Effect of vagus nerve stimulation against generalized seizure and status epilepticus recurrence

ObjectiveVagus nerve stimulation (VNS) is a palliative surgery for drug-resistant epilepsy. The two objectives of this study were to (1) determine the seizure type most responsive to VNS and (2) investigate the preventive effect on status epilepticus (SE) recurrence.MethodsWe retrospectively reviewed 136 patients with drug-resistant epilepsy who underwent VNS implantation. We examined seizure outcomes at 6, 12, and 24 months following implantation of VNS as well as at the last visit to the Juntendo Epilepsy Center. Univariate analysis and multivariate logistic regression models were used to estimate the prognostic factors.Results125 patients were followed up for at least 1 year after VNS implantation. The percentage of patients with at least a 50% reduction in seizure frequency compared with prior to VNS implantation increased over time at 6, 12, and 24 months after VNS implantation: 28, 41, and 52%, respectively. Regarding overall seizure outcomes, 70 (56%) patients responded to VNS. Of the 40 patients with a history of SE prior to VNS implantation, 27 (67%) showed no recurrence of SE. The duration of epilepsy, history of SE prior to VNS implantation and seizure type were correlated with seizure outcomes after VNS implantation in univariate analysis (p = 0.05, p < 0.01, and p = 0.03, respectively). In multivariate logistic regression analysis, generalized seizure was associated with VNS response [odds ratio (OR): 4.18, 95% CI: 1.13–15.5, p = 0.03]. A history of SE prior to VNS implantation was associated with VNS non-responders [(OR): 0.221, 95% CI: 0.097–0.503, p < 0.01]. The duration of epilepsy, focal to bilateral tonic–clonic seizure and epileptic spasms were not significantly associated with VNS responders (p = 0.07, p = 0.71, and p = 0.11, respectively).ConclusionFollowing 125 patients with drug-resistant epilepsy for an average of 69 months, 56% showed at least 50% reduction in seizure frequency after VNS implantation. This study suggests that generalized seizure is the most responsive to VNS, and that VNS may reduce the risk of recurrence of SE. VNS was shown to be effective against generalized seizure and also may potentially influence the risk of further events of SE, two marker of disease treatment that can lead to improved quality of life

Reconciling biodiversity conservation and flood risk reduction : The new strategy for freshwater protected areas

Aim: Natural disaster risk reduction (DRR) is becoming a more important function of protected area (PAs) for current and future global warming. However, biodiversity conservation and DRR have been handled separately and their interrelationship has not been explicitly addressed. This is mainly because, due of prevailing strategies and criteria for PA placement, a large proportion of PAs are currently located far from human-occupied areas, and habitats in human-occupied areas have been largely ignored as potential sites for conservation despite their high biodiversity. If intensely developed lowland areas with high flooding risk overlap with important sites for biodiversity conservation, it would be reasonable to try to harmonize biodiversity conservation and human development in human-inhabited lowland areas. Here, we examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and whether human-inhabited lowland flood risk management sites might be suitable to designate as freshwater protected areas (FPAs). Location: Across Japan. Methods: We examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and analysed the relationship between candidate sites for new FPAs and flood disaster risk and land use intensity at a national scale across Japan based on distribution data for 131 freshwater fish species and 1395 macroinvertebrate species. Results: We found that extant PAs overlapped with approximately 30% of conservation-priority grid cells (1 km2) for both taxa. Particularly for red-listed species, only one species of freshwater fish and three species of macroinvertebrate achieved the representation target within extant PAs. Moreover, more than 40% of candidate conservation-priority grid cells were located in flood risk and human-occupied areas for both taxa. Main conclusions: Floodplain conservation provides suitable habitat for many freshwater organisms and helps control floodwaters, so establishing new FPAs in areas with high flood risk could be a win-win strategy for conserving freshwater biodiversity and enhancing ecosystem-based DRR (eco-DRR)

Germination of photoblastic lettuce seeds is regulated via the control of endogenous physiologically active gibberellin content, rather than of gibberellin responsiveness

Phytochrome regulates lettuce (Lactuca sativa L. cv. Grand Rapids) seed germination via the control of the endogenous level of bioactive gibberellin (GA). In addition to the previously identified LsGA20ox1, LsGA20ox2, LsGA3ox1, LsGA3ox2, LsGA2ox1, and LsGA2ox2, five cDNAs were isolated from lettuce seeds: LsCPS, LsKS, LsKO1, LsKO2, and LsKAO. Using an Escherichia coli expression system and functional assays, it is shown that LsCPS and LsKS encode ent-copalyl diphosphate synthase and ent-kaurene synthase, respectively. Using a Pichia pastoris system, it was found that LsKO1 and LsKO2 encode ent-kaurene oxidases and LsKAO encodes ent-kaurenoic acid oxidase. A comprehensive expression analysis of GA metabolism genes using the quantitative reverse transcription polymerase chain reaction suggested that transcripts of LsGA3ox1 and LsGA3ox2, both of which encode GA 3-oxidase for GA activation, were primarily expressed in the hypocotyl end of lettuce seeds, were expressed at much lower levels than the other genes tested, and were potently up-regulated by phytochrome. Furthermore, LsDELLA1 and LsDELLA2 cDNAs that encode DELLA proteins, which act as negative regulators in the GA signalling pathway, were isolated from lettuce seeds. The transcript levels of these two genes were little affected by light. Lettuce seeds in which de novo GA biosynthesis was suppressed responded almost identically to exogenously applied GA, irrespective of the light conditions, suggesting that GA responsiveness is not significantly affected by light in lettuce seeds. It is proposed that lettuce seed germination is regulated mainly via the control of the endogenous content of bioactive GA, rather than the control of GA responsiveness

Prognostic Determinants of Anterior Large Vessel Occlusion in Acute Stroke in Elderly Patients

This study investigated prognostic factors in elderly patients (80 years and older) undergoing mechanical thrombectomy (MT) for anterior circulation large vessel occlusion (LVO) in acute stroke treatment. Of 59 cases, 47.5% achieved a favorable outcome (mRS ≤ 3) at three months, with a mortality rate of 20.3%. Factors associated with better outcomes included younger age, lower admission National Institute of Health Stroke Scale (NIHSS) scores, lower N-terminal pro-brain natriuretic peptide (NT-proBNP) and D-dimer levels, the presence of the first pass effect (FPE), and successful recanalization. However, logistic regression showed that only lower admission NIHSS scores were significantly correlated with favorable outcomes. In addition, this study suggests that lower admission NT-proBNP and D-dimer levels could potentially serve as prognostic indicators for elderly LVO patients undergoing MT

Splicing of human chloride channel 1

Expression of chloride channel 1 (CLCN1/ClC-1) in skeletal muscle is driven by alternative splicing, a process regulated in part by RNA-binding protein families MBNL and CELF. Aberrant splicing of CLCN1 produces many mRNAs, which were translated into inactive proteins, resulting in myotonia in myotonic dystrophy (DM), a genetic disorder caused by the expansion of a CTG or CCTG repeat. This increase in abnormal splicing variants containing exons 6B, 7A or the insertion of a TAG stop codon just before exon 7 leads to a decrease in expression of the normal splice pattern. The majority of studies examining splicing in CLCN1 have been performed using mouse Clcn1, as have investigations into the activation and suppression of normal splicing variant expression by MBNL1-3 and CELF3–6, respectively. In contrast, examinations of human CLCN1 have been less common due to the greater complexity of splicing patterns. Here, we constructed a minigene containing CLCN1 exons 5–7 and established a novel assay system to quantify the expression of the normal splicing variant of CLCN1 using real-time RT-PCR. Antisense oligonucleotides could promote normal CLCN1 alternative splicing but the effective sequence was different from that of Clcn1. This result differs from previous reports using Clcn1, highlighting the effect of differences in splicing patterns between mice and humans

Statistical Features in High-Frequency Bands of Interictal iEEG Work Efficiently in Identifying the Seizure Onset Zone in Patients with Focal Epilepsy

The design of a computer-aided system for identifying the seizure onset zone (SOZ) from interictal and ictal electroencephalograms (EEGs) is desired by epileptologists. This study aims to introduce the statistical features of high-frequency components (HFCs) in interictal intracranial electroencephalograms (iEEGs) to identify the possible seizure onset zone (SOZ) channels. It is known that the activity of HFCs in interictal iEEGs, including ripple and fast ripple bands, is associated with epileptic seizures. This paper proposes to decompose multi-channel interictal iEEG signals into a number of subbands. For every 20 s segment, twelve features are computed from each subband. A mutual information (MI)-based method with grid search was applied to select the most prominent bands and features. A gradient-boosting decision tree-based algorithm called LightGBM was used to score each segment of the channels and these were averaged together to achieve a final score for each channel. The possible SOZ channels were localized based on the higher value channels. The experimental results with eleven epilepsy patients were tested to observe the efficiency of the proposed design compared to the state-of-the-art methods

Dynamic tractography- based localization of spike sources and animation of spike propagations

ObjectiveThis study was undertaken to build and validate a novel dynamic tractography- based model for localizing interictal spike sources and visualizing monosynaptic spike propagations through the white matter.MethodsThis cross- sectional study investigated 1900 spike events recorded in 19 patients with drug- resistant temporal lobe epilepsy (TLE) who underwent extraoperative intracranial electroencephalography (iEEG) and resective surgery. Twelve patients had mesial TLE (mTLE) without a magnetic resonance imaging- visible mass lesion. The remaining seven had a mass lesion in the temporal lobe neocortex. We identified the leading and lagging sites, defined as those initially and subsequently (but within - ¤50 ms) showing spike- related augmentation of broadband iEEG activity. In each patient, we estimated the sources of 100 spike discharges using the latencies at given electrode sites and diffusion- weighted imaging- based streamline length measures. We determined whether the spatial relationship between the estimated spike sources and resection was associated with postoperative seizure outcomes. We generated videos presenting the spatiotemporal change of spike- related fiber activation sites by estimating the propagation velocity using the streamline length and spike latency measures.ResultsThe spike propagation velocity from the source was 1.03 mm/ms on average (95% confidence interval = .91- 1.15) across 133 tracts noted in the 19 patients. The estimated spike sources in mTLE patients with International League Against Epilepsy Class 1 outcome were more likely to be in the resected area (83.9% vs. 72.3%, Ï Â = .137, p < .001) and in the medial temporal lobe region (80.5% vs. 72.5%, Ï Â = .090, p = .002) than those associated with the Class - ¥2 outcomes. The resulting video successfully animated spike propagations, which were confined within the temporal lobe in mTLE but involved extratemporal lobe areas in lesional TLE.SignificanceWe have, for the first time, provided dynamic tractography visualizing the spatiotemporal profiles of rapid propagations of interictal spikes through the white matter. Dynamic tractography has the potential to serve as a unique epilepsy biomarker.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170234/1/epi17025_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170234/2/epi17025.pd

Classification of the Epileptic Seizure Onset Zone Based on Partial Annotation.

Epilepsy is a chronic disorder caused by excessive electrical discharges. Currently, clinical experts identify the seizure onset zone (SOZ) channel through visual judgment based on long-time intracranial electroencephalogram (iEEG), which is a very time-consuming, difficult and experience-based task. Therefore, there is a need for high-accuracy diagnostic aids to reduce the workload of clinical experts. In this article, we propose a method in which, the iEEG is split into the 20-s segment and for each patient, we ask clinical experts to label a part of the data, which is used to train a model and classify the remaining iEEG data. In recent years, machine learning methods have been successfully applied to solve some medical problems. Filtering, entropy and short-time Fourier transform (STFT) are used for extracting features. We compare them to wavelet transform (WT), empirical mode decomposition (EMD) and other traditional methods with the aim of obtaining the best possible discriminating features. Finally, we look for their medical interpretation, which is important for clinical experts. We achieve high-performance results for SOZ and non-SOZ data classification by using the labeled iEEG data and support vector machine (SVM), fully connected neural network (FCNN) and convolutional neural network (CNN) as classification models. In addition, we introduce the positive unlabeled (PU) learning to further reduce the workload of clinical experts. By using PU learning, we can learn a binary classifier with a small amount of labeled data and a large amount of unlabeled data. This can greatly reduce the amount and difficulty of annotation work by clinical experts. All together, we show that using 105 minutes of labeled data we achieve a classification result of 91.46% on average for multiple patients