Diagnosing refractory epilepsy: response to sequential treatment schedules

Diagnosing refractory epilepsy would facilitate referral for specialist pharmacological review and early consideration of epilepsy surgery. An outcomes study was undertaken in an unselected cohort of newly diagnosed patients to determine the number of antiepileptic drug (AED) regimens needed to be failed before the epilepsy could be designated as pharmacoresistant. Between July 1982 and May 2001, 780 adolescents and adults prescribed their first AED at the Western Infirmary in Glasgow, Scotland provided longitudinal data suitable for analysis. Overall, 504 (64.6%) patients became seizure free for at least 12 months. Of these, 462 (59.2%) remained in remission, while 42 (5.4%) relapsed and subsequently developed refractory epilepsy. The relapse rate peaked at 10.4% after 8 years of follow-up. The other 276 (35.4%) patients were uncontrolled from the outset. Prognosis appeared better in seniors (85% remission, P < 0.001) and adolescents (65% remission, P < 0.01) than in the remainder of the population (55% remission). Overall response rates with the first, second and third treatment schedules were 50.4, 10.7 and 2.7%, respectively, with only 0.8% patients responding optimally to further drug trials. Patients not tolerating at least one AED schedule did better than those failing because of lack of efficacy. These data suggest that suitable patients failing two AED regimens should be referred for epilepsy surgery. Those who do not attain long-term seizure freedom with the first three treatment schedules are likely to have refractory epilepsy.     

Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear‐specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non‐refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting‐state functional magnetic resonance imaging (MRI) in patients with refractory and non‐refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed‐to‐voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non‐refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non‐refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting‐state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.     

难治性癫(癎)的发病机制研究进展及前景展望

癫(癎)是儿童常见的神经系统疾病,近年来有关难治性癫(癎)发病机制的研究取得一些突破性进展.文章就难治性癫(癎)发病机制的研究现状进行综述,主要包括4个方面的内容,其中多药转运体表达增多可能导致进入脑组织的药物浓度降低是产生耐药的主要因素,文章重点阐述多药耐药基因和难治性癫(癎)的关系,并对难治性癫(癎)的进一步研究方向和临床应用前景提出新的思路.     

Epilepsy research: a window onto function to and dysfunction of the human brain

As one of the most common neurological disorders, epilepsy has devastating behavioral, social, and occupational consequences and is associated with accumulating brain damage and neurological deficits. Epilepsy comprises a large number of syndromes, which vary greatly with respect to their etiology and clinical features, but share the characteristic clinical hallmark of epilepsy-recurrent spontaneous seizures. Research aimed at understanding the genetic, molecular, and cellular basis of epilepsy has to integrate various research approaches and techniques ranging from clinical expertise, functional analyses of the system and cellular levels, both in human subjects and rodent models of epilepsy, to human and mouse genetics. This knowledge may then be developed into novel treatment options with better control of seizures and/or fewer side effects. In addition, the study of epilepsy has frequently shed light on basic mechanisms underlying the function and dysfunction of the human brain,     

Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force

Despite progress in the development of anti-seizure medications (ASMs), one third of people with epilepsy have drug-resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.