苯巴比妥单药治疗四川省某农村地区癫痫7年效果评价

目的了解苯巴比妥单药治疗农村地区惊厥型癫痫的有效性及安全性。方法对2005年-2012年纳入绵阳市游仙区、三台县农村地区1326例惊厥型癫痫患者,给予苯巴比妥单药治疗,起始剂量为每晚60mg/次。日服用最大剂量不超过210mg/日。观察其疗效、不良反应。结果 49.4%的患者未规律服药,19.4%的患者从未治疗过,仅31.2%的患者接受了正规治疗。86.2%的癫痫患者服用苯巴比妥剂量范围在60~150mg/日。服用苯巴比妥第1年有效率68.2%,长期随访发现有效率在第3年达67.3%,并在以后随访中稳定在63%左右。治疗后4个月存在消化道症状、共济失调不良反应,随服药时间延长不良反应减轻。结论农村地区癫痫诊治缺口巨大,苯巴比妥单药治疗农村地区惊厥型癫痫表现出良好的疗效和安全性,应在农村地区加强癫痫患者诊治管理及相关知识普及。     

Efficacy assessment of phenobarbital in epilepsy: a large community-based intervention trial in rural China

BACKGROUND: Many people with epilepsy need not experience further seizures if the diagnosis and treatment are correct. Most epilepsy patients have convulsions, which are usually fairly easy to diagnose. This study tested a model for treatment of people with convulsive forms of epilepsy at primary health-care level in rural areas of China. METHODS: Patients with convulsive epilepsy were identified at primary care level and provided with phenobarbital monotherapy. Local physicians, who were provided with special training, carried out screening, treatment, and follow-up. A local neurologist confirmed the diagnoses. Efficacy was assessed from the percentage reduction in seizure frequency from baseline and the retention of patients on treatment. FINDINGS: The study enrolled 2455 patients. In 68% of patients who completed 12 months' treatment, seizure frequency was decreased by at least 50%, and a third of patients were seizure free. 72% of patients who completed 24 months' treatment had reduction of seizure frequency of at least 50% and a quarter of patients remained seizure free. Probability of retention was 0.84 at 1 year, and 0.76 at 2 years. Medication was well tolerated and reported adverse events were mild; only 32 patients (1%) discontinued medication because of side-effects. INTERPRETATION: This pragmatic study confirmed that this simple protocol was suitable for the treatment of convulsive forms of epilepsy in rural areas of China. Physicians with basic training could treat epilepsy patients with phenobarbital, with beneficial effects for most patients with convulsive seizures. Few cognitive or behavioural adverse events were noted, but formal psychometric testing was not done.     

Current status of epilepsy treatment and efficacy of standard phenobarbital therapy in rural areas of Northern China

Purpose: To investigate the current status of epilepsy treatment and the efficacy and adverse effects of phenobarbital therapy in rural areas of Northern China. Methods: A total of 2192 patients diagnosed with convulsive epilepsy were recruited from seven different rural regions in Jilin Province, China to investigate the current status of epilepsy treatment, and 1379 of them were enrolled in a standard phenobarbital therapy trial. Patients were selected according to strict inclusion and exclusion criteria, and medical records for all patients were collected and analyzed before the standard treatment was started. Patients were followed up monthly, and efficacy in 1218 patients was analyzed at 1, 3, 6 and 12 months of treatment. Results: More patients had the initial seizure in juveniles than in adults, and 40.72% of the 2192 patients were not receiving any treatment before the treatment trial. The efficacy of phenobarbital increased and adverse effects decreased within the treatment period. Among the 349 patients who were followed up for 12 months from the beginning of the phenobarbital treatment, seizures were decreased by more than 75% in 71.3% of patients using a low-to-medium dose of phenobarbital. Major adverse effects of phenobarbital included mild exhaustion, drowsiness, dizziness and headache. Conclusions: Standardized long-term and regular administration of phenobarbital at a low-to-medium dose can be used as an effective, economic and safe treatment against epilepsy in rural areas.     

The operational model of a network for managing patients with convulsive epilepsy in rural West China

ObjectiveTo establish an operational model of a network for managing patients with convulsive epilepsy in rural areas of West China.MethodsThe network is under unified leadership of the public health administration departments, who liaised with medical institutions and disease control and prevention organizations to foster local communities to participate. Patients with convulsive epilepsy were treated with phenobarbital. Trained local primary health care physicians carried out screening, treatment, and follow-up. Political, financial, and technological support was incrementally provided through the network. Efficacy was assessed as the percentage reduction in seizure frequency and the retention of patients on treatment.ResultsTwo thousand five hundred fourteen patients with active convulsive epilepsy were enrolled. After more than 1 year of treatment, 78.4% of the patients had a 50% or greater reduction in seizure frequency and 43.3% remained seizure free. Probability of retention was 85.8% at 750 days. Nearly 20% patients withdrew from the project, and most of them migrated out of the study areas. Some regular training and educational programs were also carried out.ConclusionThis pragmatic procedure suggests that the network could be suitable for managing convulsive epilepsy in resource-poor regions. Such a network could depend on existing primary health services to ensure its sustainability.     

世界卫生组织-全球抗癫痫运动中国农村癫痫示范项目结束后四年随访结果

目的了解全球抗癫痫运动中国农村抗癫痫示范项目终止后4年曾接受苯巴比妥治疗的癫痫患者的远期治疗效果及转归,以为我国农村癫痫患者的防治和管理提供参考依据。方法2008年7—12月由经过培训的乡卫生院医师采用问卷与访谈相结合的形式入户调查,对原示范项目6省（市）共8个县经苯巴比妥治疗管理的2455例惊厥型癫痫患者进行随访。结果接受苯巴比妥治疗的2455例患者中共随访到1780例,其中939例（52．75％）继续服药,无发作和发作减少超过50％（有效）的患者于项目终止后的12、24、36和48个月时所占比例分别为66．77％（627／939）、68．37％（642／939）、71．35％（670／939）和73．06％（686／939）;841例（47．25％）停药患者中244例（29．01％）无发作、320例（38．05％）仍然发作但已停药、277例（32．94％）改用其他类型抗癫痫药物。对939例继续服用苯巴比妥与841例停药的癫痫患者进行疗效比较,继续服药者的远期疗效优于停药者（x2=12．423,P=0．002）。停药原因分别为发作停止（244例,29．01％）、改用其他抗癫痫药物（277例,32．94％）、未提供免费药物或无钱买药（93例,11．06％）、治疗效果欠佳（92例,10．94％）、当地买不到苯巴比妥（54例,6．42％）等。至2008年随访结束时共有206例患者死亡,标化死亡比达19．10;其中意外事故死亡为59例（28．64％）,其次为脑血管病30例（14．56％）、癫痫持续状态窒息死亡28例（13．59％）。结论“全球抗癫痫运动”中国农村癫痫示范项目开展成功,远期治疗效果良好,值得进一步推广。癫痫人群死亡率高,尤其是意外事故死亡率高,值得引起注意。     

Update on causes of premature death in people with convulsive epilepsy in rural West China

This longitudinal prospective study updated a previous report on premature mortality and focused on the risk factors among patients with convulsive epilepsy in resource‐poor settings. The present cohort size (7,231) and follow‐up (mean 33.4 months) were expanded. The basic epidemiologic aspects of this cohort were similar to the original report (case fatality: 3.26% vs. 2.97%, respectively; injury contributed more than half of the deaths). Cox regression analysis suggested that male patients, late ages of onset (>45 years old), short duration of epilepsy (<10 years), and high convulsive seizure frequency (>2 per month) were independent risk factors for overall premature death. Male patients with late ages of onset and high seizure frequency had a higher risk of injury‐specific death. This study emphasizes the preventable nature of injuries that are leading putative causes of death among people with convulsive epilepsy in rural West China. Education on specific populations and efficient seizure control are of paramount importance in reducing the risk of premature mortality.     

Genomic microdeletions associated with epilepsy: not a contraindication to resective surgery

Purpose: Several recent reports of genomic microdeletions in epilepsy will generate further research; discovery of more microdeletions and other important classes of variants may follow. Detection of such genetic abnormalities in patients being evaluated for surgical treatment might raise concern that a genetic defect, possibly widely expressed in the brain, will affect surgical outcome. Methods: A reevaluation was undertaken of clinical presurgical data, histopathology of surgical specimen, and postsurgical outcome in patients with mesial temporal lobe epilepsy (MTLE) who have had surgical treatment for their drug‐resistant seizures, and who have been found to have particular genomic microdeletions. Key Findings: Three thousand eight hundred twelve patients with epilepsy were genotyped and had a genome‐wide screen to identify copy number variation. Ten patients with MTLE, who had resective epilepsy surgery, were found to have 16p13.11 microdeletions or other microdeletions >1 Mb. On histopathology, eight had classical hippocampal sclerosis (HS), one had nonspecific findings, and one had a hamartoma. Median postsurgical follow‐up time was 48 months (range 10–156 months). All patients with HS were seizure‐free after surgery, International League Against Epilepsy (ILAE) outcome class 1, at last follow‐up; the patient with nonspecific pathology had recurrence of infrequent seizures after 7 years of seizure freedom. The patient with a hamartoma never became seizure‐free. Significance: Large microdeletions can be found in patients with “typical” MTLE. In this small series, patients with MTLE who meet criteria for resective surgery and harbor large microdeletions, at least those we have detected, can have a good postsurgical outcome. Our findings add to the spectrum of causal heterogeneity of MTLE + HS.     

Long‐term health‐related quality of life in drug‐resistant temporal lobe epilepsy after anterior temporal lobectomy

Epilepsy surgery is beneficial to patients suffering from drug‐resistant temporal lobe epilepsy in the short term, but fewer reports of long‐term outcomes have been published. To clarify the long‐term outcomes of seizure control and health‐related quality of life after epilepsy surgery, we enrolled 48 patients suffering from drug‐resistant temporal lobe epilepsy. All of the patients received comprehensive presurgical evaluations, including the Quality of Life in Epilepsy Inventory‐89 (QOLIE‐89) questionnaire to measure their health‐related quality of life. Among the patients, 28 patients received surgery (surgical group) and 20 patients remained under medication (medical group). Eight years later, the seizure frequency and QOLIE‐89 were evaluated. The seizure‐free rate was much higher in the surgical group (53.6%) than in the medical group (5%), eight years after the initial evaluation. The follow‐up QOLIE‐89 score was significantly higher in the surgical group than in the medical group. Moreover, the seizure frequency inversely correlated to the QOLIE‐89 score, regardless of the treatment group. Our results provide evidence that epilepsy surgery confers benefits with respect to seizure control and health‐related quality of life for drug‐resistant temporal lobe epilepsy patients based on long‐term follow‐up.     

A population‐based study of long‐term outcome of epilepsy in childhood with a focal or hemispheric lesion on neuroimaging

Purpose: To evaluate long‐term seizure outcome in children with epilepsy and a focal or hemispheric neuroimaging abnormality. Methods: All children (<18 years and residing in Olmsted County, Minnesota) with new‐onset epilepsy diagnosed between 1980 and 2004 and a single focal lesion on neuroimaging were identified by review of the Rochester Epidemiologic Project database. Outcomes were divided into three categories: (1) seizure freedom for 1 or more years at last follow‐up, (2) ongoing seizures but not medically intractable epilepsy, and (3) medically intractable epilepsy or undergoing epilepsy surgery. We also evaluated the proportion who achieved seizure control without surgical intervention and whether lesion type predicted intractability. Key Findings: Of the 359 children with newly diagnosed epilepsy, 37 (10%) had a focal or hemispheric lesion on neuroimaging. Median age of diagnosis was 89 months (25th percentile 26 months, 75th percentile 142 months) and at follow‐up was 137 months (25th percentile 95 months, 75th percentile 211 months). Eighty‐three percent of children with malformations of cortical development, 67% with mesial temporal sclerosis, 33% with encephalomalacia, and 50% with vascular malformations had intractable epilepsy at follow‐up or underwent resective surgery for medically intractable epilepsy. Among the different etiologies, presence of encephalomalacia predicted the lowest likelihood of medical intractability or undergoing surgery (p < 0.01). At final follow‐up, 24 (65%) of our entire cohort was seizure free. Following surgery, seizure freedom was achieved in 80% with mesial temporal sclerosis, 67% with encephalomalacia, 67% with vascular malformation, and 50% with malformations of cortical development. There was no statistically significant difference between the different etiologies on neuroimaging and seizure freedom after surgery. Twelve children (32%) achieved seizure freedom with medical management alone. Significance: Focal lesions on neuroimaging confer a high risk of medical intractability among children with new‐onset epilepsy. However, 32% of this cohort achieved seizure remission with medical management alone, including 58% with encephalomalacia and 33% with mesial temporal sclerosis.     

A long‐term follow‐up study of Dravet syndrome up to adulthood

Purpose : We intended to elucidate the whole clinical course of Dravet syndrome (DS) comprehensively, from infancy through adulthood. Methods : Subjects were 31 patients with DS (14 with typical DS, and 17 with borderline DS) who were followed from childhood to at least 18 years of age. Their seizures, abilities, and electroencephalography (EEG) findings were investigated and statistically analyzed. Results : The clinical findings of the patients with typical DS and those with borderline DS became largely similar in adolescence and adulthood. Seizures were intractable in childhood in all patients, but suppressed in five (16.1%) during follow‐up. Thirty‐five (87.5%) of the 40 apparently generalized convulsive seizures that were captured by ictal EEG recording at 7 years of age or later were of focal origin. The seizure‐free outcomes were significantly correlated with the experience of <3 episodes of convulsive status epilepticus, and also with disappearance of spikes on the follow‐up EEGs. Mental outcomes involving less severe intellectual disability were correlated with the presence of occipital alpha rhythms in the background activity of the follow‐up EEGs. Mean age at the recording of the follow‐up EEGs was 23.8 years. Discussion : Prevention of the occurrence of convulsive status epilepticus was indicated to be critically important for the improvement of seizure prognosis in DS.     

Can ACTH therapy improve the long‐term outcome of drug‐resistant frontal lobe epilepsy?

Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long‐term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add‐on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6‐week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short‐term follow‐up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure‐free at the end of ACTH treatment maintained an excellent outcome, remaining seizure‐free at the end of follow‐up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double‐blind prospective studies are required to confirm our initial findings.     

Clinical presentation of epilepsy in six villages in an onchocerciasis endemic area in Mahenge,Tanzania

Aims. To describe the clinical manifestations of epilepsy and access to antiseizure treatment in Mahenge in Central Tanzania, an onchocerciasis endemic area with a high prevalence of epilepsy. Methods. A door‐to‐door epilepsy prevalence survey was conducted in four rural and two sub‐urban villages. Trained community workers used five screening questions to identify persons suspected to have epilepsy. Such individuals were interviewed and examined by a neurologist or a medical doctor with additional training in epilepsy, and were tested for Onchocerca volvulus antibodies. Results. A total of 221 out of 8,062 (2.74%) surveyed individuals were confirmed to have epilepsy. The median age at seizure onset was 12 years (interquartile range: 7–16). Seventy‐nine persons with epilepsy (PWE) (36.1%) had a family member with epilepsy, which was a sibling in 52.1%. Tonic‐clonic seizures (142 individuals; 64.2%) were the most common seizure type. Nodding seizures were reported in 12.7% of PWE; the majority of them living in rural villages. Persons with nodding seizures reported more frequent seizures, presented with more psychiatric symptoms, and more often had onchocerciasis antibodies than those with other seizure types. The high rate of individuals with a seizure onset at between seven and 16 years is characteristic of onchocerciasis‐associated epilepsy (OAE). Of the PWE, 77.9% met the criteria for the clinical case definition of OAE. Eighty‐three PWE (37.6%) were not taking any antiepileptic medication. Phenobarbital was the antiepileptic drug most commonly prescribed in 76.1% of treated PWE. Conclusion. The high prevalence of epilepsy in rural villages in Mahenge most likely is related to the high prevalence of OAE. To prevent children developing OAE, strengthening the onchocerciasis elimination programme in Mahenge is urgently needed. Moreover, a decentralised epilepsy treatment programme is also needed to provide uninterrupted access to affordable antiepileptic drugs for the many PWE living in rural villages in the Mahenge area.     

Effectiveness of multimodality treatment for autoimmune limbic epilepsy

We evaluated the outcome of multimodality treatment in autoimmune limbic epilepsy in 3 consecutive patients (2 male and 1 female; age 33–55 years) presenting with a combination of focal non‐convulsive status epilepticus, memory impairment, and psychosis. MRI showed right or bitemporal T2 or FLAIR hyperintensity. Video‐EEG showed seizures of right temporo‐occipital or bitemporal independent onset. Extensive workup failed to reveal infectious aetiology or an underlying tumour. However, the autoantibody panel was positive for one or more of these antibodies: anti‐VGKC, anti‐GABA_B, anti‐VGCC (P/Q, N types), and anti‐GAD65. All patients received: (1) conventional antiepileptic drugs including levetiracetam, lacosamide, phenobarbital, lamotrigine, and valproate; (2) immunomodulatory therapy including methylprednisolone, plasmapheresis, and intravenous immunoglobulin; and (3) rituximab. After a 4–6‐week in‐hospital course, the seizures resolved in all patients but 2 had persistent memory impairment. None had treatment‐related complications. At the time of last follow‐up, 2–3 months later, 2 patients remained seizure‐free while 2 had residual memory impairment. Our findings suggest that multimodality treatment with a combination of conventional AEDs, immunomodulatory therapy, and rituximab is effective and safe in autoimmune limbic epilepsy.     

Premature mortality risk in people with convulsive epilepsy: Long follow‐up of a cohort in rural China

Purpose: Detailed data on the mortality of epilepsy are still lacking from resource‐poor settings. We conducted a long‐term follow‐up survey in a cohort of people with convulsive epilepsy in rural areas of China. In this longitudinal prospective study we investigated the causes of death and premature mortality risk among people with epilepsy. Methods: We attempted to trace all 2,455 people who had previously participated in a pragmatic assessment of epilepsy management at the primary health level. Putative causes of death were recorded for those who died, according to the International Classification of Diseases. We estimated proportional mortality ratios (PMRs) for each cause, and standardized mortality ratios (SMRs) for each age‐group and cause. Survival analysis was used to detect risk factors associated with increased mortality. Key Findings: During 6.1 years of follow‐up there were 206 reported deaths among the 1,986 people with epilepsy who were located. The highest PMRs were for cerebrovascular disease (15%), drowning (14%), self‐inflicted injury (13%), and status epilepticus (6%), with probable sudden unexpected death in epilepsy (SUDEP) in 1%. The risk of premature death was 2.9 times greater in people with epilepsy than in the general population. A much higher risk (SMRs 28–37) was found in young people. Duration of epilepsy and living in a waterside area were independent predictors for drowning. Significance: Drowning and status epilepticus were important, possibly preventable, causes of death. Predictors of increasing mortality suggest interventions with efficient treatment and education to prevent premature mortality among people with epilepsy in resource‐poor settings.     

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI‐negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high‐resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow‐up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure‐free (Engel class IA). Twenty‐one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12‐month follow‐up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR‐negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI‐negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long‐term also remain stable. Modern imaging techniques could further improve the postsurgical seizure‐free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.     

Seizure outcomes following multilobar epilepsy surgery

Purpose: Outcomes following unilobar surgeries for refractory epilepsy have been well described. However, little is known about long‐term seizure outcomes following multilobar resections. The aim of the current study was to identify long‐term seizure control and predictors of seizure recurrence in this patient population. Methods: Records of patients who underwent multilobar epilepsy surgery at the Cleveland Clinic between 1994 and 2010 were retrospectively reviewed. A postoperative follow‐up of at least 6 months was required. Patients were classified as seizure free if they achieved an Engel class I at last follow‐up. Long‐term chances of seizure freedom were illustrated using a survival analysis, and predictors of recurrence were identified using Cox proportional hazard modeling. Key Findings: Sixty‐three patients with medically intractable epilepsy underwent multilobar surgical resections during the study period (mean follow‐up of 4.6 years). Predominant resection types included extended occipital (temporoparietooccipital, parietooccipital, temporooccipital: 57%), frontotemporal (21%), and temporoparietal (17%). Mean age at surgery was 21.4 years and mean age at seizure onset was 10.1 years. Fifty‐six percent of the patients underwent extraoperative invasive electroencephalography (EEG) evaluations. At 6 postoperative months, 71% (95% confidence interval (CI) 65–77) were seizure‐free (SF), 64% (CI 58–70) were SF at 1 year, 52% (CI 46–59) were SF at 5 years, and 41% (CI 32–50) remained SF at 10 years. Forty‐one patients had at least one breakthrough seizure after surgery (median timing of recurrence 6.1 months), with an Engel class 1 achieved again by last follow‐up in 12 of these 41 cases. Nine patients required a reoperation. Patients who underwent extended occipital/posterior quadrant resections had more favorable outcomes as compared to the other groups. With multivariate analysis, the type of resection (p = 0.03), preoperative auras (p = 0.03), an incomplete resection (0.03), and the presence of postoperative spikes (p = 0.0003) correlated with seizure recurrence. The risk of seizure recurrence for an incomplete resection was 2.3 (CI 1.53–3.36), preoperative aura 2.3 (CI 1.34–3.87), and postoperative spikes on surface EEG 2.5 (CI 1.29–4.71). Significance: A favorable outcome can be achieved in 41% of patients undergoing multilobar resections for epilepsy surgery at 10 years of follow‐up. Close to one‐third of patients who have breakthrough seizures after surgery are able to regain seizure freedom by last follow‐up. Predictors of recurrence include resection type (frontotemporal and parietotemporal resections did worse), presence of preoperative aura, an incomplete surgical resection, and the presence of postoperative interictal discharges on EEG.     

Effect of dosage failed of first antiepileptic drug on subsequent outcome

Purpose: 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. Methods: 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. Key Findings: 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). Significance: 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.     

Validation of a brief screening instrument for the ascertainment of epilepsy

Purpose: To validate a brief screening instrument for identifying people with epilepsy in epidemiologic or genetic studies. Methods: We designed a nine‐question screening instrument for epilepsy and administered it by telephone to individuals with medical record–documented epilepsy (lifetime history of ≥2 unprovoked seizures, n = 168) or isolated unprovoked seizure (n = 54), and individuals who were seizure‐free on medical record review (n = 120), from a population‐based study using Rochester Epidemiology Project resources. Interviewers were blinded to record‐review findings. Results: Sensitivity (the proportion of individuals who screened positive among affected individuals) was 96% for epilepsy and 87% for isolated unprovoked seizure. The false positive rate (FPR, the proportion who screened positive among seizure‐free individuals) was 7%. The estimated positive predictive value (PPV) for epilepsy was 23%, assuming a lifetime prevalence of 2% in the population. Use of only a single question asking whether the subject had ever had epilepsy or a seizure disorder resulted in sensitivity 76%, FPR 0.8%, and estimated PPV 66%. Subjects with epilepsy were more likely to screen positive with this question if they were diagnosed after 1964 or continued to have seizures for at least 5 years after diagnosis. Discussion: Given its high sensitivity, our instrument may be useful for the first stage of screening for epilepsy; however, the PPV of 23% suggests that only about one in four screen‐positive individuals will be truly affected. Screening with a single question asking about epilepsy yields a higher PPV but lower sensitivity, and screen‐positive subjects may be biased toward more severe epilepsy.     

Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?

PURPOSE: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes. METHODS: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery. RESULTS: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure-free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001). CONCLUSIONS: The majority of patients with focal-onset epilepsy became seizure free on AED treatment. MTS-related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.     

Interictal EEG prediction of response to antiepileptic drug monotherapy

Forty-eight patients had sleep-deprived EEGs prior to antiepileptic drug monotherapy. The majority were seizure-free after one year, or had more than 50% reduction in seizure frequency. Among those with normal EEGs 50% were seizure-free, while 75% with diffuse slowing, 44% with focal abnormality, and 83% with generalized epileptiform discharges were fully controlled. Freedom from seizures was achieved in 13% taking phenobarbital, 50% taking phenytoin, 63% taking carbamazepine, and 100% taking valproate. The sleep-deprived interictal EEG should be an integral part of initial assessment and drug selection in patients with clinical histories of convulsive seizure.