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.     

儿童癫痫及抗癫痫治疗对甲状腺功能影响的前瞻性研究

采用放射免疫分析法动态观察４０例儿童癫痫的甲状腺功能，结果发现癫痫本身对甲状腺功能无影响，而诱导肝酶类抗癫痫药如苯妥英钠、卡马西平、苯巴比妥可使Ｔ４降低。且随治疗时间的增长降低更明显，Ｔ３、ＴＳＨ无明显改变。丙戊酸钠对甲状腺功能无影响。提示对癫痫患儿要常规监测甲状腺功能，对同时有甲状腺疾病病史及其他可引起甲状腺功能改变的情况者，丙戊酸钠优于诱导肝酶类的抗癫痫药。     

拉莫三嗪治疗顽固性癫痫的临床观察

目的 观察添加拉莫三嗪（ＬＴＧ）治疗顽固性癫痫的疗效及安全性。方法 对３３例顽固性癫痫患者采用添加ＬＴＧ治疗开放性自身对照临床试验。结果 发作频度减少≥５０％１９例（５７．６％）,发作频率减少２６％～４９％,４例（１２．１％）,Ｌｅｎｎｏｘ０Ｇａｓｔａｕｔ综合征７例,疗效较佳。对部分性发作和泛化性发作的有效率分别为６５．４％和８０．６％,但统计学上无显著差异。ＬＴＧ与不同药物合用疗效无明显差异。仅     

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。     

传统抗癫痫药物和妥泰对成年癫痫患者生活质量的影响

目的 评价传统抗癫痫药物和妥泰对成年癫痫患者生活质量的影响。方法 102例临床新确诊的成年癫痫患者被随机分为两组：一组予以传统抗癫痫药物单药系统治疗(AEDs组)，另一组予以妥泰单药治疗(TPM组)。1个月后比较两组的发作频率和不良反应。并用QOLIE-30表对这102例癫痫患者进行生活质量评定。结果 TPM组的发作频率和不良反应均明显低于AEDs组，而生活质量总分明显高于AEDs组，尤其在前五项的评分中更加明显。结论 TPM能提高癫痫患者的生活质量，其改善生活质量的作用主要是通过控制发作和减轻不良反应实现的。     

Therapy for neurobehavioral disorders in epilepsy

Neurobehavioral disorders commonly affect patients with epilepsy. In addition to the behavioral changes during and immediately after seizures, the epileptogenic disorder of function often extends further into the postictal and interictal period. Cognitive impairments commonly affect attention, memory, mental speed, and language, as well as executive and social functions. Reducing seizure frequency and the antiepileptic drug burden can reduce these problems. Attentional deficits may respond to therapies for attention-deficit/hyperactivity disorder, but apart from patients with this comorbid disorder, their efficacy is unproven in other epilepsy patients. No effective therapies are established for other cognitive problems, but pragmatic, compensatory strategies can be helpful. Behavioral disorders include fatigue, depression, anxiety, and psychosis. Many of these disorders usually respond well to pharmacotherapy, which can be supplemented by psychotherapy. Cognitive and behavioral disorders can be the greatest cause of morbidity and impaired quality of life, often overshadowing seizures. Yet these problems often go unrecognized and, even when identified, are often undertreated or untreated.     

A new syndrome of mental retardation and epilepsy characterized by dense microsphere accumulation

Summary Dense microspheres (DMS) are enigmatic structures found within dendrites in the normal human cortex; their composition and function are unknown. We describe a case of a 29-year-old male with a history of mental retardation and epilepsy in whom the unique neuropathological finding was a marked excess of DMS, most notably in the neocortex. This is a previously undescribed neuropathological syndrome, and represents the first unequivocal association of DMS with a neurological disorder.     

Epilepsy and the impact of an epileptology clinic for patients with mental retardation and associated disabilities in an institutional setting

Summary:  Purpose: Epilepsy is a common problem in institutionalized patients with multiple handicaps. Limited data exist on the characteristics of epilepsy in this patient population and the impact of systematic evaluation by an epilepsy service.
Methods: We evaluated 138 patients with epilepsy, institutionalized at a facility that cares for 324 patients with multiple handicaps. Evaluation included EEG, MRI, and video-EEG monitoring. The medication regimen was changed according to seizure diagnosis and the status of seizure control. Follow-up was available for ≥6 months in 110 patients, 1 year for 89, and 1.5 years for 49 patients. We analyzed the seizure and epilepsy diagnosis in this population, as well as the seizure frequency after evaluation and treatment
Results: The 76 male and 62 female patients' ages ranged from 14 to 73 years. Seventy-three patients had fewer than one seizure per month, whereas 29 patients had at least one seizure per month. Of 131 patients taking antiepileptic drugs (AEDs), 62 were receiving monotherapy, and 69 were receiving two or more AEDs. At the last follow-up, overall 55% of patients had reduced seizure frequency, including 23% who became seizure free. Two of 36 patients had spontaneous seizure recurrence after being seizure free with no AEDs for 4 months in one patient and 3 years for the other. Attempts were made to discontinue phenobarbital, primidone, and clonazepam in 21 patients. However, these were discontinued in only five patients.
Conclusions: Epilepsy is heterogeneous in institutionalized patients with multiple handicaps. It is often responsive to medical therapy. Evaluation and treatment by epilepsy specialists had an overall favorable impact on seizure control.     

Response to sequential treatment schedules in childhood epilepsy: Risk for development of refractory epilepsy

PurposeTo investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood.MethodsAll children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. “Seizure control” was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and “refractory epilepsy” as failure of >2 drugs plus >1 seizure/month for ≥18 months.Results343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving “seizure control” was 70% and 86% at 5 and 10 years. 59% of patients were “controlled” with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally “controlled” with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years.ConclusionAfter failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy.     

Response to first antiepileptic drug trial predicts health outcome in epilepsy

Purpose: Failure to respond to the initial antiepileptic drug (AED) is a predictor of increased risk of pharmacoresistant epilepsy. Whether response to the first AED also predicts adverse health outcomes is unknown. Methods: This longitudinal study compared rates of major adverse health outcomes (loss of driving privileges, unemployment, divorce/separation, injury, emergency room admission, hospitalization, and death) in 33 patients who failed the first AED (cases) and 30 patients who became seizure‐free with the first AED (controls). Patient data were obtained by chart review and confirmed through a structured interview with each subject at 5–7 years after starting AED treatment. We also assessed between‐group differences in quality of life, depression, and adverse AED effects by using standardized instruments completed by each subject at the end of follow‐up. Key Findings: The number of major adverse health outcomes was similarly high during the first year of AED treatment [mean ± standard deviation (SD) 2.64 ± 0.99 for cases and 2.50 ± 1.14 for controls], but thereafter decreased to a greater extent in controls than in cases (p < 0.001). Controls had a higher cumulative probability of experiencing ≥1 year free from major adverse health outcomes compared to cases (p = 0.002). Two cases died during the follow‐up, both of sudden unexpected death. Cases had worse quality of life ratings than controls, whereas no significant between‐group differences were found for measures of depression and adverse AED effects. In a post hoc analysis limited to cases, patients who became seizure‐free with subsequent AED treatments showed for the first 4 years major adverse health outcome rates similar to those recorded in patients with persisting seizures. After 4 years, however, cases who achieved late seizure freedom tended to show a more favorable outcome. Significance: Patients with epilepsy failing the initial AED trial are at increased risk of experiencing adverse health outcomes, at least for the first 4 years after diagnosis. Incorporating these findings into clinical decision making may aid in reducing delays in surgical referrals for pharmacoresistant epilepsy.     

Levetiracetam for people with mental retardation and refractory epilepsy

Levetiracetam (LEV) is a novel antiepileptic drug (AED) with efficacy against a wide range of seizures types. The aim of this observational study was to assess its effectiveness in patients with mental retardation and refractory epilepsy. Sixty-four patients were started on adjunctive LEV after a 3-month baseline. LEV was initially dosed at 250 mg daily and increased by 250 mg every 2 weeks thereafter according to clinical response. Caregivers rated the patient's sleep, appetite, alertness, and behavior as poor (1), reasonable (2), or good (3) at each clinic visit. Patients were reviewed until one of four endpoints was reached: seizure freedom for at least 6 months, > or = 50% reduction in seizure frequency (responder) over a 6-month period, <50% reduction in seizure frequency (marginal effect) over a 6-month period, or LEV withdrawal due to lack of efficacy, adverse effects, or both. Twenty-four (38%) patients became seizure-free, 10 of whom were controlled on LEV 250 mg twice daily. An additional 18 (28%) patients were classified as responders, and 8 (12%) reported only marginal benefit from adjunctive LEV. Fourteen (22%) patients discontinued LEV (6 worsening seizures, 1 lack of efficacy, 7 adverse effects). Caregivers rated combined sleep, appetite, alertness, and behavior scores as "improved" at the end of follow-up (P<0.001). LEV improved seizure control in the majority of patients with mental retardation and may also have enhanced their quality of life.     

Stiripentol: efficacy and tolerability in children with epilepsy

PURPOSE: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed. METHODS: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial). RESULTS: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p<0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p<0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication. CONCLUSIONS: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.     

Behavioral comorbidity in children and adolescents with epilepsy

This cross sectional study assessed the prevalence of behavioral comorbidity and its association with epilepsy-related factors in children and adolescents with epilepsy. One hundred consecutive patients with active epilepsy, aged 6–16 years, were screened for behavioral comorbidity using the Child Behavior Checklist and those who qualified as having behavioral comorbidity were compared with those who did not have it. Behavioral comorbidity was found in 43 of 100 participants. Being treated with antiepileptic drug polytherapy (odds ratio 6.3, 95% confidence interval 1.4–17.3, p = 0.01) independently predicted behavioral comorbidity in the patients studied. The demonstrated high frequency of behavioral comorbidity in children with epilepsy suggests that pediatricians and pediatric neurologists should be sensitive to this fact in order to identify and manage behavioral comorbidity in children with epilepsy.     

Sexual dysfunctions and blood hormonal profile in men with focal epilepsy

PURPOSE: To evaluate the incidence of sexual dysfunction in men with focal epilepsy and to establish their hormonal profiles. METHODS: We prospectively analyzed sexual functions and hormone blood levels in 40 male patients (age ranged from 18 to 44 years, with an average age of 27.6+/-5.6 years) with refractory focal epilepsy. We used the Czech version of the structured questionnaire entitled International Inventory of Erectile Function (IIEF) to assess the patients' sexual functions. The subscales of this questionnaire separately evaluate erectile function (IIEF I), orgasmic function (IIEF II), sexual desire (IIEF III), intercourse satisfaction (IIEF IV), and overall satisfaction with sex life (IIEF V). In all of the patients, the following blood tests were performed: quantitative assessment of blood levels of prolactin (PRL), total testosterone (total-T), free androgen index (FAI), sexual hormone-binding globulin (SHBG), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), progesterone (PRG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). All these quantitative laboratory data were correlated with other clinical variables and with the results of the IIEF. chi2 and Wilcoxon tests were used for the statistical analysis. A p-value<0.05 was considered to be statistically significant. RESULTS: At least one of the types of sexual dysfunction, as defined by IIEF (IIEF I, II, and III), was found in 22 (55%) of the 40 patients (55%). Erectile dysfunction (IIEF I) was found in six (15%) of 40 patients, orgasmic dysfunction (IIEF II) in six (15%) of 40 patients, and loss of sexual desire (IIEF III) in 16 (40%) of 40 patients. According to other subscales of IIEF, 22 (55%) of 40 patients were not satisfied with sexual intercourse (IIEF IV), and 20 (50%) of 40 patients were not satisfied with their sex livee (IIEF V). None of the subscales of IIEF was significantly correlated with the age of the patients or with the duration of epilepsy. In patients with at least one of the sexual dysfunctions (IIEF I, II, and III), we found a statistically significant increase of FSH and SHBG, and a decrease of DHEAS and FAI in comparison with those in the patients with normal sexual functions. In patients with erectile dysfunction, we found the same changes and a significant increase of E2. In patients with orgasmic dysfunction, we found a statistically significant decrease of DHEAS. In patients with dysfunction of sexual desire, we noticed a significant increase of SHBG and a decrease of DHEAS and FAI. All patients with orgasmic dysfunction were being treated with carbamazepine (CBZ) in monotherapy or combination therapy. In patients with at least one type of sexual dysfunction (IIEF I, II, and III), we found a higher proportion of valproate treatment in monotherapy or combination therapy in comparison with CBZ. CONCLUSIONS: Our study showed a relatively high incidence of sexual dysfunction and dissatisfaction with sexual intercourse and sex life, as defined by the IIEF I-V questionnaire, in men with refractory focal epilepsy. The most frequent dysfunction in these patients is the impairment of sexual desire. However, our study indicates some specific hormonal changes related to various types of sexual dysfunction that are not related to antiepileptic drug treatment.