941 resultados para Generalized Epilepsy
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We report two patients with microdeletions in chromosomal subdomain 15q26.1 encompassing only two genes, CHD2 and RGMA. Both patients present a distinct phenotype with intellectual disability, epilepsy, behavioral issues, truncal obesity, scoliosis and facial dysmorphism. CHD2 haploinsufficiency is known to cause intellectual disability and epilepsy, RGMA haploinsufficiency might explain truncal obesity with onset around puberty observed in our two patients.
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OBJECTIVE There is increasing evidence that epileptic activity involves widespread brain networks rather than single sources and that these networks contribute to interictal brain dysfunction. We investigated the fast-varying behavior of epileptic networks during interictal spikes in right and left temporal lobe epilepsy (RTLE and LTLE) at a whole-brain scale using directed connectivity. METHODS In 16 patients, 8 with LTLE and 8 with RTLE, we estimated the electrical source activity in 82 cortical regions of interest (ROIs) using high-density electroencephalography (EEG), individual head models, and a distributed linear inverse solution. A multivariate, time-varying, and frequency-resolved Granger-causal modeling (weighted Partial Directed Coherence) was applied to the source signal of all ROIs. A nonparametric statistical test assessed differences between spike and baseline epochs. Connectivity results between RTLE and LTLE were compared between RTLE and LTLE and with neuropsychological impairments. RESULTS Ipsilateral anterior temporal structures were identified as key drivers for both groups, concordant with the epileptogenic zone estimated invasively. We observed an increase in outflow from the key driver already before the spike. There were also important temporal and extratemporal ipsilateral drivers in both conditions, and contralateral only in RTLE. A different network pattern between LTLE and RTLE was found: in RTLE there was a much more prominent ipsilateral to contralateral pattern than in LTLE. Half of the RTLE patients but none of the LTLE patients had neuropsychological deficits consistent with contralateral temporal lobe dysfunction, suggesting a relationship between connectivity changes and cognitive deficits. SIGNIFICANCE The different patterns of time-varying connectivity in LTLE and RTLE suggest that they are not symmetrical entities, in line with our neuropsychological results. The highest outflow region was concordant with invasive validation of the epileptogenic zone. This enhanced characterization of dynamic connectivity patterns could better explain cognitive deficits and help the management of epilepsy surgery candidates.
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Eight surface observation sites providing quasi-continuous measurements of atmospheric methane mixingratios have been operated since the mid-2000’s in Siberia. For the first time in a single work, we assimilate 1 year of these in situ observations in an atmospheric inversion. Our objective is to quantify methane surface fluxes from anthropogenic and wetland sources at the mesoscale in the Siberian lowlands for the year 2010. To do so, we first inquire about the way the inversion uses the observations and the way the fluxes are constrained by the observation sites. As atmospheric inver- sions at the mesoscale suffer from mis-quantified sources of uncertainties, we follow recent innovations in inversion techniques and use a new inversion approach which quantifies the uncertainties more objectively than the previous inversion systems. We find that, due to errors in the representation of the atmospheric transport and redundant pieces of information, only one observation every few days is found valuable by the inversion. The remaining high-resolution quasi-continuous signal is representative of very local emission patterns difficult to analyse with a mesoscale system. An analysis of the use of information by the inversion also reveals that the observation sites constrain methane emissions within a radius of 500 km. More observation sites than the ones currently in operation are then necessary to constrain the whole Siberian lowlands. Still, the fluxes within the constrained areas are quantified with objectified uncertainties. Finally, the tolerance intervals for posterior methane fluxes are of roughly 20 % (resp. 50 %) of the fluxes for anthropogenic (resp. wetland) sources. About 50–70 % of Siberian lowlands emissions are constrained by the inversion on average on an annual basis. Extrapolating the figures on the constrained areas to the whole Siberian lowlands, we find a regional methane budget of 5–28 TgCH4 for the year 2010, i.e. 1–5 % of the global methane emissions. As very few in situ observations are available in the region of interest, observations of methane total columns from the Greenhouse Gas Observing SATellite (GOSAT) are tentatively used for the evaluation of the inversion results, but they exhibit only a marginal signal from the fluxes within the region of interest.
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INTRODUCTION This report from the World Psychiatric Association Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviors in patients with epilepsy. MATERIALS AND METHODS A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the Food and Drug Administration (FDA) report on the increase risk for patients under antiepileptics to manifest suicidality is also included in this report. RESULTS The analysis of these studies revealed that the data are not supportive of the presence of a "class effect" on suicide-related behavior; on the contrary, there are some data suggesting such an effect concerning treatment with topiramate, lamotrigine, and levetiracetam for which further research is needed. DISCUSSION For the majority of people with epilepsy, anticonvulsant treatment is necessary and its failure for any reason is expected to have deleterious consequences. Therefore, clinicians should inform patients and their families of this increased risk of suicidal ideation and behavior, but should not overemphasize the issue. Specific subgroups of patients with epilepsy might be at a higher risk, and deserve closer monitoring and follow-up. Future research with antiepileptics should specifically focus on depression and suicidal thoughts.
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OBJECTIVE To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients. RESULTS We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features. CONCLUSION De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.
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BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF. KEYWORDS: Cognitive behavioral therapy; Evidence-based treatment; Implementation strategies; Randomized controlled trial
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Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC-SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. (©) RSNA, 2016 Online supplemental material is available for this article.
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OBJECTIVE In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger-causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.
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Determining the profit maximizing input-output bundle of a firm requires data on prices. This paper shows how endogenously determined shadow prices can be used in place of actual prices to obtain the optimal input-output bundle where the firm.s shadow profit is maximized. This approach amounts to an application of the Weak Axiom of Profit Maximization (WAPM) formulated by Varian (1984) based on shadow prices rather than actual prices. At these prices the shadow profit of a firm is zero. Thus, the maximum profit that could have been attained at some other input-output bundle is a measure of the inefficiency of the firm. Because the benchmark input-output bundle is always an observed bundle from the data, it can be determined without having to solve any elaborate programming problem. An empirical application to U.S. airlines data illustrates the proposed methodology.
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We propose a nonparametric model for global cost minimization as a framework for optimal allocation of a firm's output target across multiple locations, taking account of differences in input prices and technologies across locations. This should be useful for firms planning production sites within a country and for foreign direct investment decisions by multi-national firms. Two illustrative examples are included. The first example considers the production location decision of a manufacturing firm across a number of adjacent states of the US. In the other example, we consider the optimal allocation of US and Canadian automobile manufacturers across the two countries.
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With the recognition of the importance of evidence-based medicine, there is an emerging need for methods to systematically synthesize available data. Specifically, methods to provide accurate estimates of test characteristics for diagnostic tests are needed to help physicians make better clinical decisions. To provide more flexible approaches for meta-analysis of diagnostic tests, we developed three Bayesian generalized linear models. Two of these models, a bivariate normal and a binomial model, analyzed pairs of sensitivity and specificity values while incorporating the correlation between these two outcome variables. Noninformative independent uniform priors were used for the variance of sensitivity, specificity and correlation. We also applied an inverse Wishart prior to check the sensitivity of the results. The third model was a multinomial model where the test results were modeled as multinomial random variables. All three models can include specific imaging techniques as covariates in order to compare performance. Vague normal priors were assigned to the coefficients of the covariates. The computations were carried out using the 'Bayesian inference using Gibbs sampling' implementation of Markov chain Monte Carlo techniques. We investigated the properties of the three proposed models through extensive simulation studies. We also applied these models to a previously published meta-analysis dataset on cervical cancer as well as to an unpublished melanoma dataset. In general, our findings show that the point estimates of sensitivity and specificity were consistent among Bayesian and frequentist bivariate normal and binomial models. However, in the simulation studies, the estimates of the correlation coefficient from Bayesian bivariate models are not as good as those obtained from frequentist estimation regardless of which prior distribution was used for the covariance matrix. The Bayesian multinomial model consistently underestimated the sensitivity and specificity regardless of the sample size and correlation coefficient. In conclusion, the Bayesian bivariate binomial model provides the most flexible framework for future applications because of its following strengths: (1) it facilitates direct comparison between different tests; (2) it captures the variability in both sensitivity and specificity simultaneously as well as the intercorrelation between the two; and (3) it can be directly applied to sparse data without ad hoc correction. ^
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It is well recognized that offspring of women with epilepsy who are taking anticonvulsant medications have an increased incidence of clefting abnormalities. This increase has been attributed to the teratogenic effects of anticonvulsant medications but an alternative explanation involving a genetic association of epilepsy and clefting has also been proposed. Five family studies attempting to resolve this controversy have been inconclusive either because of study design or analytic limitations. This family study was designed to determine whether epilepsy aggregates in families ascertained by an individual with a clefting disorder. The Mayo Clinic medical linkage registry was used to identify individuals with cleft lip with or without cleft palate and cleft palate in southeast Minnesota from 1935-1986. Only those cases who were 15 years or younger during this period were included in the study. The proband's parents and descendants of their parents, including the proband's sibs, children, grandchildren, niece/nephews, grandnieces/nephews, halfsibs and spouses were also identified and all of their medical records were reviewed for seizure disorders. The standardized morbidity ratios for epilepsy of 0.9 (95% CI 0.2-2.6) observed for first degree relatives (excluding parents) and 0.0 for second degree relatives were not increased. The SMRs ranged from 0.7-2.2 for the individual relative types (parents 1.5, sibs 0.7, children 2.2, probands 1.1, spouses 2.0) and were also not increased. These results do not support the suggestions of some that clefting and epilepsy aggregate together in families. ^
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The extent to which antiepileptic drugs (AED) in utero exposure are related to prenatal and postnatal growth is investigated in an retrospective, cohort study of children of AED treated mothers with epilepsy (N = 89) and children of women without epilepsy (N = 89). The study groups were obtained from a population based health care facility.^ Major finding was that birth head circumference of AED exposed children are significantly smaller than control children, notably male children. Other findings include birth length and weight of exposed children was slightly but not significantly smaller. Postnatal growth as measured by two velocity terms, rate of growth, and deceleration, was not significantly different between exposed and control children for height, weight, and head circumference, indicating no catch up growth. Morphologic defects, neonatal and infant mortality was more frequent in exposed children. Mothers with epilepsy reported significantly fewer spontaneous abortions. ^
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Epilepsy is a very complex disease which can have a variety of etiologies, co-morbidities, and a long list of psychosocial factors4. Clinical management of epilepsy patients typically includes serological tests, EEG's, and imaging studies to determine the single best antiepileptic drug (AED). Self-management is a vital component of achieving optimal health when living with a chronic disease. For patients with epilepsy self-management includes any necessary actions to control seizures and cope with any subsequent effects of the condition9; including aspects of treatment, seizure, and lifestyle. The use of computer-based applications can allow for more effective use of clinic visits and ultimately enhance the patient-provider relationship through focused discussion of determinants affecting self-management. ^ The purpose of this study is to conduct a systematic literature review on informatics application in epilepsy self-management in an effort to describe current evidence for informatics applications and decision support as an adjunct to successful clinical management of epilepsy. Each publication was analyzed for the type of study design utilized. ^ A total of 68 publications were included and categorized by the study design used, development stage, and clinical domain. Descriptive study designs comprised of three-fourths of the publications and indicate an underwhelming use of prospective studies. The vast majority of prospective studies also focused on clinician use to increase knowledge in treating patients with epilepsy. ^ Due to the chronic nature of epilepsy and the difficulty that both clinicians and patients can experience in managing epilepsy, more prospective studies are needed to evaluate applications that can effectively increase management activities. Within the last two decades of epilepsy research, management studies have employed the use of biomedical informatics applications. While the use of computer applications to manage epilepsy has increased, more progress is needed.^