A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs

Purpose: Epilepsy is associated with near‐fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low‐frequency (LF) and high‐frequency (HF) power spectrum, respectively. Method: We performed a systematic review from the first date available to July 2011 in Medline and other databases; key search terms were “epilepsy”; “anticonvulsants”; “heart rate variability”; “vagal”; and “autonomous nervous system.” Original studies that reported data and/or statistics of at least one HRV value were included, with data being extracted by two independent authors. We used a random‐effects model with Hedges’s g as the measurement of effect size to perform two main meta‐analyses comparing LF and HF HRV values in (1) epilepsy patients versus controls; (2) patients receiving versus not receiving treatment; and (3) well‐controlled versus refractory patients. Secondary analyses assessed other time‐ and frequency‐domain measurements (nonlinear methods were not analyzed due to lack of sufficient data sets). Quality assessment of each study was verified and also meta‐analytic techniques to identify and control bias. Meta‐regression for age and gender was performed. Key Findings: Initially, 366 references were identified. According to our eligibility criteria, 30 references (39 studies) were included in our analysis. Regarding HF, epilepsy patients presented lower values (g ?0.69) than controls, with the 95% confidence interval (CI) ranging from ?1.05 to ?0.33. No significant differences were observed for LF (g ?0.18; 95% CI ?0.71 to 0.35). Patients receiving treatment presented HF values to those not receiving treatment (g ?0.05; 95% CI ?0.37 to 0.27), with a trend for having higher LF values (g 0.1; 95% CI ?0.13 to 0.33), which was more pronounced in those receiving antiepileptic drugs (vs. vagus nerve stimulation). No differences were observed for well‐controlled versus refractory patients, possibly due to the low number of studies. Regression for age and gender did not influence the results. Finally, secondary time‐domain analyses also showed lower HRV and lower vagal activity in patients with epilepsy, as shown by the standard deviation of normal‐to‐normal interval (SDNN) and the root mean square of successive differences (RMSSD) indexes, respectively. Significance: We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.     

Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis

Purpose: Because of the lack of head‐to‐head adjunctive‐therapy trials of antiepileptic drugs (AEDs) in refractory partial epilepsy, meta‐analyses of placebo‐controlled randomized controlled trials (RCTs) represent a potentially important source of evidence to guide treatment decisions. However, such indirect comparisons raise various methodologic issues that may hamper their relevance. Methods: All RCTs in adult refractory partial epilepsy were analyzed to assess whether efficacy outcomes are influenced by: characteristics of patients and trials ; use of last observation carried forward (LOCF) analysis; evaluation period (entire period versus maintenance period); and year of publication. A meta‐analysis of these AEDs was then performed taking these factors into consideration. Key Findings: Sixty‐three RCTs evaluating 20 AEDs were included. The following variables influenced efficacy estimates: (1) responder rates correlated positively with duration of the entire treatment period (p = 0.038); (2) response to placebo was significantly greater in the maintenance period than in the entire treatment period (p = 0.005); (3) responder rates increased over the years both for AEDs (p < 0.001) and for placebo (p = 0.001); (4) LOCF analysis overestimated responder rates for AEDs (p < 0.001) and for placebo (p = 0.001) compared with completer‐based analysis, and the overestimation correlated positively with withdrawal rates (p < 0.001). A meta‐analysis of available data showed large differences in efficacy ranking in relation to dose selection and type of analysis, but these were mostly nonsignificant due to statistical power limitations. Significance: Several methodologic issues hamper the relevance of indirect comparisons of AEDs in the adjunctive‐therapy of refractory partial epilepsy. Some of these issues could be overcome by improved standardization in the reporting of efficacy outcomes.     

Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: Systematic review and meta-analysis

Although adjunctive treatment with modern antiepileptic drugs (AEDs) is standard care in refractory epilepsy, it is unclear how much of the effect can be attributed directly to the AEDs and how much to the beneficial changes seen with placebo. Therefore, we performed a systematic review and meta-analysis of the evidence to determine the placebo-corrected net efficacy of adjunctive treatment with modern AEDs on the market for refractory epilepsy. Of 317 potentially eligible articles reviewed in full text, 124 (39%) fulfilled eligibility criteria. After excluding 69 publications, 55 publications of 54 studies in 11,106 adults and children with refractory epilepsy form the basis of evidence. The overall weighted pooled-risk difference in favor of AEDs over placebo for seizure-freedom in the total sample of adults and children was 6% [95% confidence interval (CI) 4–8, z = 6.47, p < 0.001] and 21% (95% CI 19–24, z = 17.13, p < 0.001) for 50% seizure reduction. Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the placebo-corrected efficacy of adjunctive treatment with modern AEDs is disappointingly small and suggest that better strategies of finding drugs are needed for refractory epilepsy, which is a major public health problem.     

托吡酯添加治疗难治性部分性癫癇疗效及安全性Meta分析

研究背景癫癇是中枢神经系统神经元异常放电所致慢性神经系统疾病。在过去20年中,涌现出约10余种新型抗癫癇药物,为癫癇患者的治疗提供了新的选择,其中托吡酯主要用于难治性部分性发作之添加治疗,本研究拟对其疗效和安全性进行系统评价,以期进一步对临床用药提供参考和借鉴。方法分别以托吡酯、妥泰、部分性发作、难治性、癫癇痫,以及topiramate、Topamax、add-ontreatment、adjunctive treatment、add-on therapy、adjunctive therapy、refractory partial seizure、refractorypartial epilepsy等中英文词汇为检索词,计算机检索美国国立医学图书馆（1995-2014年）、Cochrane临床对照试验中心注册库（1995-2014年）、Cochrane系统评价数据库（1995-2014年）、中国知网中国知识基础设施工程（1995-2014年）、万方数据库（1999-2014年）等,收集所有关于托吡酯添加治疗难治性部分性癫癇的随机双盲对照临床试验,经方法学质量评价后行Meta分析。结果共纳入13项随机对照试验,包括1622例难治性部分性发作患者。分析显示：托吡酯每周部分性发作减少率≥50%（OR=3.710,95%CI：2.870~4.810;P=0.000）、≥75%（OR=7.220,95%CI：3.310~15.750;P=0.000）及完全不发作（OR=3.380,95%CI：1.720~6.640;P=0.000）的患者比例均高于对照组;停药率除200 mg/d组外（OR=2.170,95%CI：0.470~9.950;P=0.320）,其余各亚组均高于对照组（600 mg/d：OR=2.090,95%CI：1.020~4.270,P=0.040;800 mg/d：OR=8.000,95%CI：1.390~46.140,P=0.020）。常见不良反应包括嗜睡、厌食、共济失调、注意力下降、头晕、疲劳、恶心、思维异常、肢体麻木和体重减轻,托吡酯组不良反应发生率均高于对照组。结论托吡酯添加治疗难治性部分性癫癇疗效显著,剂量维持在200 mg/d停药率与对照组相近;轻至中度不良反应较对照组常见,主要为中枢神经系统不良反应,其次为消化系统。     

颅脑损伤后预防应用抗癫痫药物疗效Meta分析

目的 探讨颅脑损伤后应用抗癫痫药(AEDs)预防创伤后癫痫的疗效.方法 广泛检索PubMed、Ovid、Springer、维普、CNKI等数据库,对相关文献进行严格评价,最终纳入的21篇文献通过Meta分析,研究预防应用AEDs对创伤后早期、晚期癫痫是否有作用,研究颅脑损伤类型(外伤、颅脑手术)对预防用药效果的影响及预防用药后患者死亡率等情况.结果 在对预防用药是否有意义评价中,差异有统计学意义(OR=0.66,Z=4.310,P=0.000),故支持给药;在对早期癫痫预防用药效果评价中,差异有统计学意义(OR=0.48,Z=3.980,P=0.000),苯妥英钠组(OR=0.53)比卡马西平组(OR=0.40)对早期癫痫的预防效果更优;在对晚期癫痫预防用药效果评价中,差异没有统计学意义(OR=1.05,Z=0.310,P=0.760);在对不同类型颅脑损伤预防用药效果评价中,都具有应用意义(脑外伤OR=0.48,颅脑手术OR=0.69);在预防用药对死亡率影响比较分析中,对患者的死亡率都没有影响(OR=0.82,Z=0.920,P=0.360).结论 在已研究的药物范围内,颅脑损伤后预防性应用AEDs可使癫痫发病率明显降低;苯妥英钠对早期癫痫的预防效果较好;各类AEDs对晚期癫痫的预防效果差异无统计学意义;在外伤后癫痫和颅脑手术后癫痫患者中预防应用AEDs效果无明显差异;预防应用AEDs后对患者死亡率没有明显影响.

Abstract：

Objective To determine the efficacy ofantiepileptic drugs (AEDs) on prevention of epilepsy after craniocerebral injury. Methods Related articles searched from the databases such as PubMed, Ovid, Springer, VP and CNKI were collected and strictly evaluated; 21 articles were finally selected. Whether pretreatment with AEDs played its role in epilepsy appeared in the early/late stages was discussed with Meta-analysis; the influences of different craniocerebral injury types (resulting from trauma or surgery) on the efficacy of anti-epilepsy prophylaxis, and the mortality rate of the patients performed pretreatment were analyzed with Meta-analysis. Results Pretreatment withAEDs could significantly improve the results (OR=0.66, Z=4.31, P=0.000); pretreatment with AEDs obviously decreased the rate of epilepsy appeared in the early stage (OR=0.48, Z=3.980, P=0.000), but did not statistically decrease the rate of epilepsy appeared in the late stage (OR=1.05, Z=0.310, P=0.760);pretreatment with diphenylhydantoin (OR=0.53) was more effective on epilepsy appeared in the early stage than pretreatment with carbamazepine (OR=0.40). Pretreatment with AEDs was all-effective considering different craniocerebral injury types resulting from trauma (OR=0.48) and surgery (OR=0.69). No significant differences were noted on the mortality rate of patients performed pretreatment and without pretreatment (OR=0.82, Z=0.920, P=0.360). Conclusion The inception rate of epilepsy can be decreased remarkably after anti-epilepsy prophylaxis with AEDs in patients after craniocerebral injury,and diphenylhydantoin has a better effect for epilepsy appeared in the early stage. No reasonable differences between various kinds of AEDs on epilepsy appeared in the late stage are noted. Pretreatment with AEDs enjoys a good result in both post-traumatic brain injury and craniotomy. Pretreatment can not affect the mortality rate of the patients.     

Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis

Purpose: Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme‐inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme‐inducing AEDs. This is currently unclear. Methods: Therefore, we performed a meta‐analysis of the evidence to determine the placebo‐corrected efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs versus modern enzyme‐inducing AEDs that are on the market for refractory focal epilepsy. Key Findings: Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled‐risk ratio (RR) in favor of enzyme‐inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77–3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26–8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme‐inducing AEDs over placebo was 2.28 (95% CI 2.03–2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23–4.67, p < 0.001) for seizure freedom. In a meta‐regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme‐inducing AEDs (eight studies) versus nonenzyme‐inducing AEDs (29 studies) was 1.01 (95% CI 0.77–1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure‐free outcome for enzyme‐inducing AEDs (six studies) versus nonenzyme‐inducing AEDs (19 studies) was 1.38 (95% CI 0.60–3.16, p = 0.43). Significance: Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs is similar to that of enzyme‐inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme‐inducing AEDs may be useful alternatives to enzyme‐inducing AEDs for treatment of refractory focal epilepsy.     

Retention rates of new antiepileptic drugs in localization-related epilepsy: a single-center study

Objectives – We evaluated long‐term retention rates of newer antiepileptic drugs (AED) in adults with localization‐related epilepsy retrospectively. Methods – We estimated retention rates by Kaplan–Meier method in all 222 patients (age ≥ 16) with localization‐related epilepsy exposed to new AED at the Tampere University Hospital. Results – There were 141 patients exposed to lamotrigine, 78 to levetiracetam, 97 to topiramate, 68 to gabapentin, and 69 to tiagabine. Three‐year retention rate for lamotrigine was 73.5%, levetiracetam 65.4%, topiramate 64.2%, gabapentin 41.7%, and tiagabine 38.2%. The most common cause for withdrawal of these AED was lack of efficacy. Conclusions – Our study suggests that there are clinically significant differences among gabapentin, lamotrigine, levetiracetam, tiagabine, and topiramate as treatment for focal epilepsy in everyday practice. Gabapentin and tiagabine seem to be less useful than the other three AED. Furthermore, our study supports the value of retention rate studies in assessing outcome of the drugs in clinical practice.     

The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials

Purpose: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta‐analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose–response relationship. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo‐controlled, double‐blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose–response relationships of pregabalin AEs. Key findings: Thirty‐eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose–response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. Significance: Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose–response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta‐analyses of AED tolerability profiles RCTs performed in different conditions.     

ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: A systematic review and meta-analysis

ObjectiveThe C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case–control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.MethodsDatabases were obtained from the Cochrane Library, MEDLINE, EMBASE, major American and European conference abstracts, and www.google.my for genetic association studies up to February 2010. All the case–control association studies evaluating the role of ABCB1 C3435T in pharmacoresistance to AEDs were identified. The new definition of treatment outcome from International League Against Epilepsy (ILAE) was used for including studies for sub-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using models of both fixed- and random-effects for comparisons of the alleles and genotypes with co-dominant (C/C vs. T/T, C/T vs. T/T), dominant (C/C + C/T vs. T/T), and recessive (C/C vs. C/T + T/T) models in overall and in ethnicity subgroups. The 19 studies were selected for the next sub-analysis based on the new definition of drug-responsiveness and drug-resistance from ILAE. The same analysis was also performed for treatment outcome and ethnicity subgroups.ResultsA total of 22 association studies including 3231 (47.8%) drug-resistant patients and 3524 (52.2%) drug-responsive patients or healthy controls (genotyped for C3435T) were pooled in this meta-analysis. The allelic association of ABCB1 C3435T with risk of drug-resistance was not significant under fixed-effects model, 1.06 (95% CI 0.98–1.14, p = 0.12) and random-effects model, 1.10 (0.93–1.30, p = 0.28) in overall and in the subgroup analysis by ethnicity. Similar results were also obtained for all genetic models in the stratified analyses by new definition of drug-resistance by ILAE and ethnicity subgroups. There was no publication bias.ConclusionWe failed to show an association between the ABCB1 C3435T polymorphism and the risk of drug-resistance suggesting a revision in contribution of this polymorphism in the multi-drug transporters hypothesis of pharmacoresistance to AEDs in epilepsy.     

Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review

Aims. In recent years, many different DNA mutations underlying the development of refractory epilepsy have been discovered. However, genetic diagnostics are still not routinely performed during presurgical evaluation and reports on epilepsy surgery outcome for patients with genetic refractory epilepsy are limited. We aimed to create an overview of the literature on seizure outcome following epilepsy surgery in patients with different genetic causes of refractory epilepsy. Methods. We systematically searched PubMed and Embase prior to January 2017 and included studies describing treatment outcome following epilepsy surgery in patients with genetic causes of epilepsy. We excluded studies in which patients were described with epilepsy due to Tuberous Sclerosis Complex or Sturge‐Weber syndrome (since this extensive body of research has recently been described elsewhere) and articles in which surgery was aimed to be palliative. Results. We identified 24 eligible articles, comprising a total of 82 patients who had undergone surgery for (mainly childhood‐onset) refractory epilepsy due to 15 different underlying genetic causes. The success rate of surgery varied widely across these different genetic causes. Surgery was almost never effective in patients with epilepsy due to mutations in genes involved in channel function and synaptic transmission, whereas surgery was significantly more successful regarding seizure control in patients with epilepsy due to mutations in the mTOR pathway. Patients with a lesion on MRI tended to have higher seizure freedom rates than those who were MRI‐negative. Conclusion. Although the evidence is still scarce, this systematic review suggests that studying genetic variations in patients with refractory epilepsy could help guide the selection of surgical candidates.     

Gender and duration of untreated psychosis: a systematic review and meta-analysis

Aim: Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta‐analysis on the role of gender in influencing DUP in first‐episode psychosis. Method: Systematic literature search in PubMed/Medline and Ovid/PsychINFO. Twenty‐seven studies presenting data on 4721 patients diagnosed with psychosis at their first episode (2834 males and 1887 females) were included in the analysis. Results: Samples had a higher proportion of males: odds ratio = 2.5 (95% confidence interval: 1.8–3.3). Mean age at first contact was 25.4 for males and 27.5 for females. Patients from non‐Western countries were older at first contact than patients from Western countries. Average DUP in schizophrenia was 64 weeks and did not differ between genders but was shorter in Western compared with non‐Western countries. Conclusion: Earlier age at first contact and larger incidence in males support the existence of specific gender differences in first‐episode psychosis; however, these are not associated with DUP length.     

Handedness correlates with the dominant Parkinson side: a systematic review and meta-analysis

Parkinson's disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross-sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel-Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right-handed patients, 2413 (59.5%) had right-dominant and 1644 (40.5%) had left-dominant PD symptoms. For the left-handed patients this relation was reversed, with 142 (40.8%) right-dominant and 206 (59.2%) left-dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71-2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand-side. Possible causal factors are discussed.     

Clinical utility of intraoperative electrocorticography for epilepsy surgery: A systematic review and meta-analysis

Despite the widespread use of intraoperative electrocorticography (iECoG) during resective epilepsy surgery, there are conflicting data on its overall efficacy and inability to predict benefit per pathology. Given the heterogeneity of iECoG use in resective epilepsy surgery, it is important to assess the utility of interictal-based iECoG. This individual patient data (IPD) meta-analysis seeks to identify the benefit of iECoG during resective epilepsy surgery in achieving seizure freedom for various pathologies. Embase, Scopus, and PubMed were searched from inception to January 31, 2021 using the following terms: "ecog", "electrocorticography", and "epilepsy". Articles were included if they reported seizure freedom at ≥12-month follow-up in cohorts with and without iECoG for epilepsy surgery. Non-English articles, noncomparative iECoG cohorts, and studies with <10% iECoG use were excluded. This meta-analysis followed the PRISMA 2020 guidelines. The primary outcome was seizure freedom at last follow-up and time to seizure recurrence, if applicable. Forest plots with random effects modeling assessed the relationship between iECoG use and seizure freedom. Cox regression of IPD was performed to identify predictors of longer duration of seizure freedom. Kaplan–Meier curves with log-rank test were created to visualize differences in time to seizure recurrence. Of 7504 articles identified, 18 were included for study-level analysis. iECoG was not associated with higher seizure freedom at the study level (relative risk = 1.09, 95% confidence interval [CI] = 0.96–1.23, p = .19, I² = 64%), but on IPD (n = 7 studies, 231 patients) iECoG use was independently associated with more favorable seizure outcomes (hazard ratio = 0.47, 95% CI = .23–.95, p = .037). In Kaplan–Meier analysis of specific pathologies, iECoG use was significantly associated with longer seizure freedom only for focal cortical dysplasia (FCD; p < .001) etiology. Number needed to treat for iECoG was 8.8, and for iECoG in FCD it was 4.7. We show iECoG seizure freedom is not achieved uniformly across centers. iECoG is particularly beneficial for FCD etiology in improving seizure freedom.     

Safety and efficacy of balloon angioplasty in symptomatic intracranial stenosis: A systematic review and meta-analysis

Background and purposeEndovascular treatment is offered for symptomatic intracranial stenosis (ICS) when medical therapy fails. The purpose of this meta-analysis is to evaluate the risks and effectiveness of balloon angioplasty (BA) alone.Materials and methodsSystematic review and meta-analysis of all available articles on BA for symptomatic ICS was conducted. Data was analyzed separately for > 70% (Group 1) and > 50% (Group 2) stenosis. The results of the Group 1 were compared with those of SAMMPRIS study to the extent possible.ResultsA total of 25 studies comprising 674 patients were included. The cumulative incidence of periprocedural (within 30 days) stroke and death were 16.3% (Group 1), 7.6% (Group 2) and 11.5% (all studies). Incidence rates of ischemic stroke in the qualifying artery territory during follow-up (per 100 patient-years) were 2.0, 2.4 and 2.3, any stroke and death during follow-up were 4.4, 7.4 and 6.9, restenosis rates were 4.9, 11.5 and 8.9 respectively.While comparison of cumulative incidences of periprocedural ischemic stroke between Group 1 (13.0%) and the medical arm from SAMMPRIS study(4.4%) showed a significant difference (P = 0.008), there was no significant difference between the Group 1 and the stenting arm from SAMMPRIS study(10.7%) in the same variable.ConclusionBalloon angioplasty for stenosis of more than 70% is likely to have similar outcome comparable to the stenting arm in the SAMMPRIS study, however it presents lower rates of late ischemic events and restenosis. These data may help deciding on the endovascular method of choice in case of medical therapy failure.     

Inflammatory mediators in human epilepsy: A systematic review and meta-analysis

BackgroundAccumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy.MethodsWe performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis.Results66 articles reporting on 1934 patients were included. IL-1ra, IL-1β, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1β, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, −19 and −22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1β and IL-10.ConclusionInflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment.