Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy.
Epilepsia. 1993 Jul-Aug;34(4):592-6.
Abstract/Text
Ettore Beghi, Arturo Carpio, Lars Forsgren, Dale C Hesdorffer, Kristina Malmgren, Josemir W Sander, Torbjorn Tomson, W Allen Hauser
Recommendation for a definition of acute symptomatic seizure.
Epilepsia. 2010 Apr;51(4):671-5. doi: 10.1111/j.1528-1167.2009.02285.x. Epub 2009 Sep 3.
Abstract/Text
PURPOSE: To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies.
METHODS: Systematic review of the literature and of epidemiologic studies.
RESULTS: An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs.
DISCUSSION: Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
A Krumholz, S Wiebe, G Gronseth, S Shinnar, P Levisohn, T Ting, J Hopp, P Shafer, H Morris, L Seiden, G Barkley, J French, Quality Standards Subcommittee of the American Academy of Neurology, American Epilepsy Society
Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.
Neurology. 2007 Nov 20;69(21):1996-2007. doi: 10.1212/01.wnl.0000285084.93652.43.
Abstract/Text
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
RECOMMENDATIONS: 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).
日本臨床神経生理学会 臨床脳波検査基準改訂委員会: 改訂臨床脳波検査基準2002. 臨床神経生理学 2003; 31: 221-242.
Demetrios Velis, Perrine Plouin, Jean Gotman, Fernando Lopes da Silva, ILAE DMC Subcommittee on Neurophysiology
Recommendations regarding the requirements and applications for long-term recordings in epilepsy.
Epilepsia. 2007 Feb;48(2):379-84. doi: 10.1111/j.1528-1167.2007.00920.x.
Abstract/Text
The purpose of this paper is to update the state of knowledge with respect to long-term monitoring (LTM) in epilepsy and to formulate recommendations regarding the application of LTM in clinical practice. LTM is an established technique in use both in a hospital setting and, increasingly, in an ambulatory and more recently in a community-based setting. There has been sufficient evidence to substantiate the claim that LTM is of crucial importance in documenting electroclinical correlations both in epilepsy and in paroxysmally occurring behavioral changes often mistaken for epilepsy. Internationally recognized neurophysiological equipment standards, data acquisition and data transfer protocols and widely accepted safety standards have made widespread access to LTM facilities in epilepsy possible. Recommendations on efficient and effective use of resources as well as regarding training and competencies for personnel involved in LTM in epilepsy have been formulated. The DMC Neurophysiology Subcommittee of the ILAE recommends use of hospital-based LTM in the documentation of seizures including its application for assessing seizure type and frequency, in the evaluation of status epilepticus, in noninvasive and invasive video/EEG investigations for epilepsy surgery and for the differential diagnosis between epilepsy and paroxysmally occurring nonepileptic conditions, in children and in adults. Ambulatory outpatient and community-based LTM may be used as a substitute for inpatient LTM in cases where the latter is not cost-effective or feasible or when activation procedures aimed at increasing seizure yield are not indicated. However, outpatient ambulatory monitoring may be less informative than is inpatient monitoring in some cases because: (1) reduction of medication to provoke seizures may not be safe as an outpatient; (2) faulty electrode contacts cannot quickly be noticed and repaired; (3) the patient may move out of video surveillance; and (4) duration of ambulatory monitoring can be limited by technical constraints.
日本神経学会監修：てんかん診療ガイドライン2018追補版．2021. Available from: https://www.neurology-jp.org/guidelinem/tenkan_tuiho_2018.html
W A Hauser, S S Rich, J R Lee, J F Annegers, V E Anderson
Risk of recurrent seizures after two unprovoked seizures.
N Engl J Med. 1998 Feb 12;338(7):429-34. doi: 10.1056/NEJM199802123380704.
Abstract/Text
BACKGROUND: Patients with a single unprovoked seizure have about a 35 percent risk of recurrence in the subsequent five years. We studied the risk of recurrence after two unprovoked seizures.
METHODS: We prospectively followed 204 patients with a first unprovoked seizure from the day of the initial seizure. Information was obtained from patients (and verified by a review of their medical records) about the dates and circumstances of any subsequent seizures. The risk of a second, third, and fourth seizure was estimated by the Kaplan-Meier method.
RESULTS: Of the 204 patients, 63 had a second seizure, 41 a third seizure, and 26 a fourth seizure. The mean age of the patients was 36 years, 10 percent were less than 16 years of age, 70 percent were male, 71 percent had epilepsy of unknown cause, and 66 percent had generalized seizures. The risk of a second unprovoked seizure was 33 percent. Among those with a second seizure, the risk of a third unprovoked seizure was 73 percent; among those with a third unprovoked seizure, the risk of a fourth was 76 percent. Most recurrences occurred within one year of the second or third seizure. The risk of a third seizure was higher in those with a presumed cause of epilepsy (relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.4).
CONCLUSIONS: Although only about one third of patients with a first unprovoked seizure will have further seizures within five years, about three quarters of those with two or three unprovoked seizures have further seizures within four years.
A Marson, A Jacoby, A Johnson, L Kim, C Gamble, D Chadwick, Medical Research Council MESS Study Group
Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial.
Lancet. 2005 Jun 11-17;365(9476):2007-13. doi: 10.1016/S0140-6736(05)66694-9.
Abstract/Text
BACKGROUND: The relative risks and benefits of starting or withholding antiepileptic drug treatment in patients with few or infrequent seizures are unclear. We sought to compare policies of immediate versus deferred treatment in such patients and to assess the effects of these policies on short-term recurrence and long-term outcomes.
METHODS: We undertook an unmasked, multicentre, randomised study of immediate and deferred antiepileptic drug treatment in 1847 patients with single seizures and early epilepsy. Outcomes comprised time to first, second, and fifth seizures; time to 2-year remission; no seizures between years 1 and 3 and between years 3 and 5 after randomisation; and quality of life. Analysis was by intention to treat.
FINDINGS: 404 patients invited to join the trial did not consent to randomisation; 722 were subsequently assigned immediate treatment with antiepileptic drugs and 721 were assigned deferred treatment. Immediate treatment increased time to first seizure (hazard ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2-year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in the immediate treatment group and 77% of those in the deferred treatment group were seizure free between 3 and 5 years after randomisation (difference -0.2% [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality of life outcomes or serious complications.
INTERPRETATION: Immediate antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2 years, but does not affect long-term remission in individuals with single or infrequent seizures.
David M Labiner, Anto I Bagic, Susan T Herman, Nathan B Fountain, Thaddeus S Walczak, Robert J Gumnit, National Association of Epilepsy Centers
Essential services, personnel, and facilities in specialized epilepsy centers--revised 2010 guidelines.
Epilepsia. 2010 Nov;51(11):2322-33. doi: 10.1111/j.1528-1167.2010.02648.x.
Abstract/Text
This document was developed by the members of the Committee to Revise the Guidelines for Services, Personnel, and Facilities at Specialized Epilepsy Centers. After discussions with the general membership they were adopted by the Board of the National Association of Epilepsy Centers. The Guidelines will be reviewed and updated when considered necessary by the Board.
L Couldridge, S Kendall, A March
A systematic overview--a decade of research'. The information and counselling needs of people with epilepsy.
Seizure. 2001 Dec;10(8):605-14. doi: 10.1053/seiz.2001.0652.
Abstract/Text
This paper explores the background to epilepsy in terms of medical impact and psychosocial effects. The argument that information and counselling may be central to the person with epilepsy is explored. The evidence from primary research published between 1990 and 2000 investigating the information and counselling needs of people with epilepsy is appraised and synthesized. This paper seeks to answer the following questions: What are the information and counselling needs of people with epilepsy? What are the preferred formats, timing and delivery of information and counselling? What are the outcomes of information giving and counselling for people with epilepsy? The review suggests that there are unmet needs for personal and general information about epilepsy which may include individual or group education and counselling. Information related to gaining control for people with epilepsy and targeted public education may contribute to improved quality of life for people with epilepsy. Information is required which is individually relevant and could be delivered in small groups or as part of an individual counselling service. Specialist epilepsy clinics and specialist nurses can improve patient knowledge and communication and provide an effective and high quality service for people with epilepsy.
Copyright 2001 BEA Trading Ltd.
Philip N Patsalos, David J Berry, Blaise F D Bourgeois, James C Cloyd, Tracy A Glauser, Svein I Johannessen, Ilo E Leppik, Torbjörn Tomson, Emilio Perucca
Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies.
Epilepsia. 2008 Jul;49(7):1239-76. doi: 10.1111/j.1528-1167.2008.01561.x.
Abstract/Text
Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.
山本吉章：治療薬の薬理と薬学管理上の注意点．薬局 2021; 72 (4): 643-52.
Lawrence J Hirsch, Nicolas Gaspard, Andreas van Baalen, Rima Nabbout, Sophie Demeret, Tobias Loddenkemper, Vincent Navarro, Nicola Specchio, Lieven Lagae, Andrea O Rossetti, Sara Hocker, Teneille E Gofton, Nicholas S Abend, Emily J Gilmore, Cecil Hahn, Houman Khosravani, Felix Rosenow, Eugen Trinka
Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.
Epilepsia. 2018 Apr;59(4):739-744. doi: 10.1111/epi.14016. Epub 2018 Feb 5.
Abstract/Text
We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.
Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
日本小児神経学会 監、小児けいれん重積治療ガイドライン策定ワーキンググループ 編：小児けいれん重積治療ガイドライン2017．診断と治療社、2017 https://www.childneuro.jp/modules/about/index.php?content_id=36.
G Jannuzzi, P Cian, C Fattore, G Gatti, A Bartoli, F Monaco, E Perucca
A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.
Epilepsia. 2000 Feb;41(2):222-30.
Abstract/Text
PURPOSE: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.
METHODS: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.
RESULTS: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.
CONCLUSIONS: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.
Patrick Kwan, Alexis Arzimanoglou, Anne T Berg, Martin J Brodie, W Allen Hauser, Gary Mathern, Solomon L Moshé, Emilio Perucca, Samuel Wiebe, Jacqueline French
Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.
Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3.
Abstract/Text
To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
神一敬：SUDEP―最近の話題．Epilepsy. 2021;15(1):15-20.
赤松直樹：COVID-19流行期におけるてんかん診療の注意点と，COVID-19 のてんかん診療への影響について．Epilespy.2020;14:105-9.
