Best practice guidelines for the management of women with epilepsy. The Women with Epilepsy Guidelines Development Group.

Clinical guidelines for the treatment of epilepsy have been published. A statement on management issues for women with epilepsy has recently been produced by the American Academy of Neurology which has raised awareness of the issues facing women with epilepsy. The communication presented here aims to review current literature on specific issues relating to women with epilepsy, and proposes graded recommendations for its management within a UK health care framework.     

SCN1A testing for epilepsy: Application in clinical practice

This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage‐gated sodium channels (protein name: Na_v1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI because genetic confirmation of the clinical diagnosis may allow optimization of antiepileptic therapy with the potential to improve seizure control and developmental outcome. In addition, a molecular diagnosis may prevent the need for unnecessary investigations, as well as inform genetic counseling. (2) SCN1A testing should be considered in people with possible DS where the typical initial presentation is of a developmentally normal infant presenting with recurrent, febrile or afebrile prolonged, hemiclonic seizures or generalized status epilepticus. After age 2, the clinical diagnosis of DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA sequencing of the coding regions and analyses to detect genomic rearrangements within the relevant chromosomal region: 2q24. Interpretation of the test results must always be done in the context of the electroclinical syndrome and often requires the assistance of a medical geneticist, since many genomic variations are possible and it is essential to differentiate benign polymorphisms from pathogenic mutations. (2) Missense variants may have no apparent effect on the phenotype (benign polymorphisms) or may represent mutations underlying DS, MPSI, GEFS+, and related syndromes and can provide a challenge in interpretation. (3) Conventional methods do not detect variations in introns or promoter or regulatory regions; therefore, a negative test does not exclude a pathogenic role of SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A may be involved. Obtaining written informed consent and genetic counseling should be considered prior to molecular testing, depending on the clinical situation and local regulations.     

Application of the 2001 diagnostic scheme and the 2006 ILAE report of seizure and epilepsy: a feedback from the clinical practice of adult epilepsy

Purpose. To clarify the clinical validity and feasibility of the diagnostic scheme for seizures and epilepsy proposed by the International League Against Epilepsy (ILAE) in 2001 (the 2001 Scheme) and the report of the ILAE classification core group in 2006 (the 2006 Report). Methods. One hundred consecutive patients with epilepsy who visited the Neurology Clinic (Group 1) and 100 patients with intractable epilepsy who had undergone prolonged scalp video-EEG monitoring (Group 2) in Kyoto University Hospital were enrolled. The 2001 Scheme (Axis 1 to 4) and the 2006 Report (seizure types and epileptic syndromes) were applied to Group 1. Axis 1 was applied to Group 2 to evaluate the diversity of seizure semiology. Results. Group 1 demonstrated 145 seizures of different types (generalized tonic-clonic seizures: 23%, complex partial seizures (CPS): 29%, simple partial seizures: 21% and secondarily generalized tonic-clonic seizures: 21% according to the 1981 classification. In Axis 1 (ictal phenomenology) of the 2001 scheme, 184 and 333 items were listed in Groups 1 and 2, respectively, and seizure semiology was described independent of EEG findings. However, there was duplications or discordance among the items. In Axis 2 (seizure types) of Group 1, 62% and 26% of CPS were further labeled as focal motor or sensory seizures, respectively; the remainder (24%) did not meet inclusion criteria for any category. In Axis 3 (epilepsy syndromes), 94% of patients were sorted, and familial temporal lobe epilepsy was added. Axis 4 described detailed etiology. Application of seizure types of the 2006 Report required consideration of ictal phenomenology to determine spread patterns. Epileptic syndromes of the 2006 Report were assignable to 70% of patients. Conclusions. It is important to achieve intra- and inter-axial accordance for the establishment of a more practical diagnostic scheme, which may provide a more useful tool for the diagnosis of less obvious aspects of epilepsy.     

Epilepsy,seizures, physical exercise,and sports: A report from the ILAE Task Force on Sports and Epilepsy

People with epilepsy (PWEs) are often advised against participating in sports and exercise, mostly because of fear, overprotection, and ignorance about the specific benefits and risks associated with such activities. Available evidence suggests that physical exercise and active participation in sports may favorably affect seizure control, in addition to producing broader health and psychosocial benefits. This consensus paper prepared by the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy offers general guidance concerning participation of PWEs in sport activities, and provides suggestions on the issuance of medical fitness certificates related to involvement in different sports. Sports are divided into three categories based on potential risk of injury or death should a seizure occur: group 1, sports with no significant additional risk; group 2, sports with moderate risk to PWEs, but no risk to bystanders; and group 3, sports with major risk. Factors to be considered when advising whether a PWE can participate in specific activities include the type of sport, the probability of a seizure occurring, the type and severity of the seizures, seizure precipitating factors, the usual timing of seizure occurrence, and the person's attitude in accepting some level of risk. The Task Force on Sports and Epilepsy considers this document as a work in progress to be updated as additional data become available.     

EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force

Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence‐based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were searched, and original papers, meta‐analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus. Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non‐invasive positive‐pressure ventilation also improves survival and quality of life. Maintaining the patient’s ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end‐of‐life care should be discussed early with the patient and carers, respecting the patient’s social and cultural background.     

Clinical practice guidelines for the treatment of schizophrenia: from theory to practice

INTRODUCTION: Based on the concept of evidence-based medicine (EBM), the clinical practice guidelines (CPG) occupy an increasingly important place in the field of the treatment of schizophrenia. Although CPGs have been elaborated in a rigorous way, few of them provide the readers with tools for their use in practice. The clinician must therefore create his own method of application. This problem was encountered within the framework of a retrospective study carried out in a rehabilitation unit, where we sought to answer the question concerning the use of the CPG approach in the pharmacological treatment of schizophrenia: "to what degree do doctors, with only indirect knowledge, respect these CPGs?" METHOD: The comparative study between CPG and practical current clinic implied: (1) the choice of a pertinent CPG for the clinical framework studied, (2) the selection of measuring instruments, which allow the quantification of obvious clinical problems approached in the CPG, and (3) the development of a standardized system of comparison to determine the degree of respect of the recommendations. The Expert Consensus Guideline for the treatment of schizophrenia (ECGTS) was selected as the reference. A method of application of the ECGTS is depicted: use of standardized clinical scales; translation of the results of the clinical examination in terms of clinical problems to which the recommendations of the guideline refers; and determination of the degree of respect of the recommendations. RESULTS: In the group of 20 patients included in this study, the recommendations of the ECGTS were totally respected in 65% of the patients, and partially respected in 10%, while in 25% of the patients, they were not respected. COMMENTS: These observations suggest that the clinical approach has to be improved, mainly with regard to the treatment of psychotic and depressive symptoms. This work also showed the limits of the CPG: for example, over half of the patients presented side effects on clinical evaluation, whereas the regulation of their medication respected the recommendations of the ECGTS. CONCLUSION: The future certainly belongs to CPG, which proposes, in addition to the clinical recommendations themselves, a method to check their application in clinical practice.     

Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low–middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.     

Treatment of restless legs syndrome: An evidence‐based review and implications for clinical practice

Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence‐based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse events. All studies were classed according to three levels of evidence. All Level‐I trials were included in the efficacy tables; if no Level‐I trials were available then Level‐II trials were included or, in the absence of Level‐II trials, Level‐III studies or case series were included. Only studies published in print or online before December 31, 2006 were included. All studies published after 1996, which attempted to assess RLS augmentation, were reviewed in a separate section. The following drugs are considered efficacious for the treatment of RLS: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Drugs considered likely efficacious are rotigotine, bromocriptine, oxycodone, carbamazepine, valproic acid, and clonidine. Drugs that are considered investigational are dihydroergocriptine, lisuride, methadone, tramadol, clonazepam, zolpidem, amantadine, and topiramate. Magnesium, folic acid, and exercise are also considered to be investigational. Sumanirole is nonefficacious. Intravenous iron dextran is likely efficacious for the treatment of RLS secondary to end‐stage renal disease and investigational in RLS subjects with normal renal function. The efficacy of oral iron is considered investigational; however, its efficacy appears to depend on the iron status of subjects. Cabergoline and pergolide (and possibly lisuride) require special monitoring due to fibrotic complications including cardiac valvulopathy. Special monitoring is required for several other medications based on clinical concerns: opioids (including, but not limited to, oxycodone, methadone and tramadol), due to possible addiction and respiratory depression, and some anticonvulsants (particularly, carbamazepine and valproic acid), due to systemic toxicities. © 2008 Movement Disorder Society     

ICD coding for epilepsy: Past,present, and future—A report by the International League Against Epilepsy Task Force on ICD codes in epilepsy

The World Health Organization (WHO) International Classification of Diseases (ICD) has been used to classify causes of morbidity and mortality such as epilepsy for more than 50 years. The aims of this critical commentary are to do the following: (1) Introduce the ICD classification, summarize the ICD‐9 and ICD‐10 codes for epilepsy and seizures, and discuss the challenges of mapping epilepsy codes between these two versions; (2) discuss how the ICD‐9 and ICD‐10 relate to the revised International League Against Epilepsy (ILAE) terminology and concepts for classification of seizures and epilepsies; (3) discuss how ICD‐coded data have been used for epilepsy care and research and briefly examine the potential impact of the international ICD‐10 clinical modifications on research; (4) discuss the upcoming ICD‐11 codes and the role of the epilepsy community in their development; and (5) discuss how the ICD‐11 will conform more closely to the current ILAE terminology and classification of the epilepsies and seizures and its potential impact on clinical care, surveillance, and public health and research.     

International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods

Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.     

Guidelines for the use of EEG methodology in the diagnosis of epilepsy. International League Against Epilepsy: commission report. Commission on European Affairs: Subcommission on European Guidelines

The Commission of European Affairs of the International League Against Epilepsy published 'Appropriate Standards for Epilepsy Care Across Europe' which contained recommendations for the use of electroencephalography (EEG) in the diagnosis of epilepsy (Brodie et al. Epilepsia 1997; 38:1245). The need for a more specific basic document of EEG methodology was recognized and the Subcommission on European Affairs was asked to produce more detailed guidelines to be used across Europe recognizing the range of practices in EEG laboratories. There are many general guidelines published on EEG methodology but this document focuses on the diagnosis of epilepsy. Details from previously published guidelines are included in references and in an appendix. These guidelines are not meant to be used as minimal standards but recommendations that can be applied to all EEG laboratories despite variations in equipment.     

International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods

Epilepsy surgery is an effective treatment in many patients with drug‐resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)—visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5‐mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery.     

Roadmap for a competency‐based educational curriculum in epileptology: report of the Epilepsy Education Task Force of the International League Against Epilepsy

Teaching competency in the diagnosis and clinical management of epilepsy is of utmost importance for the ILAE. To achieve this mission, the Task Force for Epilepsy Education (EpiEd) developed a competency‐based curriculum for epileptology, covering the spectrum of skills and knowledge for best medical practice. The curriculum encompasses seven domains, 42 competencies, and 124 learning objectives, divided into three levels: entry (Level 1), proficiency (Level 2), and advanced proficiency (Level 3). A survey of the currently existing ILAE‐endorsed teaching activities identified a significant gap in education of basic knowledge of epileptology (Level 1). To bridge this gap, a web‐based educational tool is being developed. A virtual campus will be constructed around the curriculum, integrating the various educational activities of the ILAE. This paper describes the development of the curriculum and future tasks necessary to achieve the educational goal of the ILAE.     

Treatment of restless legs syndrome: Evidence‐based review and implications for clinical practice (Revised 2017)§

The objective of the current review was to update the previous evidence‐based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious. Intravenous ferric carboxymaltose and pneumatic compression devices are considered likely efficacious in idiopathic restless legs syndrome. Bupropion and clonidine were reviewed, but the lack of data determined a rating of insufficient evidence for efficacy. The following interventions continue to be considered efficacious as in 2008: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Bromocriptine, oxycodone, carbamazepine, and valproic acid are considered likely efficacious. Oral iron is nonefficacious in iron‐sufficient subjects, but its benefit for patients with low peripheral iron status has not been adequately evaluated. Restless legs syndrome augmentation has been identified as a significant long‐term treatment complication for pramipexole more than pregabalin and possibly for all dopaminergic agents more than α2δ ligands. Therefore, special monitoring for augmentation is required for all dopaminergic medications as well as tramadol. Other drugs also require special safety monitoring: cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid. Finally, we also highlighted gaps and needs for future clinical research and studies of restless legs syndrome. © 2018 International Parkinson and Movement Disorder Society     

Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the International League Against Epilepsy Neuroimaging Task Force

Structural magnetic resonance imaging (MRI) is of fundamental importance to the diagnosis and treatment of epilepsy, particularly when surgery is being considered. Despite previous recommendations and guidelines, practices for the use of MRI are variable worldwide and may not harness the full potential of recent technological advances for the benefit of people with epilepsy. The International League Against Epilepsy Diagnostic Methods Commission has thus charged the 2013‐2017 Neuroimaging Task Force to develop a set of recommendations addressing the following questions: (1) Who should have an MRI? (2) What are the minimum requirements for an MRI epilepsy protocol? (3) How should magnetic resonance (MR) images be evaluated? (4) How to optimize lesion detection? These recommendations target clinicians in established epilepsy centers and neurologists in general/district hospitals. They endorse routine structural imaging in new onset generalized and focal epilepsy alike and describe the range of situations when detailed assessment is indicated. The Neuroimaging Task Force identified a set of sequences, with three‐dimensional acquisitions at its core, the harmonized neuroimaging of epilepsy structural sequences—HARNESS‐MRI protocol. As these sequences are available on most MR scanners, the HARNESS‐MRI protocol is generalizable, regardless of the clinical setting and country. The Neuroimaging Task Force also endorses the use of computer‐aided image postprocessing methods to provide an objective account of an individual's brain anatomy and pathology. By discussing the breadth and depth of scope of MRI, this report emphasizes the unique role of this noninvasive investigation in the care of people with epilepsy.     

Rufinamide for the treatment of Lennox‐Gastaut syndrome: evidence from clinical trials and clinical practice

Rufinamide was granted orphan drug status in 2004 for the adjunctive treatment of seizures associated with Lennox‐Gastaut syndrome in patients aged ≥4 years, and was subsequently approved for this indication in several countries, including Europe and the United States. Structurally unrelated to other antiepileptic drugs, rufinamide is thought to act primarily by prolonging the inactivation phase of voltage‐gated sodium channels. Rufinamide was approved on the basis of an international, randomised, placebo‐controlled Phase III trial, conducted in 138 patients with Lennox‐Gastaut syndrome, which demonstrated its favourable tolerability profile and efficacy in significantly reducing the frequency of drop attacks and total seizures, compared with placebo. The effectiveness and safety/tolerability of rufinamide in treating seizures associated with Lennox‐Gastaut syndrome have subsequently been confirmed in several other clinical trials and long‐term extension studies. These findings are supported by ‘real‐world’ data from a series of clinical practice studies conducted in Europe, the United States, and Korea. Rufinamide has been shown to be effective and generally well tolerated in children as young as one year and in adults. It is particularly effective as treatment for drop attacks and generalised tonic‐clonic seizures, and it has been suggested that it might be preferred over other antiepileptic drugs as a second‐line treatment for Lennox‐Gastaut syndrome when drop attacks are frequent. The most common side effects of rufinamide treatment include somnolence, headache, dizziness, nausea, vomiting, and fatigue. No new or unexpected safety signals have emerged following long‐term treatment with rufinamide, either in clinical trials or in clinical practice.