Long-term seizure and psychosocial outcomes after resective surgery for intractable epilepsy

Resective surgery is considered an effective treatment for refractory localization-related epilepsy. Most studies have reported seizure and psychosocial outcomes of 2–5 years postsurgery and a few up to 10 years. Our study aimed to assess long-term (up to 15 years) postsurgical seizure and psychosocial outcomes at our epilepsy center. The Henry Ford Health System Corporate Data Store was accessed to identify patients who had undergone surgical resection for localization-related epilepsy from 1993 to 2011. Demographics including age at epilepsy onset and surgery, seizure frequency before surgery, and pathology were gathered from electronic medical records. Phone surveys were conducted from May 2012 to January 2013 to determine patients' current seizure frequency and psychosocial metrics including driving and employment status and use of antidepressants. Surgical outcomes were based on Engel's classification (classes I and II = favorable outcomes). McNemar's tests, chi-square tests, two sample t-tests, and Wilcoxon two sample tests were used to analyze the relationships of psychosocial and surgical outcomes with demographic and surgical characteristics. A total of 470 patients had resective epilepsy surgery, and of those, 50 (11%) had died since surgery. Of the remaining, 253 (60%) were contacted with mean follow-up of 10.6 ± 5.0 years (27% of patients had follow-up of 15 years or longer). Of the patients surveyed, 32% were seizure-free and 75% had a favorable outcome (classes I and II). Favorable outcomes had significant associations with temporal resection (78% temporal vs 58% extratemporal, p = 0.01) and when surgery was performed after scalp EEG only (85% vs 65%, p < 0.001). Most importantly, favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up [i.e., < 5 years (77%, 41%), 5–10 years (67%, 29%), 10–15 years (78%, 38%), and > 15 years (78%, 26%)]. Compared to before surgery, patients at the time of the survey were more likely to be driving (51% vs 35%, p < 0.001) and using antidepressants (30% vs 22%, p = 0.013) but less likely to be working full-time (23% vs 42%, p < 0.001). A large majority of patients (92%) considered epilepsy surgery worthwhile regardless of the resection site, and this was associated with favorable outcomes (favorable = 98% vs unfavorable = 74%, p < 0.001). The findings suggest that resective epilepsy surgery yields favorable long-term postoperative seizure and psychosocial outcomes.     

Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy

Vagus nerve stimulation (VNS) is a widely used adjunctive treatment option for intractable epilepsy. Most studies have demonstrated short-term seizure outcomes, usually for up to 5 years, and thus far, none have reported psychosocial outcomes in adults. We aimed to assess long-term seizure and psychosocial outcomes in patients with intractable epilepsy on VNS therapy for more than 15 years. We identified patients who had VNS implantation for treatment of intractable epilepsy from 1997 to 2013 at our Comprehensive Epilepsy Program and gathered demographics including age at epilepsy onset and VNS implantation, epilepsy type, number of antiepilepsy drugs (AEDs) and seizure frequency before VNS implantation and at the last clinic visit, and the most recent stimulation parameters from electronic medical records (EMR). Phone surveys were conducted by research assistants from May to November 2014 to determine patients' current seizure frequency and psychosocial metrics, including driving, employment status, and use of antidepressants. Seizure outcomes were based on modified Engel classification (I: seizure-free/rare simple partial seizures; II: > 90% seizure reduction (SR), III: 50–90% SR, IV: < 50% SR; classes I to III (> 50% SR) = favorable outcome). A total of 207 patients underwent VNS implantation, 15 of whom were deceased at the time of the phone survey, and 40 had incomplete data for medical abstraction. Of the remaining 152, 90 (59%) were contacted and completed the survey. Of these, 51% were male, with the mean age at epilepsy onset of 9.4 years (range: birth to 60 years). There were 35 (39%) patients with extratemporal epilepsy, 19 (21%) with temporal, 18 (20%) with symptomatic generalized, 5 (6%) with idiopathic generalized, and 13 (14%) with multiple types. Final VNS settings showed 16 (18%) patients with an output current > 2 mA and 14 (16%) with rapid cycling. Of the 80 patients with seizure frequency information, 16 (20%) had a modified Engel class I outcome, 14 (18%) had class II, 24 (30%) had class III, and 26 (33%) had class IV. Eighty percent said having VNS was worthwhile. Among the 90 patients, 43 patients were ≥ 18 years old without developmental delay in whom psychosocial outcomes were further analyzed. There was a decrease in the number of patients driving (31% vs 14%, p = 0.052) and working (44% vs 35%, p = 0.285) and an increase in the number of patients using antidepressant medication (14% vs 28%, p = 0.057) at the time of survey compared to before VNS. In this subset, patients with > 50% SR (60%) were taking significantly fewer AEDs at the time of survey compared to patients with unfavorable outcomes (median: 3 vs 4, p = 0.045). The associations of > 50% SR with the psychosocial outcomes of driving, employment, and antidepressant use were not significant, although 77% of this subset said VNS was worthwhile.This is the first study that assesses both seizure and psychosocial outcomes, and demonstrates favorable seizure outcomes of > 50% SR in 68% of patients and seizure freedom in 20% of patients. A large majority of patients (80%) considered VNS therapy worthwhile regardless of epilepsy type and psychosocial outcomes.     

Seizure outcome of intractable partial epilepsy in children

The intractable partial epilepsy outcome information is important in determining not only when epilepsy surgery evaluation should begin but also in deciding who would benefit and what is the likelihood of any benefit from surgery. Medical records of 50 children diagnosed with nontumor-related partial seizures, confirmed by video-electroencephalography (video-EEG), had at least one seizure per week and were followed for at least 2 consecutive years after video-EEGs were reviewed. There were 30 patients who continued with antiepileptic drug treatment after video-EEG. The seizure outcome analysis revealed a significant improvement of seizure control in the first year of follow-up but no difference between the first year and the following 3 years. Only 30% had excellent long-term outcome (seizure free or less than one seizure per 6 months). The presence of focal lesions on neuroimaging was the only risk factor of poor outcome. The other 20 patients underwent epilepsy surgery after video-EEG; 60% attained excellent outcome despite the fact that 90% had focal neuroimaging abnormality. Children whose partial epilepsy remained intractable after 1 year of antiepileptic drug treatment should be evaluated for candidacy of epilepsy surgery, particularly those who have focal lesions on neuroimaging.     

Seizure detection,seizure prediction,and closed-loop warning systems in epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.     

Vagal nerve stimulation in patients with refractory epilepsy. Effect on seizure frequency, severity and quality of life.

Vagal nerve stimulation using an NCP (Cyberonics) device has been suggested as a potential treatment for patients with epilepsy that has previously proven refractory. Ten patients in Northern Ireland have had this device implanted and been fully audited pre- and post-operatively. Twelve months post-implantation, five patients have demonstrated a greater than 50% reduction in seizure frequency. A statistical reduction in seizure severity of the ictal phase of the major seizures has also been shown. Improvement in the patients' overall quality of life has, however, not been demonstrated in parallel to seizure reduction.     

Psychiatric and psychosocial consequences of pediatric epilepsy

Psychiatric and psychosocial complications with pediatric epilepsy are more common than with other chronic medical illnesses. Epilepsy is a disorder of hyperexcitable neurons and may have direct neurophysiologic effects leading to psychiatric comorbidity. Epilepsy also requires significant lifestyle adjustment, and the psychosocial impact on children and their families may be severe. The scientific literature is underrepresented in terms of diagnosis and management of psychiatric and psychosocial comorbidity associated with pediatric epilepsy. However, recent scientific efforts have assisted in highlighting the impact of these comorbidities and in bringing them to greater clinical attention. This review incorporates the available evidence with an aim to describe effective strategies for diagnosis and management.     

Effects of psychosocial functioning,depression, seizure frequency,and employment on quality of life in patients with epilepsy

This study aimed to investigate the quality of life (QOL) in patients with epilepsy and its correlation with psychosocial impact, depression, seizure-related items, and living circumstances. One hundred two patients who visited the epilepsy clinic at Nagoya City University Hospital participated in this study. We used the Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P) as a measure of QOL, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) as the screening instrument for rapid detection of major depression, and the Side Effects and Life Satisfaction Inventory (SEALS) to evaluate psychosocial functioning, seizure-related items, and living circumstances. Significant correlations of the QOLIE-31-P overall score with these questionnaires and seizure-related or demographic variables were identified and analyzed by stepwise linear regression. The QOLIE-31-P overall score correlated significantly with the NDDI-E, SEALS overall score, number of anticonvulsants, frequency of focal seizure with impairment of consciousness or awareness (focal seizure), sheltered work, and employment. The stepwise linear regression showed that the QOLIE-31-P overall score was explained by the effects of psychosocial functioning, depression, frequency of focal seizure, and employment, in that order, with these factors explaining 74% of the variance. Thus, using both the SEALS and NDDI-E may be useful to detect some aspects of QOL in clinical settings.     

Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy.

OBJECTIVES: We wanted to investigate factors that are associated with frequency of interictal epileptiform discharges by investigating 303 patients with temporal lobe epilepsy (TLE). METHODS: We included all patients who consecutively underwent the adult presurgical evaluation program at our center and who had intractable, medial TLE with complex partial seizures due to unilateral medial temporal lobe lesions. The interictal EEG samples were automatically recorded and stored on computer. The location and frequency of interictal epileptiform discharges were assessed by visual analysis of interictal EEG samples of 2-minute duration every hour. RESULTS: There were 303 patients (aged 16-63) who met the inclusion criteria. The median interictal epileptiform discharge frequency was 15 IED/h, the median seizure frequency was 4 seizures/month. According to univariate analyses, we found that age at monitoring, epilepsy duration, and higher seizure frequency were associated with higher interictal epileptiform discharge frequency. In the logistic regression analysis, we found that higher seizure frequency (p < 0.001) and longer epilepsy duration (p = 0.007) were independently associated with higher spike frequency, while the age at monitoring was not. CONCLUSIONS: Seizure frequency and epilepsy duration (years of patient's life with seizure activity) were independently associated with IED frequency, suggesting that IED are modulated by seizures.     

Seizure frequency and the health-related quality of life of adults with epilepsy.

OBJECTIVE: To compare the health-related quality of life (HRQL) of a nonsurgical sample of adults with epilepsy with that of age- and gender-equivalent norms, and to analyze the relative importance of seizure frequency, time since last seizure, gender, and comorbidity on HRQL in the epilepsy sample. METHODS: Data were obtained from 139 adults with epilepsy from three US centers and published norms on the Medical Outcomes Study Short-Form 36 (SF-36). Patients were classified according to number of seizures over the prior 4 weeks (zero, one to five, six or more). Bivariate and multivariate modeling was used. RESULTS: HRQL scores for seizure-free patients were similar to the general population. Significant differences between seizure frequency groups were found for seven domains and the physical and mental component summary scales of the SF-36 (p<0.001). No differences were found in bodily pain. The largest differences were in physical role and social functioning, and general health (p<0.001). In the multivariate model, seizure frequency was a significant inverse predictor of HRQL across all domains (p<0.01 to 0.001). Men reported poorer physical function than women (p<0.05), and patients with a comorbid condition had poorer HRQL in the areas of pain (p<0.05) and general health perception (p<0.01). Time since last seizure was not related uniquely to HRQL. CONCLUSIONS: Seizure-free adults can have HRQL levels comparable with those of the general population. As seizure frequency increases, patients report more impaired HRQL, regardless of time since last seizure, gender, and comorbid status. Potential for difficulties in HRQL should be considered in clinical assessment and in evaluating treatment outcomes.     

Intentional seizure interruption may decrease the seizure frequency in drug-resistant temporal lobe epilepsy.

We investigated the nature of preictal subjective phenomena and whether they had any effect on the seizure frequency in 95 adult patients with medial temporal lobe epilepsy. Seventy-three (77%) patients indicated that they experienced seizure-provoking factors. Ten patients (11%) had prodromas independent of auras, while auras occurred in 89%. Forty-four patients (46%) reported that that they had tried to stop their seizures in the presence of prodroma or aura and this action had resulted in success at least once. Twenty-one patients (22%) regularly tried to stop their seizures because this effort was often successful according to their interpretation. Patients who reported that they could frequently inhibit their seizures had 1.8 +/- 1.6 seizures/month, a significantly lower mean seizure frequency than those 74 patients who did not do it regularly (4.6 +/- 4.8 seizures/month, P<0.001). Patients who reported regular experience in inhibiting intentionally their seizures more often had affective (P=0.05) and vertiginous auras (P<0.01) as well as isolated auras (P<0.05). Patients who experienced provoking factors showed the same seizure frequency as those who did not. Our results suggest that intentional seizure inhibition had an impact on the severity of drug-resistant epilepsy.     

Air travel and seizure frequency for individuals with epilepsy.

This study investigated whether air travel is associated with an increase in seizures for individuals with epilepsy. Thirty-seven participants monitored their seizure frequency for one week prior to flying and for one week after flying. For the sample as a whole, seizures were significantly more common after flying (p=.02). No seizures were reported as occurring during flight. Participants who experienced an increase in seizures after flying compared to those who did not (a) had a higher baseline of seizure frequency (p=.004), (b) were more likely to have previously experienced an increase in seizures after flying (p=.001), (c) were more worried about having a seizure while flying (p=.001) and (d) were more likely to avoid air travel (p=.02). Participants with complete seizure control prior to flying did not experience seizures after flying. Distance traveled, time zones crossed, duration of flight and direction of flight were not significantly different for those with seizure increase than for those without such an increase. This study suggests that air travel promotes an increase in seizures for those with a prior history of flight related seizures and a relatively high baseline seizure frequency.     

Pediatric intractable epilepsy: the role of presurgical evaluation and seizure outcome

Surgical experience with long-term follow-up is limited in childhood intractable epilepsy, compared with adult epilepsy. To assess the role of each presurgical evaluation modality and to identify prognostic factors for favorable seizure control after epilepsy surgery, 38 children with intractable epilepsy who underwent surgery were retrospectively reviewed. Among the available preoperative evaluation modalities, PET and neuropsychological testing showed the highest rates of positive results, whereas MRI was the most concordant with EEG findings. During a follow-up period of at least 12 months, 26 of the 38 patients showed favorable seizure control (Engel classifications I and II). The best seizure control was achieved in patients with a temporal resection and discrete lesion on magnetic resonance imaging. In spite of the invasive study, the less satisfactory results followed an extratemporal resection. We conclude that epilepsy surgery benefits children with intractable epilepsy and that the role of invasive study should be re-established according to the area of resection and presence of discrete lesion on MRI. Received: 23 June 1999 Revised: 7 August 1999     

Caregiver perceptions of seizure severity in pediatric epilepsy

Purpose:  Seizure severity has been investigated using multiple tools over the years, and its defining features continue to be debated. Severity ratings are necessary for medical, psychological, and epidemiologic investigations. Adults with epilepsy have been evaluated more than youth with epilepsy.
Methods:  Seizure severity was evaluated as part of a larger study that included youth and caregiver self-report measures of the emotional and social variables that occur in epilepsy.
Results:  The results indicate that a longer recovery time from the last seizure and a longer duration of seizure influence how severe a caregiver judges seizures. The usual elements such as type of epilepsy, frequency of seizures, and most recent seizure were not significantly related to severity rating. Behavior ratings were also not related to severity rating.
Discussion:  Clinicians often rely heavily on caregiver information during clinic visits to help inform treatment decisions; therefore, a standard measure of seizure severity from the caregivers' perception has clinical utility. Rather than assuming what makes a seizure severe to a parent, more research should be conducted on what elements contribute to severity, as judged by both the parent and youth.     

Predictors of seizure outcome after temporal lobectomy for intractable epilepsy

OBJECTIVES: To assess predictors of outcome of temporal lobectomy for intractable epilepsy. MATERIAL AND METHODS: In 63 adult patients operated with anterior temporal lobectomy during 198892, we used logistic regression analysis to assess predictors of being seizure-free (Engel's class I) 2 years after surgery. As potential predictors, we included the following variables: gender, age at operation, age at onset of seizures, epilepsy duration, etiology, generalized vs not generalized seizures, seizure frequency, intelligence quotient, ictal electroencephalography, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), side of resection, and extent of the resection. RESULTS: About 44% of the surgery patients were seizure-free (Engel's class I) 2 years after surgery. In multivariate analysis (n = 55), MRI pathology defined as atrophy in the temporal lobe, angioma, tumor or mesial temporal sclerosis (odds ratio, OR 7.4, 95%CI: 1.7-32.9) and extent of the hippocampal resection (increase of 1 cm) (OR 2.2, 95%CI: 1.1-4.6) predicted being seizure-free. CONCLUSION: Focal pathology in preoperative MRI and the extent of the hippocampal resection were the only significant predictors of being seizure-free after 2 years.     

Seizure suppression by adenosine-releasing cells is independent of seizure frequency

PURPOSE: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency. METHODS: Adenosine-releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs. RESULTS: Adenosine released from encapsulated cells exerted potent antiepileptic activity for >/=2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions. CONCLUSIONS: This study demonstrated that the frequency of test stimulations did not influence the seizure-suppressive potential of adenosine-releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure-discharge frequency.     

Interactions between seizure frequency, psychopathology, and severity of intellectual disability in a population with epilepsy and a learning disability

Despite observations associating lower IQ and psychopathology in epilepsy, the possible differential effects of varying severity of learning (intellectual) disability (LD) on the manifestation of psychopathology in people with LD and epilepsy have not been clarified. In this study of retrospectively collected data describing the epilepsy, learning disability, and psychopathology of 175 patients with epilepsy and LD over a 3-month period, we observed that 65 patients had no recent seizures, whereas 110 had experienced at least one seizure in the preceding 3 months. We found that depression and psychoses were more common in those with no seizures in the preceding 3 months, but that which of these psychiatric states was manifest was related to the severity of LD. Psychosis rates were higher in those with mild LD, whereas depression rates were higher in those with severe LD.     

Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utilization and impact on life in 1652 people with epilepsy.

OBJECTIVES: To describe the clinical characteristics of epilepsy in a representative sample of the UK population, including seizure frequency and severity; overall severity of epilepsy; patterns of anti-epileptic drug (AED) use; and the impact of epilepsy on patients' lives. Secondly, to determine if these characteristics differ according to age. METHOD: A large, geographically comprehensive survey of people with epilepsy by means of a postal questionnaire distributed by general practitioners to 3455 unselected patients receiving AEDs for epilepsy, regardless of age or type of epilepsy and including all regions of the UK. Data were collected on age and gender; age of onset of seizures; seizure frequency and severity; AED use and adverse effect levels; and impact on life of epilepsy. Sub-analyses were performed with stratification by epilepsy severity and age-group. RESULTS: There were 1652 completed replies. The mean age was 44.2 years; there were 47.2% males, 48.5% females (4.4% not recorded). The mean age at first seizure, 25.1 years, and the mean duration of epilepsy, 19.7 years, were comparable with previous studies. In the preceding one year, 51.7% of patients had no seizures; 7.9% one seizure, 17.2% 2-9 seizures and 23.2% 10 or more. Sixty-four percent of patients had epilepsy classified as mild and 32% severe. There was a marked and significant decrement of seizure frequency with increasing age. The most commonly used AEDs were carbamazepine (37.4%), valproate (35.7%), phenytoin (29.4%), phenobarbitone or primidone (14.2%) and lamotrigine (10.3%). Monotherapy was used in 68% of patients. Patients taking multiple AEDs reported significantly higher levels of adverse effects and worse seizure control. The major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life. The impacts listed varied with the epilepsy severity and age. CONCLUSIONS: Seizures remain uncontrolled in up to half of all people with epilepsy in the UK with significant impact on work, family and social life. Previously, there has been a deficiency of data on the characteristics of epilepsy in older people, although it is recognized that the condition is of increasing epidemiological importance in this age group. We have found clear differences in the clinical characteristics of epilepsy in older people, particularly that seizure frequency appears to decline with increasing age.     

生酮饮食疗法对难治性癫痫患者发作频率、血清单胺类神经递质水平的影响

目的探究生酮饮食结合抗癫痫药物对难治性癫痫患者发作频率、血清单胺类神经递质的影响。方法将2016年1月至2018年2月我院神经内科收治的72例难治性癫痫患儿纳入研究,所有患儿均在原有抗癫痫药物基础上进行至少3个月的生酮饮食治疗,于治疗后3、6、12个月时统计癫痫发作频率,复查脑电图评价脑部放电控制情况;于治疗6个月时采用韦氏儿童智力量表对患儿治疗前后的认知功能进行评价,测定事件相关电位P300及血清去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)水平。结果所有患儿均接受随访,治疗维持3、6、12个月的患者分别为72例、60例、38例。生酮饮食治疗3、6、12个月时临床发作控制有效率分别为40.3%、50%、55.3%,完全控制发作率分别为2.8%、18.3%、21.1%;脑电波减少有效率分别为50%、68.3%、76.3%;与治疗前比较,治疗6个月时患儿言语智商、操作智商、全量表智商得分未见显著性改变(P 0.05);与治疗前比较,治疗6个月时患儿N_2PL显著降低,P3波幅及血清NE、DA、5-HT等神经递质水平显著升高(P 0.05)。结论总体上生酮饮食结合抗癫痫药物治疗难治性癫痫有效,不仅可降低癫痫发作次数,也可一定程度改善患儿认知功能,其机制可能与其对神经递质的调控相关。     

Seizure frequency and severity: How really important are they for the quality of life of patients with refractory epilepsy

Introduction:

The data in the scientific literature about the significance of seizure severity and frequency for the quality of life (QOL) of patients with refractory epilepsy (RE) are contradictory.

Objective:

Our objective was to assess the impact of the seizure severity and frequency on the QOL of Bulgarian patients with RE.

Materials and Methods:

A total of 70 patients with RE were studied by examining the medical documentation and seizure diaries. All study participants completed quality of life epilepsy inventory (QOLIE-89). Seizure severity of only 59 patients who had a seizure in the last month was assessed by the Liverpool seizure severity scale.

Results:

A limited negative impact of the seizure severity and frequency on some aspects of the physical health, epilepsy, all aspects of the social health and epilepsy and the overall QOL has been demonstrated. A weak to moderate reverse correlation between the specified factors and the respective QOLIE-89 subscales has been found.

Conclusion:

The clinical factors seizure severity and seizure frequency have a limited negative impact mostly on the social aspects of QOL. The study results support the multidisciplinary approach to persons with epilepsy.