declaration of Competing Interest J.D.-H. is a full-time employee at UNEEG medical, a company developing and producing a subscalp EEG device. T.K. has performed consultancy for UNEEG medical. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Brain activity may manifest itself as oscillations which are repetitive rhythms of neuronal firing. These local field potentials can be measured via intracranial electroencephalography (iEEG). This review focuses on iEEG used to map human brain structures involved in olfaction. After presenting the methodology of the review, a summary of the brain structures involved in olfaction is given, followed by a review of the literature on human olfactory oscillations in different contexts. A single case is provided as an illustration of the olfactory oscillations. Overall, the timing and sequence of oscillations found in the different structures of the olfactory system seem to play an important role for olfactory perception., (© 2024 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Objective: Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE., Methods: Nine patients with TLE and depression/anxiety underwent 11 C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex., Results: We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus., Significance: In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored., Methods: EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo., Results: In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3β, and transcription factors, including HIF1α, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo., Conclusions: Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored., (© 2023. The Author(s).)

A paired-catchment study of two adjacent commercial areas in northern Sweden, one with Green Infrastructure (GI) storm drainage and the other with a conventional storm sewer system, served to evaluate the hydrological performance of both drainage systems and demonstrate advantages of GI. The GI catchment avoided directly connected impervious areas by diverting runoff from a parking lot to a cascade of three infiltration features, a fractured rock strip draining onto a sloping infiltration area, followed by a collector swale. Both catchments were monitored over 4 years by measuring rainfall, runoff and, in the vicinity of the swale, soil water content and groundwater levels. For frequent storms, the median GI efficiencies in reducing runoff volumes and peak flows, and extending peak flow lags, were 96, 99 and 60%, respectively, compared to conventional drainage. The storm rainfall depth, initial soil water content, increases in intra-event soil water storage and groundwater levels had statistically significant effects on either runoff volume or peak flow reductions. No effects were found for storm rainfall intensity and duration, antecedent dry days, and initial groundwater levels. The study demonstrated that GI drainage can be successfully applied even in the challenging environment of a subarctic climate.

Objective: Seizure forecasting using machine learning is possible, but the performance is far from ideal, as indicated by many false predictions and low specificity. Here, we examine false and missing alarms of two algorithms on long-term datasets to show that the limitations are less related to classifiers or features, but rather to intrinsic changes in the data., Methods: We evaluated two algorithms on three datasets by computing the correlation of false predictions and estimating the information transfer between both classification methods., Results: For 9 out of 12 individuals both methods showed a performance better than chance. For all individuals we observed a positive correlation in predictions. For individuals with strong correlation in false predictions we were able to boost the performance of one method by excluding test samples based on the results of the second method., Conclusions: Substantially different algorithms exhibit a highly consistent performance and a strong coherency in false and missing alarms. Hence, changing the underlying hypothesis of a preictal state of fixed time length prior to each seizure to a proictal state is more helpful than further optimizing classifiers., Significance: The outcome is significant for the evaluation of seizure prediction algorithms on continuous data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Enrichment of soils in three urban drainage swales by metals associated with traffic sources was investigated in a cool temperate climate with seasonal snow. Such swales differed from those not exposed to snow by receiving additional pollutant loads from winter road maintenance involving applications of salt and grit, use of studded tires, and storage and melting of polluted snow cleared from trafficked areas into swales. Among the swales studied, swale L2 in the downtown was the oldest (built around 1960), drained runoff from a road with the highest traffic intensity, and exhibited the highest mean concentrations of most of the metals studied (Pb, Cu, Zn, Cr, Cd, Ni, Co, V, Ti, and W). In the case of Pb, this exceedance was about an order of magnitude: 71 mg/kg DW in L2, compared to about ~8 mg/kg DW in L1 and L3, both built in 1979. Among the metals originating from local geology, barium (Ba) was found in the swales and the grit material at high concentrations of ~650 mg/kg DW and 700-1000 mg/kg DW, respectively. Such concentrations exceeded the Swedish EPA guideline limits of 300 mg/kg DW for less sensitive soil use. The sequential extraction analysis of samples from swale L2 indicated that Ba was mostly in the immobile residual fraction (90%). The absence of clear decline in metal concentrations with distance from the trafficked surfaces suggested that stored snow was another source of metals partly balancing spatial distribution of metals in swale soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Swales are the oldest and most common stormwater control measure for conveying and treating roadway runoff worldwide. Swales are also gaining popularity as part of stormwater treatment trains and as crucial elements in green infrastructure to build more resilient cities. To achieve higher pollutant reductions, swale alternatives with engineered media (bioswales) and wetland conditions (wet swales) are being tested. However, the available swale design guidance is primarily focused on hydraulic conveyance, overlooking their function as an important water quality treatment tool. The objective of this article is to provide science-based swale design guidance for treating targeted pollutants in stormwater runoff. This guidance is underpinned by a literature review. The results of this review suggest that well-maintained grass swales with check dams or infiltration swales are the best options for runoff volume reduction and removal of sediment and heavy metals. For nitrogen removal, wet swales are the most effective swale alternative. Bioswales are best for phosphorus and bacteria removal; both wet swales and bioswales can also treat heavy metals. Selection of a swale type depends on the site constraints, local climate, and available funding for design, construction, and operation. Appropriate siting, pre-design site investigations, and consideration of future maintenance during design are critical to successful long-term swale performance. Swale design recommendations based on a synthesis of the available research are provided, but actual design standards should be developed using local empirical data. Future research is necessary to identify optimal design parameters for all swale types, especially for wet swales., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Increasing interest in urban drainage green infrastructure brings attention to grass swales and filter strips (GS&GFS) and their role in stormwater management. While the understanding of the hydrology and hydraulics of these stormwater control measures is adequate for current needs, there are knowledge gaps in understanding the water quality processes in GS&GFS and such a finding motivated preparation of the review paper that follows. The review revealed that most of the empirical studies of GS&GFS flow quality focused on the removal of pollutants associated with road runoff, and particularly solids, with relatively few studies addressing nutrients, traffic associated hydrocarbons, oxygen demanding substances, chloride, and faecal indicator bacteria. The reported results suffer from limitations caused by experimental conditions often representing a steady flow used to irrigate GS&GFS and generate runoff, non-submerged flows, no lateral inflows along swale side slopes, constant dosing of solids, emphasis on larger-than-typical solids, incomplete descriptions of experimental conditions, and limited attention to experimental uncertainties. Besides settling, other treatment processes, like adsorption/desorption, plant uptake, chemical precipitation and microbial degradation are often acknowledged, but without attempting to quantify their effects on flow quality. The modelling of GS&GFS flow quality would be beneficial for an improved understanding of green urban drainage infrastructure, but currently it is infeasible without a better knowledge of stormwater quality processes in GS&GFS facilities., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD"., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589-601. ©2017 AACR ., (©2017 American Association for Cancer Research.)

In the urban water cycle, there are different ways of handling stormwater runoff. Traditional systems mainly rely on underground piped, sometimes named 'gray' infrastructure. New and so-called 'green/blue' ambitions aim for treating and conveying the runoff at the surface. Such concepts are mainly based on ground infiltration and temporal storage. In this work a methodology to create and compare different planning alternatives for stormwater handling on their pathways to a desired system state is presented. Investigations are made to assess the system performance and robustness when facing the deeply uncertain spatial and temporal developments in the future urban fabric, including impacts caused by climate change, urbanization and other disruptive events, like shifts in the network layout and interactions of 'gray' and 'green/blue' structures. With the Info-Gap robustness pathway method, three planning alternatives are evaluated to identify critical performance levels at different stages over time. This novel methodology is applied to a real case study problem where a city relocation process takes place during the upcoming decades. In this case study it is shown that hybrid systems including green infrastructures are more robust with respect to future uncertainties, compared to traditional network design.

Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Existence of nuclear spheres in the human brain was studied using immunohistochemistry. Cell culture experiments were used to study regulative mechanisms of nuclear sphere generation. The comparison of human frontal cortex brain samples from Alzheimer's disease (AD) patients to age-matched controls revealed a dramatically and highly significant enrichment of nuclear spheres in the AD brain. Costaining demonstrated that neurons are distinctly affected by nuclear spheres, but astrocytes never are. Nuclear spheres were predominantly found in neurons that were negative for threonine 668 residue in APP phosphorylation. Cell culture experiments revealed that JNK3-mediated APP phosphorylation reduces the amount of sphere-positive cells. The study suggests that nuclear spheres are a new APP-derived central hallmark of AD, which might be of crucial relevance for the molecular mechanisms in neurodegeneration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A central molecular hallmark of Alzheimer's disease (AD) is the β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP), which causes the generation of different c-terminal fragments like C99, AICD57, or AICD50 that fully or in part contain the APP transmembrane domain. In this study, we demonstrate that membrane-tethered C99 is phosphorylated by JNK3A at residue T668 (APP695 numbering) to a higher extent than AICD57, whereas AICD50 is not capable of being phosphorylated. The modification decreases the turnover of APP, while the blockade of APP cleavage increases APP phosphorylation. Generation of nuclear spheres, complexes consisting of the translocated AICD, FE65 and other proteins, is significantly reduced as soon as APP c-terminal fragments are accessible for phosphorylation. This APP modification, which we identified as significantly reduced in high plaque-load areas of the human brain, is linearly dependent on the level of APP expression. Accordingly, we show that APP abundance is likewise capable of modulating nuclear sphere generation. Thus, the precise and complex regulation of APP phosphorylation, abundance, and cleavage impacts the generation of nuclear spheres, which are under discussion of being of relevance in neurodegeneration and dementia. Future pharmacological manipulation of nuclear sphere generation may be a promising approach for AD treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The assessment of future trends in urban stormwater quality should be most helpful for ensuring the effectiveness of the existing stormwater quality infrastructure in the future and mitigating the associated impacts on receiving waters. Combined effects of expected changes in climate and socio-economic factors on stormwater quality were examined in two urban test catchments by applying a source-based computer model (WinSLAMM) for TSS and three heavy metals (copper, lead, and zinc) for various future scenarios. Generally, both catchments showed similar responses to the future scenarios and pollutant loads were generally more sensitive to changes in socio-economic factors (i.e., increasing traffic intensities, growth and intensification of the individual land-uses) than in the climate. Specifically, for the selected Intermediate socio-economic scenario and two climate change scenarios (RSP = 2.6 and 8.5), the TSS loads from both catchments increased by about 10 % on average, but when applying the Intermediate climate change scenario (RCP = 4.5) for two SSPs, the Sustainability and Security scenarios (SSP1 and SSP3), the TSS loads increased on average by 70 %. Furthermore, it was observed that well-designed and maintained stormwater treatment facilities targeting local pollution hotspots exhibited the potential to significantly improve stormwater quality, however, at potentially high costs. In fact, it was possible to reduce pollutant loads from both catchments under the future Sustainability scenario (on average, e.g., TSS were reduced by 20 %), compared to the current conditions. The methodology developed in this study was found useful for planning climate change adaptation strategies in the context of local conditions.

Pregnancy due to its physiological changes is a procoagulant state. The rate of cardiac valve prosthesis thrombosis, deep venous thrombosis and pulmonary embolism are all increased. Thrombolytic therapy with tissue plasminogen activator (rt-PA) is an approved therapy for ischemic stroke, myocardial infarction, pulmonary embolism and thrombosis of cardiac valve prosthesis. However, there are no data from controlled randomized trials in pregnant patients. Thrombolytic therapy has been rarely used in pregnancy with only 28 cases of rt-PA thrombolysis reported in the literature so far. Indications for rt-PA thrombolysis were stroke (n = 10), thrombosis of cardiac valve prosthesis (n = 7), pulmonary embolism (n = 7), deep venous thrombosis (n = 3), and myocardial infarction (n = 1). Remarkably, all thrombosis of cardiac valve prostheses occurred after switching from warfarin to heparin in order to prevent teratogenicity and fetal loss. Two patients died (7%) and three suffered from complications that were managed conservatively (11%). In another three patients thrombolysis was not successful. Thrombolysis complication rates were similar compared to non-pregnant patients for the above mentioned indications. Six out of the 26 fetus from surviving mothers died (23%), three of them after induced abortion for maternal reasons (12%). A likely causal relation to the prior thrombolysis could only be established in two fetal fatalities (8%). None of the live born children suffered a permanent deficit. Considering that rt-PA does not cross the placenta and taking into account that the complication rates do not exceed those of large randomised controlled trials thrombolytic therapy should not be withheld in pregnant patients in case of life-threatening or potentially debilitating thrombembolic disease.

Purpose: The aim of this study was to assess the regional relative interictal and postictal perfusion changes in temporal and parietal lobe epilepsy., Methods: We investigated interictal and postictal magnet resonance perfusion changes in five patients with temporal lobe epilepsy either with hippocampal sclerosis (n = 3) or without (n = 2), and in one patient with extratemporal (parietal lobe) epilepsy. T(2)*-weighted single-shot echo-planar images were acquired after bolus application of 0.2 mmol/kg gadolinium-diethylene triamine pentaacetic acid (GD-DTPA) at baseline and after intervals of 2-12 min, 15-23 min, 28-50 min, 63-72 min, and 180-240 min. The bolus-peak ratio was calculated in regions of interest in the hippocampus (HIP), parahippocampal gyrus (PHG), thalamus (THA), cortex (COR), and white matter (WM), yielding relative perfusion changes., Results: Interictally, we found relative hyperperfusion of the ictogenic side in five of six patients in the HIP. Postictally, the perfusion decreased in the HIP by 25-39% as compared to baseline, whereas the PHG showed a reverse pattern. In the late postictal phase, perfusion increased in the HIP again and decreased in the PHG. In the THA, the inter- and postictal changes were small (5-19%). COR and WM showed equivocal results., Conclusion: Postictal relative hypoperfusion in the HIP appears to be associated with the cessation of neuronal ictal discharge, whereas postictal hyperperfusion in the PHG lags behind and may reflect increased metabolism to restore the interictal state of neuronal excitability.

Background: Differential diagnosis of acute tetraparesis includes paraplegia caused by trauma, ischemia, inflammation or tumor, Guillain-Barré syndrome, periodic paralysis, myasthenia gravis, and dissociative paralysis., Case Report: The case of a 45-year-old man is reported who noticed weakness of both legs after heavy labor. In the evening he was unable to climb stairs, at night he noticed additional weakness in both arms and dyspnea. After transfer to the authors' department profound tetraparesis, tachycardia and slight dyspnea were found on examination. Cranial nerve examination was unremarkable. Deep tendon reflexes, however, were only slightly diminished. Laboratory work-up revealed hypokalemia (potassium 1.9 mmol/l) and hyperthyreosis. Elevated TRAK and TPO antibodies as well as sonography and scintigraphy of the thyroid gland gave evidence of Graves' disease. After intravenous administration of potassium tetraparesis resolved completely., Conclusion: Hypokalemic thyrotoxic periodic paralysis (HTPP), a subtype of hypokalemic paralysis, is unusual in Caucasians. In Asian men the disease is more common. The underlying mechanism is an extra-intracellular shift of potassium in the voluntary muscle cells. In contrast to hereditary autosomal dominant paralyses, a genetic defect is not known. Usually, symptoms of hyperthyreosis in HTPP are mild which can hamper the correct diagnosis.

Oligomer-based DNA Affymetrix GeneChips representing about one-third of Arabidopsis (Arabidopsis thaliana) genes were used to profile global gene expression in a single cell type, guard cells, identifying 1309 guard cell-expressed genes. Highly pure preparations of guard cells and mesophyll cells were isolated in the presence of transcription inhibitors that prevented induction of stress-inducible genes during cell isolation procedures. Guard cell expression profiles were compared with those of mesophyll cells, resulting in identification of 64 transcripts expressed preferentially in guard cells. Many large gene families and gene duplications are known to exist in the Arabidopsis genome, giving rise to redundancies that greatly hamper conventional genetic and functional genomic analyses. The presented genomic scale analysis identifies redundant expression of specific isoforms belonging to large gene families at the single cell level, which provides a powerful tool for functional genomic characterization of the many signaling pathways that function in guard cells. Reverse transcription-PCR of 29 genes confirmed the reliability of GeneChip results. Statistical analyses of promoter regions of abscisic acid (ABA)-regulated genes reveal an overrepresented ABA responsive motif, which is the known ABA response element. Interestingly, expression profiling reveals ABA modulation of many known guard cell ABA signaling components at the transcript level. We further identified a highly ABA-induced protein phosphatase 2C transcript, AtP2C-HA, in guard cells. A T-DNA disruption mutation in AtP2C-HA confers ABA-hypersensitive regulation of stomatal closing and seed germination. The presented data provide a basis for cell type-specific genomic scale analyses of gene function.

Purpose: After focal status epilepticus, focal alterations of the apparent diffusion coefficient (ADC) have been demonstrated in the epileptogenic zone by using diffusion-weighted magnetic resonance (MR)imaging (DWI). Effects of flumazenil on an epileptogenic focus have been demonstrated by EEG recordings, but not by functional MRI. We hypothesized that dynamic spatiotemporal alterations of brain diffusion of the epileptogenic focus after application of flumazenil will be detectable by DWI and correlate with the epileptogenic zone., Methods: Twelve adult patients considered for epilepsy surgery with medically intractable temporal lobe epilepsy (TLE; n = 7), extratemporal lobe epilepsy (ETE; n = 2), and TLE+ETE (n = 3) were prospectively examined with DWI interictally (serving as baseline) and 10 min after application of 1 mg flumazenil i.v., Results: The baseline interictal ADC was significantly elevated in the hippocampus on the ictogenic side in the patients with TLE (p = 0.002) as compared with healthy volunteers. The following changes of the mean ADC were seen in different regions of interest (ROIs) after injection of flumazenil: decreases in the hippocampus on the seizure-onset side by 14.8% (p = 0.005); decreases in the parahippocampal gyrus on both sides by 6.8% (epileptogenic side; p = 0.044) or 7.9% (nonepileptogenic side; NS), respectively; decreases in the cortex on the nonictogenic side by 7.9% (p = 0.047); and no significant changes of the ADC in the other ROIs., Conclusions: ADC decreases measured after application of flumazenil were seen in the seizure-onset zone as revealed by EEG and structural MRI and are an indicator of focus localization in patients with TLE.

Purpose: Diffusion-weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone., Methods: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2-210 min after a seizure., Results: The interictal ADC was significantly (p < 0.05) elevated in the ictogenic hippocampus in all patients with temporal lobe epilepsy. The following postictal changes of the ADC were seen: (a) decreases by maximally 25-31%, which were most pronounced in the epileptogenic zone (n = 2); (b) generalized ADC changes after generalized seizures (n = 1) or prolonged complex partial seizures (n = 2); (c) no major changes after short-lived seizures or if the time to first DWI scan was >15 min or both (n = 3); and (d) widespread bilateral ADC increases after a flumazenil-induced seizure (n = 1)., Conclusions: ADC changes seen during serial postictal DWI are complex and appear to reflect origin and spread of the preceding seizure. A delineation of the epileptogenic zone appears to be possible only in complex-partial seizures of >60 s duration that do not secondarily generalize.

Background and Purpose: The purpose of this study was to analyse in detail the functional outcome and the neuropsychological deficits in patients with space-occupying infarction of the non-dominant hemisphere one year after surgery., Methods: Postoperative complications and retrospective consent to surgery were assessed in a semi-structured interview in 26 patients. Functional outcome was measured with the Barthel-Index (BI) and Rankin-Scale. Neuropsychological tests in 14 patients focused on visuo-spatial and visuo-constructive abilities, attention, spatial span and self-rated mood., Results: The one-year survival rate was 69 % (18 of 26). The functional outcome was good (BI >/= 90) in 3 patients, fairly good (BI 75-85) in 6, moderate (BI 30-70) in 6, and poor (BI 0-25) in 3 patients. Age was an independent predictor of outcome, patients above 52 years had a BI of 50 or below. Neuropsychological tests (14 of 18) showed profound attention deficits in all patients, and visuo-spatial and visuo-constructive deficits in patients with lower formal education. Retrospectively, 4 of 18 patients would not give consent to surgery again, mostly because of the bad quality of life postoperatively., Conclusion: Older patients do not seem to benefit from decompressive hemicraniectomy; more than half of the surviving younger patients have a good outcome and live independently. Attention deficits are prominent in all patients; visuo-spatial and constructive deficits are less pronounced in patients with higher formal education. Retrospective agreement to decompressive hemicraniectomy is high in patients with good functional outcome.

Hyperventilation (HV) can be used to provoke epileptiform activity and occasionally seizures in generalised and in focal epilepsies. Based on the hypothesis that HV might alter brain diffusion in the epileptogenic areas of patients with temporal lobe epilepsy (TLE), we examined these alterations using quantitative diffusion MR imaging (DI) in four patients with TLE and unilateral hippocampal sclerosis (TLE-HS) and six patients with TLE without hippocampal sclerosis (TLE-pure), and in 10 healthy volunteers. Brain diffusion was measured at baseline and immediately after 4 min of HV. In all patients with TLE HV was repeated two times, 4 min each, followed by subsequent DI. The apparent diffusion coefficient (ADC) was quantified in predefined regions of interest. In controls, the ADC did not differ between baseline and HV and between right and left side. Compared to controls TLE-HS patients showed significantly higher ADC at baseline in the hippocampus of the ictogenic side (111+/-13 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.029). During HV ADC decreased significantly in the ictogenic hippocampus compared to controls (-17.3+/-7.1 vs. -3.34+/-8.7, P=0.004). In TLE-pure patients ADC of the ictogenic hippocampus was higher than in normals (99.3+/-14.2 vs. 87.5+/-4.26 x 10(-5) mm(2)/s, P=0.031) but there was no significant decrease during HV. Serial HV did not further enhance this decrease. No significant HV-induced changes were seen in other brain areas. In conclusion, our results show that HV can induce dynamic changes of brain diffusion in patients with sclerotic hippocampi but not in non-sclerotic hippocampi. These findings may be utilized for lateralisation of the epileptogenic hippocampus during presurgical evaluation of TLE.

We analyzed the clinical course and neuroradiological findings of ten patients aged 27-46 years, with ischemic stroke secondary to vertebral artery dissection (VAD; n = 8) or internal carotid artery dissection (CAD; n = 2), all following chiropractic manipulation of the cervical spine. The following observations were made: (a) All patients had uneventful medical histories, no or only mild vascular risk factors, and no predisposing vascular lesions. (b) VAD was unilateral in five patients and bilateral in three. VAD was located close to the atlantoaxial joint in all eight patients and showed additional involvement of lower sections in six, as well as temporary occlusion of one vertebral artery in three. (c) Nine of ten patients had brain infarction documented by magnetic resonance imaging or computed tomography. (d) Onset of symptoms was immediately after the manipulation (n = 5) or within 2 days (n = 5). (e) Progression of neurological deficits occurred within the following hours to a maximum of 3 weeks. (f) Maximum neurological deficits were severe in nine of ten patients. (g) Outcome after 4 weeks-3 years included no or mild neurological deficits in five patients, marked deficits in three, persistent locked-in syndrome in one, and persistent vegetative state in one. (h) Informed consent was obtained in only one of ten patients. Thus, patients at risk for stroke after chiropractic manipulation may not be identified a priori. Neurological deficits may be severely disabling and are potentially life threatening.

Secondary prevention of transient or permanent cerebral ischemia is performed with antiplatelet drugs, e.g. aspirin, ticlopidine, clopidogrel or dipyridamole. The four substances have different indications and different side effect profiles. Patients with proven or suspected cardiac source of embolism are treated with anticoagulants. Patients with > 70% stenosis of the internal carotid artery and TIA or minor stroke receive carotid endarterectomy in combination with aspirin. Stroke risk is reduced between 20 and 65% by these measures.

Epidemiology focuses on frequency and distribution of diseases and their relevant risk factors. Epidemiologic data are the basis for development of therapeutic strategies, evaluation of prevention and rehabilitation. Stroke in terms of epidemiology includes ischemic brain infarction as well as intracerebral and subarachnoidal hemorrhage. Stroke is most prominent in the elderly with an annual incidence of about 3%. Stroke prevalence varies between 5 and 8%. The 1-year case fatality is about 42%. The mortality rate varies considerably between 20 and 80 per 100 000 in comparable populations in Europe. Hypertension, smoking and atrial fibrillation are the most prominent risk factors; diabetes and the elevated serum cholesterol also contribute.

Twenty-six patients diagnosed as having seasonal affective disorder (SAD) completed weekly depression self-ratings for at least 2.5 and up to 8.25 years. Seasonal recurrence of depression persisted in nine patients, seven remitted, four were chronically depressed, and six showed a diffuse pattern. The age at SAD onset and duration of SAD history before entry into this prospective study could not be identified as predictors of the subsequent course of the disease. Short-lasting, recurrent periods of depression could be identified in many of the long-term records. They were found primarily in autumn and winter in patients with either a persistent seasonal or a remitted pattern. In the core group of patients with persistent seasonal pattern, the onset and offset of depressive periods (DPs) were more variable than the DSM-III-R 60-day window criterion for seasonal pattern allows.

We studied 2 groups of ischemic stroke patients who received therapeutic heparinization during the acute phase in order to prevent thromboembolic reinfarction. 530 patients were studied retrospectively (Group B) and 127 prospectively (Group A). Doses of 24,000-38,000 IE/24 h of heparin were given i.v., resulting in a partial thromboplastin time 2-3 times that of normal controls. Three patients from Group A suffered a massive intracranial hemorrhage. All of them had a large infarction (greater than 5 cm in diameter). They had been given anticoagulants within the first 12 h. Two of them presented with uncontrollable hypertension (systolic BP up to 240 mm Hg). Ischemic reinfarction during the first two weeks occurred in 2.3% and 2.4% of subgroups, respectively. This was less than would have been expected from the literature (approx. 14-15%). Features of these patients were 1.) insufficient heparin dosage, 2.) progression of hemodynamically relevant internal carotid artery lesions leading to critical low-flow or 3.) embolization of a floating thrombus from the internal carotid artery in the middle cerebral artery. It appears that therapeutic heparinization reduces the rate of reinfarction within the acute phase of ischemic strokes. This type of treatment should, however, be confined to patients with an embolic stroke mechanism. Careful surveillance of blood pressure and PTT are prerequisites. Anticoagulation should be avoided in patients with massive infarctions (greater than 5 cm in diameter) or uncontrollable hypertension.

The use of microwave energy for the rapid drying of yeasts is described. The influences of the microwave energy and of the sample thickness are studied. The advantages of the method over the conventional drying techniques are presented.