Lack of Evidence Complicates Care for Nursing Home Residents With Epilepsy

Guidelines and epilepsy practice: Antiseizure medication initiation following an unprovoked first seizure in adults

Recently, a practical clinical definition has been proposed by the International League Against Epilepsy(ILAE). Management of an unprovoked first seizure in adults has also been reported with risk factors of recurrence relevant to epilepsy diagnosis by the American Academy of Neurology. The term "unprovoked" implies the absence of a temporary or reversible factor lowering the threshold and producing a seizure at that point in time. A seizure immediately after a stroke or head injury would exemplify a provoked seizure, as called acute symptomatic(or early)seizure, that would not lead to a diagnosis of epilepsy. The underlying mechanisms that cause the early seizure are considered to be different from those of epileptogenesis associated with recurrent epileptic seizures. Psychogenic non-epileptic seizure(PNES)or syncope resembles epileptic seizures and are often misdiagnosed. Some clinical features can help distinguish PNES or syncope from epileptic seizure. Clinicians should be familiarized with seizure semiology presumable to epilepsy. The incidence of epilepsy increases steadily after 50 years of age. As in younger people, the diagnosis of epilepsy is a clinical decision; however, in older people this can be more challenging. Many disorders, common in older people may confuse epilepsy seizures which should be differentiated by appropriate investigations.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Lawrence J. HirschLawrence J. HirschLawrence J. Hirsch, MD is Professor of Neurology, Chief of the Division of Epilepsy and EEG, and Co-Director of the Comprehensive Epilepsy Center, all at Yale University, USA. He has held leadership positions in the American Clinical Neurophysiology Society (ACNS), American Epilepsy Society, American Academy of Neurology, and the Epilepsy Foundation, and is lead author of the 2012 and 2021 ACNS guidelines on critical care EEG terminology. He is founder and former chair of the Critical Care EEG Monitoring Research Consortium, which now includes more than 50 centers, and co-chair of the medical advisory board of the NORSE Institute. He has been an active researcher throughout his career, having published more than 200 peer-reviewed manuscripts and more than 100 reviews, editorials or book chapters on topics including status epilepticus, all aspects of EEG including intracranial recordings and brain monitoring in the critically ill, brain stimulation, epilepsy surgery, seizure clusters, rescue medications, sudden death in epilepsy (SUDEP), and anti-seizure medication use. He has won multiple teaching awards and is co-author of the first-ever atlas on EEG in critical care, now in its 2nd edition. He continues to see patients in the inpatient and outpatient setting, direct fellowship programs, teach, mentor, and manage a large epilepsy division at a level IV Comprehensive Epilepsy Center. Michael F. WatersMichael F. WatersMichael F. Waters, MD, PhD, is a neurologist, director of both the Neurovascular Division and the Petznick Stroke Center, and a professor in the Department of Neurology at Barrow Neurological Institute, USA. He is board certified in neurology by the American Board of Psychiatry and Neurology with subspecialty board certification in vascular neurology. Dr Waters’ expertise is stroke and neurovascular disease, including signs, symptoms, diagnostics, and treatments. He is a fellow of both the American Academy of Neurology and American Heart Association and a member of the American Neurological Association, American Society of Human Genetics, and the Society of Vascular and Interventional Neurology. Dr Waters received his Masters in genetics from Penn State University in State College, Pennsylvania, USA, and his doctorate in biochemistry and molecular biology from The University of Florida College of Medicine in Gainesville, USA, where he also completed his MD. He completed his residency training at the University of California – Los Angeles Department of Neurology and completed his fellowship in clinical and molecular neurogenetics at Cedars Sinai Medical Center in Los Angeles, USA. Dr Waters’ research studies include genetic mechanisms of stroke, neuroprotection in stroke, stroke treatment, multiple clinical trials investigating stroke treatments, and neurogenetic mechanisms of neuroplasticity.

In July 2009, the International League against Epilepsy (ILAE) developed its four-year strategic plan in collaboration with past, current, and future leaders (www.ilae-epilepsy.org). This is the first yearly progress report, prepared by the management committee and the chair of the Strategic Task Force, to highlight progress toward achieving the plan’s goals.

Suicide, Epilepsy-Drug Link Becomes a Little Clearer

ILAE President's midterm report

In July 2009, the International League Against Epilepsy (ILAE) developed its 4-year strategic plan. This is the second-year progress report, prepared by the management committee and the chair of the Strategic Task Force, with input from several key leaders, to highlight progress toward achieving the plan’s goals. Additional information regarding our activities can be found at our renovated website (http://www.ilae-epilepsy.org). As the major international epilepsy organization, ILAE is taking the lead in developing practice guidelines for clinical questions faced by clinicians who are managing people with epilepsy. A new Task Force on Guidelines, chaired by Tim Pedley, has been appointed. The aims are the following: to compile and review existing epilepsy guidelines; to identify those guidelines that can be adopted worldwide or in specific parts of the world; to assess the needs of the League’s chapters around the world; to identify the most important areas for new guideline development; and to determine whether a topic or question is best served by a formal clinical practice guideline (which may be hindered by the paucity of methodologically rigorous evidence) or by a position paper that represents the consensus of experts supported by the available evidence. Because the development of guidelines is time-consuming and expensive, the League may partner in this project with organizations such as the World Federation of Neurology (WFN), the American Academy of Neurology (AAN), and the European Federation of Neurological Societies (EFNS). To succeed, the League will seek the help of many volunteers and provide necessary staff support. The Epidemiology Commission and Marco Medina continue their work with the World Health Organization (WHO) to develop the epilepsy-related codes for the ICD-11. The League’s website has been redesigned. Jean Gotman, our Web and Media Director, and Ed Bertram, our Information Officer, are hiring a Web manager. Each Commission has the responsibility to oversee the content of its section and to create links to ILAE activities, including Long Distance Education and Global Outreach. A Web Editorial Board tasked to provide advice on development and use of the website has been appointed. The new web-based social networking Community Suite (Higher Logic) for ILAE groups is now fully operational. Plans are progressing to provide our Chapters access to ILAE Social Media. The League has made arrangements with Wiley-Blackwell to make Epilepsia available online at no charge to our constituencies in resource-poor countries that belong to the Hinari program. In addition, the League is discussing with Wiley-Blackwell the creation of a sister online journal to accommodate the needs of our constituents, while maintaining a high impact factor for Epilepsia. Plans are underway for appointment of the next Editors-in-Chief. By 2013, Phil Schwartzkroin and Simon Shorvon will have completed 8 years of service in this capacity, which is the maximum allowed by the constitution. We anticipate that the new Editor(s) will be appointed by January 2013 and will begin their tenure with the new Executive in 2013. The 29th International Epilepsy Congress (IEC) was held in Rome August 28th to September 1, 2011. Nearly 4,000 delegates attended this highly successful Congress. Its program aimed at integrating all aspects of epilepsy (including medical, research, social, and novel therapeutic approaches) in each session. A prime example was the Presidential symposium entitled “Avoiding Deaths in Epilepsy,” During the 29th Congress, the International Epilepsy Bureau (IBE) celebrated its 50th anniversary with two exceptional events: A get-together of the Ambassadors of Epilepsy, a highly prestigious honor initially conceived by IBE and now conferred by joint deliberations of the IBE and ILAE Executive Committee every 2 years; and a magnificent concert. Work is ongoing for the preparation of four Regional Congresses scheduled for 2012, including the 9th Asian-Oceanian Epilepsy Congress in Manila (21–25 March 2012), the 10th European Congress of Epileptology in London (30 September–4 October 2012), the Latin American Epilepsy Congress in Quito (14–17 November 2012), and the African Epilepsy Congress in Nairobi (21–23 June 2012). The latter will be the first African Congress organized jointly by the ILAE and the IBE and represents a major component of the educational activities targeted to the African continent by our newly formed Commission on African Affairs. The 30th IEC will be held in Montreal, Canada on June 23–27, 2013. During the 29th International Congress held in Rome, Dr. Jerome Engel Jr. received the Life Achievement Award and Dr. Pravina Shah received the Social Accomplishment Award. Dr. Eleonora Aronica was the Michael Prize winner and Dr. Laura Jansen was the recipient of the Morris-Coole Epilepsia Award. Twelve new Ambassadors for Epilepsy were elected (Table 1). The regional commissions are establishing bi-annual awards that recognize regional accomplishments. The Commission on European Affairs (CEA) established the European Epileptology Award in 2002. The latest awards were bestowed on Drs. Yehezkiel Ben-Ari and Martin Brodie during the 9th European Congress in Rhodes in 2010. The CEA plans to expand the number of awards starting in 2012. During the 2012 London Congress there will be up to two European Research (clinical and basic) Awards for Young investigators: one for Education and one for Service to Europe. The Asian-Oceanian Commission granted their first awards during the 8th Asian Oceanian Epilepsy Congress (AOEC) in 2010. The recipients of the Asian and Oceanian Outstanding Achievement Epilepsy Awards included Drs Hasan Aziz, Tatsuya Tanaka, Kazuichi Yagi, P. Satish Chandra, and Xun Wu. The League solidified the organizational and financial stability of the long-distance education program by acquiring direct supervision of this initiative, and by investing in the expansion of the Virtual Epilepsy Academy (VIREPA) to promote teaching courses under the coordination of regional academies. To this end, the Education Commission through its Task Force on Distance Education, led by Walter van Emde Boas, has instituted approaches to increase the attractiveness and accessibility of ongoing courses, and has added new courses on pediatric epilepsies and electroencephalography (EEG), psychiatric aspects, and sleep and epilepsy. Moreover, plans are underway to organize a course for primary caregivers in Sub-Saharan Africa in collaboration with the Task Force on Seizures and Epilepsy in the Tropics, the African Commission, and the WHO. The Education Commission led by CT Tan is developing ways to make educational material generated during our congresses freely available through the League’s website. This was started with a trial run of voice/power point slides captured during the Melbourne AOEC, and the “How to” education session during Rome IEC. In Rome, through an effort coordinated by our Information Officer, many presenters addressing timely topics were also interviewed to produce videos, which are currently posted on the League’s website. This will be a regular feature of future congresses. The Education Commission is creating an open access, online Textbook of Epilepsy (Shi Hui Lim, Editor), housed at the ILAE website. We expect the first edition to be available in the first quarter of 2012. We plan translations of the textbook into Spanish and Chinese. Congresses are being reorganized to promote translational research venues that allow for better communication between basic scientists and clinicians. The Neurobiology and the Education Commissions are developing proposals for further training of professionals, including a combination of residential courses with hands-on tutoring of research proposals that are likely to impact resource-poor regions favorably. This initiative may include guidance in preparing grant applications, provision of seed grants, and monitoring research progress. The Academies of the Regional Commissions have developed year-round, 1–2 day teaching courses in various parts of the regions. For example, the Asian Epilepsy Academy (ASEPA) organizes about 10 such courses yearly. These courses reach out to diverse populations, address different needs, and are generally more cost-effective than traditional large congresses. The longer and more in depth “summer schools” continue to be organized in Europe and Latin America, and have also been launched in Asia. Other projects by the regional commissions/academies include visiting professorships between the North America and the Caribbean/Latin America; fellowships by the Asian and Latin American Commissions, EEG certification examination, and publication of congress proceedings by ASEPA. Vital partners in basic research collaborations are the International Brain Research Organization (IBRO) and the Society for Neuroscience. An important aim is to identify and publicize possible funding sources for such programs, and to increase public and government awareness of the needs of people with epilepsy. Discussion is underway with the WFN and the International Child Neurology Association (ICNA) to develop collaborative visiting professorships for Africa. The key aim is to create a long-term relationship between institutions. This initiative will involve the Education, North American, and African Commissions. Finally, three commission-related reports were published (Blümcke et al., 2011; Gaillard et al., 2011; Thurman et al., 2011). We continue our Global Campaign efforts together with IBE and WHO. Because several additional initiatives do not fall under the collaborative efforts of the Global Campaign, together with IBE we created the Global Outreach Task Force, chaired by Helen Cross and Shichuo Li with expert assistance from Hanneke de Boer. The primary aim of this task force is to raise awareness of global educational and service initiatives in epilepsy throughout the world. The Task Force has identified a new slogan, initially proposed by Mike Glynn, President of IBE: “Stand up for epilepsy.” The slogan is in the process of being registered. The second SUDEP, A Global Conversation book was launched in Rome 6 years after the first edition, with forewords by the ILAE and IBE Presidents. Much has changed since the earlier edition was launched at the Paris IEC, and almost all of it for the better in relation to epilepsy deaths. However, much remains to be done, especially in the area of prevention and with regard to people at risk of sudden unexpected death in epilepsy (SUDEP) being warned of it together with their loved ones. This book brings together contributions on the subject of SUDEP from all around the world including pieces from many developing countries. ILAE and IBE are engaged in several regional activities to highlight the public health dimensions of the epilepsies, and to prioritize allocation of resources to epilepsy health care and research. These initiatives include the production of an epilepsy report by the U.S. Institute of Medicine (IOM) (http://www.iom.edu/Activities/Disease/Epilepsy.aspx), the finalization of the Pan American Health Organization (PAHO) Strategy for the Americas, (http://new.paho.org/hq/index.php?option=com_content&task=view&id=5272&Itemid=3841&lang=en), and the support for the European Written Declaration on Epilepsy endorsed by the European Parliament (http://www.ilae-epilepsy.org/visitors/initiatives/EuropeanDeclaration.cfm). The IOM report will specifically address the following questions: How can the public health burden of epilepsy for patients and families be more accurately assessed? What priorities for future population health studies could inform treatment and prevention? How can the access to health and human services and the quality of care for people with epilepsy be improved? How can the education and training of professionals who work with people with epilepsy be improved? How can the understanding of epilepsy in patients and the general public be improved to create supportive communities? The report will be released in 2012. The 51st Directing Counseling of the Pan American Health Organization (PAHO; which includes representatives from countries of North, Central, and South America) approved and endorsed the Action Plan on Epilepsy for the Americas on September 29, 2011. The Action Plan was prepared by Dr. Jorge Rodriquez from PAHO and Drs. Carlos Acevedo and Marco Medina as part of the Global Task Force of the ILAE and IBE. The Action Plan highlights the problems associated with epilepsy care throughout the developed and developing countries of the Americas and lists specific goals and anticipated deliverables that would positively impact epilepsy care in the region, with a 10-year focus on epilepsy. In Europe, efforts are ongoing to advocate for political actions in the fight against epilepsy. The executive body of the European Union (EU) is its Commission. The two key Commissioners who can influence health care and research in epilepsy are European Commissioner John Dalli, Commissioner for Health and Consumer Policy, and European Commissioner Máire Geoghegan-Quinn, Commissioner for Research, Innovation and Science. During European Epilepsy Day, both Commissioners held meetings with delegations from IBE and ILAE led by the two Presidents at the European Parliament in Strasbourg. A Joint Task Force of ILAE and IBE, cochaired by Emilio Perucca and Mike Glynn and including members of the ILAE and IBE regional governing bodies (CAE and EREC respectively), has also been established under the name Epilepsy Advocacy Europe (EAE). EAE aims at making epilepsy care and research a priority in the agenda of the European Union (EU) and national governments in the European region. Its first action was to obtain the endorsement of the Written Declaration of Epilepsy by the European Parliament. This was achieved with a majority vote of the European Parliament on September 15, 2011. The Declaration calls for the EU to support research and innovation in the prevention and early diagnosis and treatment of epilepsy; to prioritize epilepsy as a major disease that imposes a significant burden of illness across Europe; to encourage Member States to ensure equal quality of life, including education, employment, transport, and public health care, for people with epilepsy; to encourage effective epilepsy health impact assessments on all major EU and national policies; and to introduce appropriate legislation to protect the rights of all people with epilepsy. The next steps will be to capitalize on the Declaration by ensuring that its recommendations are adopted by the European Commission and by national governments. A European Conference on Epilepsy is being planned with participation of all major stakeholders from the European Commission, the European Council, national governments, funding organizations, lay organizations, and the medical and research community. Our collaborative efforts are beginning to bear fruit. In November, 2010, the Colombian Congress passed a law establishing special measures of protection for people with epilepsy with principles and guidelines that call for comprehensive care of people with epilepsy. Five additional Task Forces have been established: The Seizures and Epilepsy in the Tropics Task Force (chair P. M. Preux), working in close collaboration with the Global Outreach Task Force, aims at addressing issues pertaining to seizures and epilepsy in the tropics, in particular as they relate to etiology, sociocultural aspects, and management. The Stigma Task Force (N. Jetté, chair) with support from the North American Commission, aims at determining ways to combat epilepsy-related stigma and its consequences worldwide. The Task Force on Sports and Epilepsy (G. Capovilla, chair), has two main aims: (1) to seek out and foster opportunities for interactions with major sports authorities and organizations to increase awareness about epilepsy worldwide; and (2) to increase participation of people with epilepsy in sports activities according to their capabilities. The Task Force on Preclinical Drug Discovery (M. Simonato and T. O’Brien, chairs) intends to develop standardized definitions, pathways, techniques, and endpoints for the discovery and preclinical development of new epilepsy treatments, and to enable a stronger evidence base to identify optimal candidates to take forward to clinical development. The Task Force on ILAE Reports (E. Bertram, chair) will develop guiding principles for writing reports generated by the ILAE, standardize processes for their internal and external review, and develop criteria for their designation as official position statements of the League. The Task Force on Sports and Epilepsy is launching an exciting project to create a collection of photographs of famous sports persons meeting people with epilepsy. The photographs will convey the message that people with epilepsy, like athletes themselves, can be inspired to achieve their goals and lead full and active lives. The collection is intended for publication as a book of photographs, and the images will be made available to National Chapters for advocacy initiatives in their own countries. The ILAE’s strategic plan includes a role as the global leader in epilepsy education. To this end, under the leadership of Ed Bertram, the League developed a series of short, patient-oriented videos dealing with common issues faced by patients (what is epilepsy?, symptoms, diagnosis, treatment, surgery, pregnancy, stigma, where to find treatment, causes, and prevention). Although most of the 3-min videos were designed for web use, two shorter videos with a clear concise message will be used for public news broadcasts (pregnancy and living with epilepsy). The League has undertaken a campaign to draw attention to the successes of members of our constituency and the importance of epilepsy. Letters have been written to appropriate authorities (deans and regional and national health ministers) about important contributions made by our colleagues (awards, organization of successful events, publication of important documents, elections to leadership positions, celebrations). Authorities will receive the message that epilepsy-related work provides much positive publicity for their institution or country and that epilepsy is an important health problem. We encourage further interaction with the national chapters in these initiatives. As with any such effort, the results can be slow in appearing and require regular reinforcement, but feedback from some members have suggested that these efforts have resulted in first contacts with health ministers as well as positive responses from deans. During the 29th IEC in Rome, the General Assembly ratified seven new National Chapters (Bolivia, Cameroon, El Salvador, Kosovo, Kuwait, Nigeria, and Sri Lanka), for a total of 108 active chapters. In addition, applications from 14 countries are being processed. The League’s secretariat is revising the rules for chapter incorporation to increase participation. Regional commissions are exploring ways in which isolated clinicians can easily interact with the League in countries and territories where formation of an ILAE Chapter is unfeasible. The new Constitution was ratified by the General Assembly at the 29th International Epilepsy Congress held in Rome on August 31, 2011 and is available on the website (http://www.ilae-epilepsy.org). It ensures that all regions have a voice and a seat in the Executive Committee. In 2013, the League will be electing its new officers. The dates for each step will be communicated to all chapters by the Chair of the elections committee, Past President Peter Wolf. The new Conflict of Interest policy is also available on the website. To enhance communication among commissions and with the leadership, a Commission Chair meeting is held annually. Here, the Regional and Task Oriented Commissions present their work and identify synergies for collaboration. The Commission Chairs will meet again in December 2011 to identify projects congruent with the 2009 ILAE Strategic Plan that can be completed in 2012 and 2013. In addition, the League’s leadership has asked Commissions to include plans to disseminate reports and activities to stakeholders and to implement action items. As discussed in the Year 1 report, steps have been taken to enhance the management of our financial resources and improve transparency in reporting and disclosing financial data. Our Finance Committee and Financial Advisory Subcommittee, which include members of the financial and corporate world, have worked effectively to this end. The most important product of these activities has been the finalization of a new Investment Policy intended to improve returns on the League’s investments while maintaining a conservative approach consistent with the organization’s nonprofit status and goals. One of the goals will be for the League to be able within the next 10 years to derive a sufficient return from investments to support activities at the current level, thereby compensating for a projected loss in revenue from congresses and other sources. The new Investment Policy also recognizes the international scope of our activities by making for in and world To this end, the Executive Committee endorsed the of Finance Committee and Financial Advisory to the management of the League’s to a new Financial with in at the international The of the latter will be according to Finally, the new Investment Policy recognizes of issues by direct investments into that and medical We again the many volunteers who their and toward the League’s strategic aims and to improve the of people with epilepsy throughout the world. We also our in Peter and in close collaboration with the and Glynn under the of International of We the advice and input we received from Ed Bertram, CT Walter Boas, Jean Gotman, Mike Glynn, Hanneke de Phil Simon and Tim in the preparation of this We also Phil Schwartzkroin and Simon Shorvon for has received research support from and the is on the Editorial Board of Neurobiology of Brain and and has received a from and a from received or research from and and research support from the of the for and Research, the and the European Commission of the also in the of Epilepsy Research, in in Drug in and Drug on for Epilepsy and the of Neurological and research support from the for Research and the Brain on the of of Epilepsy Neurology and Epilepsy and on the Committee of and received research support from and We that we have the position on issues in publication and that this report is consistent with those

The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient care based on analysis of evidence. For this practice parameter the authors reviewed available evidence relevant to evaluating adults presenting with an apparent unprovoked first seizure. Relevant questions were defined and addressed by multiple searches of medical literature. Each article was then reviewed, abstracted, and classified using an established evidence scoring system. Conclusions and recommendations were based on a standard three-tiered scheme of evidence classification. For adults presenting with a first seizure, a routine EEG revealed epileptiform abnormalities in approximately 23% of patients, and these were predictive of seizure recurrence. A brain imaging study (CT or MRI) was significantly abnormal in 10% of patients, indicating a possible seizure etiology. Laboratory tests such as blood counts, blood glucose, and electrolyte panels were abnormal in up to 15% of individuals, but abnormalities were minor and did not cause the seizure. Overt clinical signs of infection such as fever typically predicted significant CSF abnormalities on lumbar puncture. Toxicology screening studies were limited, but report some positive tests. EEG should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Brain imaging with CT or MRI should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Laboratory tests, such as blood counts, blood glucose, and electrolyte panels (particularly sodium), lumbar puncture, and toxicology screening may be helpful as determined by the specific clinical circumstances based on the history, physical, and neurologic examination, but there are insufficient data to support or refute recommending any of these tests for the routine evaluation of adults presenting with an apparent first unprovoked seizure (Level U).

To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%-45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (>3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years.

Evidence-based guideline: Management of an unprovoked first seizure in adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. METHODS: We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. RESULTS AND RECOMMENDATIONS: Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%–45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (> 3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk for AED adverse events (AEs) may range from 7%–31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians’ recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years.

Following the occurrence of an unprovoked first seizure in adults, the risk of seizure recurrence is greatest within the next 2 years. Although immediate antiepileptic drug therapy will not improve the longer-term (>3 years) prognosis for seizure remission, it will reduce the risk of seizure recurrence over the first 2 years. An individualized treatment plan that considers the likelihood of seizure recurrence versus the risks of adverse events should be adopted.

Commentary: ILAE definition of Epilepsy.

Eating behavior problems in children with epilepsy (6-16years): A cross-sectional comparative study.

The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization's defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom (no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25%, 50%, or 75% cutoffs for the DDD of each AED. Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p < 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p < 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at <75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08-2.37). Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.