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Managing drug-resistant epilepsy: challenges and solutions
Despite the development of new antiepileptic drugs (AEDs), ~20%-30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy (DRE). This multifaceted condition comprises intractable seizures, neurobiochemical changes, cognitive decline, and psychosocial dysfunction. An ongoing challenge to both researchers and clinicians alike, DRE management is complicated by the heterogeneity among this patient group. The underlying mechanism of DRE is not completely understood. Many hypotheses exist, and relate to both the intrinsic characteristics of the particular epilepsy (associated syndrome/lesion, initial response to AED, and the number and type of seizures prior to diagnosis) and other pharmacological mechanisms of resistance. The four current hypotheses behind pharmacological resistance are the \"transporter\", \"target\", \"network\", and \"intrinsic severity\" hypotheses, and these are reviewed in this paper. Of equal challenge is managing patients with DRE, and this requires a multidisciplinary approach, involving physicians, surgeons, psychiatrists, neuropsychologists, pharmacists, dietitians, and specialist nurses. Attention to comorbid psychiatric and other diseases is paramount, given the higher prevalence in this cohort and associated poorer health outcomes. Treatment options need to consider the economic burden to the patient and the likelihood of AED compliance and tolerability. Most importantly, higher mortality rates, due to comorbidities, suicide, and sudden death, emphasize the importance of seizure control in reducing this risk. Overall, resective surgery offers the best rates of seizure control. It is not an option for all patients, and there is often a significant delay in referring to epilepsy surgery centers. Optimization of AEDs, identification and treatment of comorbidities, patient education to promote adherence to treatment, and avoidance of triggers should be periodically performed until further insights regarding causative pathology can guide better therapies.
Journal Article
الأساليب الحديثة في انتقاء الموظفين : المرجع في استخدام اختبارات القدرات العقلية والشخصية في العمل
جاء هذا الكتاب لكي يقدم للقارئ والخبير والمدير العربي الأساليب الحديثة في انتقاء الموظفين وتحديدا الأساليب التي تعتمد على القياس الدقيق لمهارات وقدرات وكفاءات المتقدمين للوظيفة والمقارنة بينها واختيار أفضلهم بناء على نتائج كمية قابلة للملاحظة والمقارنة. إن المراجعة الدقيقة لواقع أساليب انتقاء الموظفين في الوطن العربي تشير إلى أنه ما زال هناك الاعتماد الكبير على الثالوث الكلاسيكي في الانتقاء وهو : طلب التوظيف، ورسائل التوصية والمقابلة الوظيفية. وقد اكدت الدراسات الحديثة المستفيضة ان هذا الاسلوب قاصر عن اختيار الموظف الكفؤ نظرا لانه مبني على حكم شخصي وذاتي ولا يوجد به الدليل الكمي القاطع. لذلك، يقدم هذا الكتاب أفكار تطبق في العالم الصناعي المتقدم لانتقاء الموظفين والمفاضلة بينهم وتحديد الأساليب التي تعتمد على فكرة القياس السيكومتري للقدرات والمهارات البشرية كأساس للحكم على مدى تمتع الافراد بالمهارات المطلوبة ودرجة صلاحيتهم للوظيفة.
Book
Cycles in epilepsy
Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over diverse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.In this Review, the authors provide an overview of the evidence for daily, multi-day and yearly cycles in epileptic brain activity. They also discuss advances in our understanding of the mechanisms underlying these cycles and the potential clinical applications of this knowledge.
Journal Article
استكشاف الهيدروكربون وإنتاجه
تضم هذه السلسلة ترجمة لأحدث الكتب عن التقنيات التي يحتاج إليها الوطن العربي في البحث والتطوير ونقل المعرفة إلى القارئ العربي. الكتاب، مقدمة شاملة وحديثة للصناعة المتطورة، يربط بين العديد من التخصصات ذات الصلة، ويقدم بالتنقيب والتقييم، لمختلف المراحل في عمر حقل نفط أو غاز، ابتداء من كسب فرصة الدخول أو مرورا على البيئة المالية والتجارية المواكبة لتطوير إيقاف التشغيل، مركزا ثم التخطيط، فالإنتاج، وأخيرا الحقل. يخاطب الكتاب محترفي الصناعة الراغبين بالاطلاع على أفضل الطرائق التقنية والتجارية في مهنة النفط والغاز.
BOOK
Critical slowing down as a biomarker for seizure susceptibility
The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.
Critical slowing (associated with increased variance and autocorrelation) can precede critical state transitions. Here, the authors show critical slowing can be used as a marker in seizure forecasting algorithms.
Journal Article
Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study
Seizure prediction would be clinically useful in patients with epilepsy and could improve safety, increase independence, and allow acute treatment. We did a multicentre clinical feasibility study to assess the safety and efficacy of a long-term implanted seizure advisory system designed to predict seizure likelihood and quantify seizures in adults with drug-resistant focal seizures.
We enrolled patients at three centres in Melbourne, Australia, between March 24, 2010, and June 21, 2011. Eligible patients had between two and 12 disabling partial-onset seizures per month, a lateralised epileptogenic zone, and no history of psychogenic seizures. After devices were surgically implanted, patients entered a data collection phase, during which an algorithm for identification of periods of high, moderate, and low seizure likelihood was established. If the algorithm met performance criteria (ie, sensitivity of high-likelihood warnings greater than 65% and performance better than expected through chance prediction of randomly occurring events), patients then entered an advisory phase and received information about seizure likelihood. The primary endpoint was the number of device-related adverse events at 4 months after implantation. Our secondary endpoints were algorithm performance at the end of the data collection phase, clinical effectiveness (measures of anxiety, depression, seizure severity, and quality of life) 4 months after iniation of the advisory phase, and longer-term adverse events. This trial is registered with ClinicalTrials.gov, number NCT01043406.
We implanted 15 patients with the advisory system. 11 device-related adverse events were noted within four months of implantation, two of which were serious (device migration, seroma); an additional two serious adverse events occurred during the first year after implantation (device-related infection, device site reaction), but were resolved without further complication. The device met enabling criteria in 11 patients upon completion of the data collection phase, with high likelihood performance estimate sensitivities ranging from 65% to 100%. Three patients' algorithms did not meet performance criteria and one patient required device removal because of an adverse event before sufficient training data were acquired. We detected no significant changes in clinical effectiveness measures between baseline and 4 months after implantation.
This study showed that intracranial electroencephalographic monitoring is feasible in ambulatory patients with drug-resistant epilepsy. If these findings are replicated in larger, longer studies, accurate definition of preictal electrical activity might improve understanding of seizure generation and eventually lead to new management strategies.
NeuroVista.
Journal Article
Seizure pathways: A model-based investigation
We present the results of a model inversion algorithm for electrocorticography (ECoG) data recorded during epileptic seizures. The states and parameters of neural mass models were tracked during a total of over 3000 seizures from twelve patients with focal epilepsy. These models provide an estimate of the effective connectivity within intracortical circuits over the time course of seizures. Observing the dynamics of effective connectivity provides insight into mechanisms of seizures. Estimation of patients seizure dynamics revealed: 1) a highly stereotyped pattern of evolution for each patient, 2) distinct sub-groups of onset mechanisms amongst patients, and 3) different offset mechanisms for long and short seizures. Stereotypical dynamics suggest that, once initiated, seizures follow a deterministic path through the parameter space of a neural model. Furthermore, distinct sub-populations of patients were identified based on characteristic motifs in the dynamics at seizure onset. There were also distinct patterns between long and short duration seizures that were related to seizure offset. Understanding how these different patterns of seizure evolution arise may provide new insights into brain function and guide treatment for epilepsy, since specific therapies may have preferential effects on the various parameters that could potentially be individualized. Methods that unite computational models with data provide a powerful means to generate testable hypotheses for further experimental research. This work provides a demonstration that the hidden connectivity parameters of a neural mass model can be dynamically inferred from data. Our results underscore the power of theoretical models to inform epilepsy management. It is our hope that this work guides further efforts to apply computational models to clinical data.
Journal Article