ILAE Commission of European Affairs Subcommission on European Guidelines 1998-2001: The provision of epilepsy care across Europe

PURPOSE: To assess the needs and resources available in the provision of basic epilepsy care across Europe. METHODS: A mailed questionnaire was used, the European Epilepsy Services inventory (EESI). The EESI was distributed to all 36 European chapters of the International League Against Epilepsy (ILAE), and answers were obtained from 32, a response rate of 89%. For the purpose of studying trends across Europe, the chapters were divided into a Western, an Eastern, a Central, and a Southern group. RESULTS: The survey results showed that there was a wide range in the number of physicians and specialists involved in epilepsy care across Europe, with a trend toward higher numbers of neurologists, pediatricians, and pediatric neurologists in Eastern Europe. Many different specialties were involved in epilepsy care, and many chapters reported differences in the provision of care across their countries, with less possibility for patients to see a specialist in the least provided areas, where most epilepsy patients were cared for by general practitioners and internists. Problems with high costs of the newer antiepileptic drugs were most pronounced in Eastern Europe. Problems with lack of comprehensive care and of epilepsy specialists, with stigma and social problems, and with insufficient professional education and knowledge about epilepsy were reported all across Europe. CONCLUSIONS: Knowledge about differences in the pattern of provision of epilepsy care and about the main problems encountered by the European ILAE chapters is of importance in the continuing efforts to improve management of epilepsy all over Europe.     

Assessing the unmet treatment need in partial-onset epilepsy: looking beyond seizure control

Patients with resistant epilepsy are often coprescribed multiple medications and are more likely to experience drug-drug interactions and adverse events (AEs). A new generation of antiepileptic drugs (AEDs) has been developed with improved safety/tolerability profiles. To evaluate the unmet treatment needs in epilepsy, a comprehensive search of the English-language literature was conducted on Medline and other databases using the terms "partial epilepsy" and "focal seizure," focusing on newer AEDs. Sixty-nine articles were identified. Most patients experienced AEs, which were generally mild-moderate in severity. Drug-drug interactions existed for 6 of 11 AEDs for which data were available. There is evidence for depressive symptoms being associated with zonisamide, and mood-stabilizing effects were shown for lamotrigine and pregabalin. Levetiracetam and eslicarbazepine improved cognitive function. Vigabatrin may increase the risk of developing psychosis. Health-related quality of life (HRQoL) was inversely correlated with seizure frequency. Discontinuation rates were often high, although treatment retention improved with slower dose titration. Adjunctive therapy with newer AEDs has the potential to enhance HRQoL and treatment continuation in patients with partial epilepsy. There remains room for improvement in the management of epilepsy, and better treatments and longer-term trials are needed to meet the special requirements of refractory patients.     

Utilization of primary care physicians in borderline personality

Objective

Individuals with borderline personality disorder (BPD) consistently demonstrate high patterns of utilization in both mental health and non-psychiatric settings. However, utilization of primary care physicians by these individuals has not been examined. In this study, we examined physician use patterns and hypothesized that primary care outpatients with BPD features would evidence higher numbers of primary care physicians seen, primary care treatment settings experienced, and specialists seen.

Method

Using a cross-sectional consecutive sample of 389 internal medicine outpatients and a self-report survey methodology, we examined the number of primary care physicians seen, primary care treatment settings experienced, and specialists seen by participants during the past 5 years in relationship to two self-report measures for BPD, the BPD scale of the Personality Diagnostic Questionnaire-4 and the Self-Harm Inventory.

Results

There were statistically significant between-group differences in the number of primary care physicians and specialists seen (not the number of primary care treatment settings) over 5 years, and BPD status according to both measures of BPD, with BPD patients reporting higher rates.

Conclusions

Patients with borderline personality symptomatology appear to see a greater number of primary care physicians and specialists than patients without these Axis II symptoms. These findings may reflect the underlying psychological processes of the disorder as well as a general pattern of over-utilization of healthcare services by these types of patients.     

癫痫患者经颅磁刺激运动诱发电位的研究

目的 探讨癫痫患者经颅磁刺激（ＴＭＳ）的运动诱发电位（ＭＥＰ）对癫痫的诊断价值。方法 对３５例癫痫患者和３０例正常对照组的脑运动皮质和第７颈椎和７颈椎水平神经根进行单脉冲磁刺激,引出ＭＥＰ。结果 与对照组比较,两组患者的皮质阈强度均增大,治疗组增大更明显;未治 的皮质潜伏期和中枢神经传导时间缩短,治疗组则无明显改变;三组的周围潜伏期无明显差异。癫痫类型,疗程,联合用药与否以及脑部病灶侧别对ＭＥＰ无     

Profile of Antiepileptic Pharmacotherapy in a Tertiary Referral Center in South India: A Pharmacoepidemiologic and Pharmacoeconomic Study

Summary: Purpose: To study the current pharmacotherapy practices of epilepsy and its economics in a developing country by correlating the epidemiology and economics of antiepileptic drug (AED) treatment in general epilepsy care and comprehensive epilepsy care.
Methods: We compared the AED-use profiles, efficacy, and tolerability at entry and at last follow-up for 972 patients seen at a comprehensive epilepsy care program in South India from 1993 to 1995. The relative cost was expressed as the average percentage of the per capita gross national product (GNP/capita) each individual spent for AED treatment.
Results: At entry, 562 (57.8%) subjects were receiving poly-therapy; at last follow-up, 743 (76.4%) patients were receiving monotherapy, an increase of 34.3% in the use of monotherapy. One or more adverse drug reactions were reported by 28.6% of patients at entry and by 19.8% at last follow-up. The proportion of patients who were seizure free increased from 29.0 to 44.8%. Carbamazepine (CBZ) was the most frequently used AED, followed by diphenylhydantoin (DPH), valproate (VPA), and phenobarbitone (PB). The relative cost (% GNP/capita) for standard AEDs were as follows: PB, 4.4%; DPH, 7.1%; CBZ, 16.8%; and VPA, 29.5%. The average annual cost of AED treatment per patient in U.S. dollars was $64.32 at entry and $47.73 at last follow-up. Reduction in polytherapy resulted in the net annual saving of $16,128 ($16.59 per patient, or 5.4% GNP/capita).
Conclusions: The more frequent use of relatively expensive drugs like CBZ and VPA and the use of polytherapy—still quite prevalent in developing countries—has escalated the cost of AED therapy. Although in recent years AEDs have become more available in developing regions, primary and secondary care physicians have not been adequately educated about the current trends in the pharmacotherapy of epilepsy.     

Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures

PURPOSE: Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of efficacy (tolerance), development of dependence, and the potential for drug abuse limit the clinical use of benzodiazepines (BZDs) for long-term treatment of epilepsy or anxiety. BZD ligands that are in current use act as full allosteric modulators of gamma-aminobutyric acid (GABA)-gated chloride channels and, on long-term administration, trigger a functional uncoupling between the GABAA and BZD recognition sites. Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP). METHODS: In the present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former name AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures. RESULTS: ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs. In dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138. CONCLUSIONS: The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures.     

Effectiveness of collaborative care for depression in Italy. A randomized controlled trial

Trial design

This was a multicenter cluster-randomized controlled trial.

Participants

A total of 227 patients ≥ 18 years old with a new onset of depressive symptoms who screened positive on the first two items of the Patient Health Questionnaire-9 (PHQ-9) were recruited by primary care physicians (PCPs) of eight health districts of three Italian regions from September 2009 to June 2011.

Intervention

PCPs of the intervention group received a specific collaborative care program including 2 days of intensive training, implementation of a stepped care protocol, depression management toolkit and scheduled meetings with a dedicated consultant psychiatrist.

Objective

The objective was to determine whether a collaborative care program for depression management in primary care leads to higher remission rate than usual PCP care.

Outcomes

Outcome was clinical remission as expressed on PHQ-9 < 5 at 3 months.

Randomization

An independent researcher used computer-generated randomization to assign involved primary care groups to the two alternative arms.

Blinding

PCPs and research personnel were not blinded.

Results

The 223 PCPs enrolled recruited 227 patients (128 in collaborative care arm, 99 in the usual care arm). At 3 months (n= 210), the proportion of patients who achieved remission was higher, though the difference was not statistically significant, in the collaborative care group. The effect size was of 0.11. When considering only patients with minor/major depression, collaborative care appeared to be more effective than usual care (P= .015).

Conclusions

The present intervention for managing depression in primary care, designed to be applicable to the Italian context, appears to be effective and feasible.     

妊娠合并癫痫患者的临床特征及处理对策

目的探讨妊娠合并癫痫患者的临床特征及处理对策。方法收集2010-02—2015-12我院产科分娩的62例妊娠合并癫痫患者的临床资料进行回顾性分析。结果症状性癫痫21例,隐源性癫痫36例,特发性癫痫5例;孕前停药5例,坚持规律服药42例,其中单药治疗24例,多药治疗18例,未坚持服药15例;妊娠期癫痫发作增加17例(27.4%),发作减少19例(30.7%),发作无变化26例(41.9%);自然分娩33例(53.2%),剖宫产29例(46.8%);新生儿窒息3例,低体质量儿4例,新生儿畸形1例。结论癫痫患者孕前进行咨询及评估,规范化抗癫痫药物治疗,妊娠期增加产检次数,多学科合作管理,可以降低母儿并发症,改善妊娠结局。     

Long-term seizure outcome of surgery versus no surgery for drug-resistant partial epilepsy: A review of controlled studies

A majority of patients with formerly drug-resistant temporal lobe epilepsy become seizure-free after surgery. However, apart from one 12-month randomized trial, it is unclear how many become seizure-free because of surgery. To determine the net benefit of surgery, we performed a systematic review and meta-analysis of the published evidence of how many patients in similar studies become seizure-free without surgery. Of 155 potentially eligible articles reviewed in full text, 29 (19%) fulfilled eligibility criteria. After excluding 9 publications, 20 studies form the base of evidence. Overall, 719 of 1,621 (44%) of patients with mostly temporal lobe surgery were seizure-free compared to 139 of 1113 (12%) of nonoperated controls [pooled random effects relative risk (RR) 4.26, 95% confidence interval (CI) 3.03–5.98]. The pooled risk difference in favor of surgery was 42% (95% CI 32–51%). We found no comparative outcome data in patients with extratemporal lobe epilepsy only. The available evidence from mostly nonrandomized observational studies indicates that in appropriately selected patients with drug-resistant temporal lobe epilepsy, the combination of surgery with medical treatment is 4 times as likely as medical treatment alone to achieve freedom from seizures.     

Recurrence rate of seizure following discontinuation of anti-epileptic drugs in patients with normal long term electroencephalography

Background:

The usefulness of electroencephalography (EEG) in predicting seizure recurrence after antiepileptic drugs (AED) tapering is a controversial subject. There have been no studies which tested the additional yield of long-term over routine EEG recordings in predicting seizure recurrence after AED withdrawal.

Objective:

The primary objective of our study is to determine the recurrence rate of seizure following AED withdrawal in patients with focal epilepsy, unknown cause who had normal long-term electroencephalography (LTEEG) and secondary objective is to analyze the variables that would predict seizure recurrence.

Materials and Methods:

This was a prospective observational study. A total of 91 patients were included. 62 patients who had normal routine and LTEEG entered the final phase of the study were followed-up regularly for 1 year or until seizure recurrence whichever was earlier.

Results:

A total number of 91 patients were enrolled for the first phase of the study. Of these, 13 (14.29%) patients had an abnormal routine EEG. Of the remaining patients, another 16 (17.58%) had abnormal LTEEG. The remaining 62 patients with normal routine and long-term EEG entered the final phase of the study. Of these, 17 patients (27.41%) had seizure recurrence during the follow-up while 45 (72.58%) remained seizure free until the end of the 1 year follow-up. The significant variables associated with a higher risk of seizure relapse were a positive past history of seizure recurrence on prior drug withdrawal (relative risk: 2.19, confidence interval: 1.01-4.74, P < 0.05) and the duration of epilepsy until seizure control was achieved (P < 0.009).

Conclusions:

The recurrence rate of seizure in patients with a normal LTEEG is 27.41%. A positive past history of seizure recurrence and a longer time to achieve seizure freedom with AED increased the risk of seizure recurrence.     

Collaborative care for depression in European countries: A systematic review and meta-analysis

Objectives

This is a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness of collaborative care compared to Primary Care Physician's (PCP's) usual care in the treatment of depression, focusing on European countries.

Methods

A systematic review of English and non-English articles, from inception to March 2014, was performed using database PubMed, British Nursing Index and Archive, Ovid Medline (R), PsychINFO, Books@Ovid, PsycARTICLES Full Text, EMBASE Classic + Embase, DARE (Database of Abstract of Reviews of Effectiveness) and the Cochrane Library electronic database. Search term included depression, collaborative care, physician family and allied health professional. RCTs comparing collaborative care to usual care for depression in primary care were included. Titles and abstracts were independently examined by two reviewers, who extracted from the included trials information on participants' characteristics, type of intervention, features of collaborative care and type of outcome measure.

Results

The 17 papers included, regarding 15 RCTs, involved 3240 participants. Primary analyses showed that collaborative care models were associated with greater improvement in depression outcomes in the short term, within 3 months (standardized mean difference (SMD) − 0.19, 95% CI = − 0.33; − 0.05; p = 0.006), medium term, between 4 and 11 months (SMD − 0.24, 95% CI = − 0.39; − 0.09; p = 0.001) and medium–long term, from 12 months and over (SMD − 0.21, 95% CI = − 0.37; − 0.04; p = 0.01), compared to usual care.

Conclusions

The present review, specifically focusing on European countries, shows that collaborative care is more effective than treatment as usual in improving depression outcomes.     

抗癫痫药物对癫痫患者甲状腺激素水平影响的研究

目的 研究癫痫患者甲状腺激素水平和抗癫痫药物对其影响以及与疗效之间的关系。方法 测定已确诊的45例未服用过抗癫痫药物的癫痫患者血清甲状腺激素水平并与30例健康对照组进行比较。再经卡马西平、苯妥英钠、丙戊酸钠三种抗癫痫药物分组单药治疗3个月、6个月、年后观察甲状腺激素水平的变化及与疗效之间的关系。结果 未服用抗癫痫药物的新诊断癫痫患者游离甲状腺素（FT4）水平显著低于健康对照组,经苯妥英钠、卡马西平分别治疗3个月、6个月、1年后T4、FT4、FT3显著低于治疗前水平,TSH无显著性变化。经丙戊酸钠治疗后的不同时间段各甲状腺激素水平与治疗前比较无显著性差异（P＞0．05）。甲状腺激素水平的变化与化疗效之间似无相关性。结论 癫痫的反复发作虽未经抗癫痫药物治疗已存在FT4水平的降低。苯妥英钠、卡马西平可明显造成癫痫患者的亚临床甲状腺功能降低（T4、FT4、FT3下降）,丙戊酸钠对患者甲状腺激素水平无显著影响。甲状腺激素水平的变化与疗效之间无相关性。     

Management Strategies for Refractory Localization-Related Seizures

Summary: Localization-related epilepsy, the most common type of seizure disorder, often provides major management problems. Five new antiepileptic drugs (AEDs) with different mechanisms of action have been licensed in the United Kingdom in the 1990s for adjunctive use in the management of poorly controlled partial seizures. These were, in chronologic order, vigabatrin, lamotrigine, gabapentin, topiramate, and tiagabine. Their practical deployment is explored here. Mention also is made of clobazam and acetazolamide. Combination therapy with two or even three AEDs having complementary pharmacologic effects can provide an essential contribution to the management of partial seizures. This article discusses some of the pharmacologic strategies used in treating patients with refractory localization-related epilepsy.     

Weight issues for people with epilepsy—A review

Summary   Weight gain or loss is not an integral part of epilepsy although a sedentary lifestyle can contribute to weight gain. Pharmacological treatment for epilepsy may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. Antiepileptic drugs (AEDs) associated with weight loss are felbamate, topiramate, and zonisamide. AEDs associated with weight gain are gabapentin, pregabalin, valproic acid, and vigabatrin and possibly, carbamazepine. Weight neutral AEDs are lamotrigine, levetiracetam, and phenytoin. In clinical practice it is critical to weigh patients regularly and AED selection should be based on each patient's profile without sacrificing therapeutic efficacy.     

Association of non-adherence to antiepileptic drugs and seizures, quality of life, and productivity: survey of patients with epilepsy and physicians

Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical outcomes, although few studies have examined this relationship. This study assessed barriers and drivers to adherence, its impact on quality of life, and the importance of the patient–physician relationship to adherence. Two cross-sectional online surveys were conducted among 408 adult patients with epilepsy and 175 neurologists who treat epilepsy patients. Twenty-nine percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents. Patient-oriented epilepsy treatment programs and clear communication strategies to promote self-management and patients’ understanding of epilepsy are essential to maximizing treatment and quality of life outcomes while also minimizing economic costs.