Difference In Seizure Frequency Research Articles

Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis.

Background and PurposeThe role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE.MethodsA standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size.ResultsThe random-effects model analysis revealed a pooled effect size of −5.96 (95% CI= −8.98 to −2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p<0.0001), with an overall effect size of −9.36 (95% CI=−13.24 to −5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect.ConclusionsThis meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

Efficacy analysis of vagus nerve stimulation for the treatment of drug resistant epilepsy: A report of 110 cases

Objective To explore the efficacy of vagus nerve stimulation (VNS) for the treatment of drug resistant epilepsy. Methods The clinical data of 110 patients with drug resistant epilepsy who underwent VNS at Department of Neurosurgery, Provincial Hospital Affiliated to Anhui Medical University (the First Affiliated Hospital of University of Science and Technology of China) from February 2014 to March 2018 were analyzed retrospectively. The frequency and severity of seizures were followed up by outpatient review, and the efficacy was analyzed according to the McHugh seizure outcome classifications. Results The results of McHugh grade of 110 patients were as follows: grade ⅠA in 10 cases, grade ⅠB in 6, grade ⅡA in 25, grade ⅡB in 7, grade ⅢA in 30, grade ⅢB in 8, grade Ⅳ in 1 and grade Ⅴ in 20, and 3 patients were lost to follow-up. There was significant difference in seizure frequency between preoperative and postoperative conditions (P 0.05). In terms of seizure types, there were significant difference in the distribution of the McHugh classifications between patients with seizures of unclassified onset, focal onset and generalized onset (all P<0.05). The frequency of seizures decreased gradually with prolonged VNS stimulation time(P<0.05). Conclusions VNS could significantly reduce the frequency of seizure. VNS has a better effect on seizures with focal onset and generalized onset, while it has a poor effect on seizure types that cannot be classified. With the increase of stimulation time, the therapeutic effect of VNS is gradually improved. However, the age, sex or duration of disease is not related to the effect of VNS. Key words: Epilepsy; Vagus nerve stimulation; Treatment outcome; McHugh seizure outcome classifications

Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program

ObjectiveWe have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation. MethodsOne hundred and thirty-two adults and children with TRE receiving CBD were studied prospectively. Participants were separated into two groups — either taking (CBD + clobazam) or not taking concomitant clobazam (CBD − clobazam). In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED). Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at baseline, 12, 24, and 48 weeks. Groups were compared at each respective time point in the study using generalized estimating equations (GEE) analyses. ResultsAll groups demonstrated statistically significant reductions in seizure frequency and severity from baseline (all P < 0.05). When participants on CBD + clobazam were compared with CBD − clobazam, there were no significant differences in seizure frequency and severity reduction between the groups at 12 weeks (both P > 0.05). When comparing groups with iAEDs vs. group without iAEDs, independent of coadministration of clobazam, no differences in treatment response were observed (all P > 0.05). Longitudinal analyses up to 48 weeks after therapy initiation did not reveal any differences in treatment response between groups. ConclusionThese analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.

Do certain subpopulations of adults with drug-resistant epilepsy respond better to modified ketogenic diet treatments? Evaluation based on prior resective surgery, type of epilepsy, imaging abnormalities, and vagal nerve stimulation

ObjectiveAdults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. MethodsChanges in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. ResultsResponder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. ConclusionsModified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.

Transcranial Direct Current Stimulation for Patients With Pharmacoresistant Epileptic Spasms: A Pilot Study.

Background: Epileptic spasms (ES) is a severe seizure type and lack of adequate methods for controlling of clinical attacks. Previous studies have indicated that cathodal transcranial direct current stimulation (tDCS) reduces seizure frequency for patients with epilepsy. ES are proposed to have a focal cortical origin. We hypothesized that patients with ES exhibit hyperactive network hubs in the parietal lobe, and that cathodal tDCS targeting the bilateral parietal region can reduce seizure frequency in patients with pharmacoresistant ES.Materials and Methods: The present study consisted of three basic phases: (a) a pre-treatment monitoring period for 14 days; (b) a consecutive 14-day treatment period during which patients were treated with 1 or 2 mA cathode tDCS for 40 min once per day; (c) and a follow-up period for at least 28 days. During the first 20 min of treatment, the cathode was placed over the right parietal lobe (P4) with the reference electrode over the contralateral supra-orbital area. In the second 20 min, the cathode was placed over the left parietal lobe (P3), with the reference electrode over the contralateral supra-orbital area. All patients received active tDCS treatment, and some patients underwent more than one treatment block. Patients maintained a seizure diary throughout the study. Antiepileptic drug therapy remained unchanged throughout the study. K-related samples Friedman tests and two-related samples tests were used to analyze data from all patients.Results: Seven patients with pharmacoresistant ES were included, receiving a total of eighteen 14-day blocks of tDCS treatment. We observed a significant difference in seizure frequency at the second month (p = 0.028, unadjusted), as well as a trend toward decreased seizure frequency at the fourth month (p = 0.068, unadjusted) of the first follow-up, relative to baseline. Three of seven patients (42.9%) exhibited sustained seizure reduction, while one (14.3%) experienced a short-term reduction in seizure frequency following cathodal tDCS treatment. Treatment was well tolerated in all patients.Conclusions: Repeated tDCS with the cathode placed over the bilateral parietal region is safe and may be effective for reducing seizure frequency in a subgroup of patients with pharmacoresistant ES.

Seizures and Encephalitis in Myelin Oligodendrocyte Glycoprotein IgG Disease vs Aquaporin 4 IgG Disease

Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non-multiple sclerosis-related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)-related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease. To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG-positive and MOG-IgG-positive patients. Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England. The difference in seizure frequency between the AQP4-IgG-positive and MOG-IgG-positive patient groups was determined. Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG-positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG-positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG-positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG-positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement. Patients with MOG-IgG-associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG-associated disease.

Terminal seizure frequency and its relation to SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with epilepsy. Several risk factors have been implicated, including early age of onset, tonic-clonic seizures and antiepileptic drugs. However, whether patients who die from SUDEP have a greater frequency of seizures in the few months before death is unclear. We investigated the terminal seizure frequency and its relation to SUDEP among a large group of patients with tonic-clonic seizures in rural West China. We used the database from the Convulsive Epilepsy Control and Management Program in West China, which routinely provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with probable SUDEP were included according to pre-set criteria. A verbal autopsy was undertaken for each case. By matching each patient's age, sex, date of joining the program, time in follow-up, and baseline seizure frequency, we set up a 1:5 ratio control group. SPSS 21.0 statistics were applied to compare the differences in seizure frequency 3months prior to SUDEP between patients with probable SUDEP and controls. Furthermore, the dynamic changes of terminal seizure frequency 6-9months, 3-6months, and 3months prior to SUDEP was also analyzed. A total of 41 patients who died from probable SUDEP were identified out of 7844 patients during 10years of follow-up. The SUDEP group had a significantly higher tonic-clonic seizure frequency 3months before their deaths than the control group (p=0.023). At the same time, their seizure-free rate was lower than the control group (p=0.025). Patients with probable SUDEP who were followed up over 12months were further studied as a subgroup. They had more tonic-clonic seizures 3months prior to death compared to the control group (p=0.010). They also had an increase in seizure frequency in their terminal phase (3months prior) compared to an earlier stage (3-6months prior) (p=0.029). Furthermore, the terminal PB dose in the SUDEP group was higher than the control group (p=0.002). Patients who died from SUDEP had more frequent tonic-clonic seizures 3months before their deaths. Higher seizure frequency increases the exposure to peri-ictal pathophysiological events, which possibly relate to SUDEP. This phenomenon may be due to the drug resistance potential of these patients or the high dose of PB. Further research is required to ascertain the underlying mechanisms of SUDEP.

Transcranial magnetic stimulation for the treatment of epilepsy.

Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy. To assess the evidence for the use of TMS in individuals with drug-resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side-effects. We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi-RCTs in EMBASE are now included in CENTRAL). Eligible studies were RCTs that were double-blinded, single-blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug-resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full-text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230. We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use. Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials. Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta-analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges.

Costs and Clinical Outcomes of Epilepsy Surgery in Children With Drug-Resistant Epilepsy

PurposeApproximately 20% of children with epilepsy are drug-resistant, incurring considerable costs. Epilepsy surgery has been shown to be an effective intervention in this population. This study provides an initial look at the costs associated with surgical management of children with drug-resistant epilepsy as compared with medical management alone. ProceduresIn a retrospective cohort study of children with drug-resistant epilepsy referred for possible surgical intervention, we compared direct costs of those treated surgically versus those offered surgery but managed medically instead. We also assessed the difference in seizure frequency between the two groups. FindingsThere were 94 total patients, 78 (83%) in the surgical group and 16 (17%) in the medical group. The median (25th-75th percentile) cost of the epilepsy surgery hospitalization was $118,400 ($101,900-$143,800). Total median annual follow-up costs, not including the cost of surgical hospitalization, were not significantly different between the two groups at 1- or 2-year follow-up. However, the surgical patients who were seizure-free at 1-year follow-up, and those that remained seizure-free at 2-year follow-up, had significantly lower costs compared with the medical group ($8000 versus $16,200, P = 0.04 and $4300 versus $7600, P = 0.05, respectively). The surgical group had significantly fewer seizures compared with the medical group at 1-year follow-up. ConclusionsAlthough epilepsy surgery is expensive and the overall costs of surgical and medical management are similar in the first 2 years, patients who achieved seizure freedom after surgery had lower costs compared with those treated medically.

The anti-depression effect of Xylaria nigripes in patients with epilepsy: A multicenter randomized double-blind study

PurposeThe comorbidity of depression in patients with epilepsy is common and treatment is still controversial. This pilot study was aimed at evaluating the efficacy and safety of Xylaria nigripes for treating depressive symptoms in patients with epilepsy during 12 weeks of treatment. MethodsA multicenter, double-blind, placebo-controlled, randomized superiority study was performed. A total of 104 patients with epilepsy who fulfilled the study criteria were randomized 1:1 to receive Xylaria nigripes (the Wu Ling group) or placebo (the placebo group) treatment in the 12-week period of study. The participants were visited on weeks 0, 2, 4, 8, and 12 of the treatment course. ResultsEighty-one patients finished all of the visits. The primary efficacy endpoint in this study was the total effective rate for depression, which was significantly greater in the Wu Ling group (51.3%, n=39) than in the placebo group (35.7%, n=42, 0.51–0.36=0.15, 95% CI −0.06 to 0.37, U=2.83, P=0.002) after 12 weeks of treatment. No differences in seizure frequency or changes in severity were found between the Wu Ling and the placebo groups. In addition, the quality of life and seizure worry subscale scores in patients with epilepsy were also improved more notably in the Wu Ling group than in the placebo group (P<0.05). Most of the adverse effects (AEs) in this study were mild and had no differences between the Wu Ling and the placebo groups. ConclusionXylaria nigripes could alleviate depressive symptoms within 12 weeks treatment and was well tolerated in patients with epilepsy.

Antiepileptic Drugs and Quality of Life in Patients with Epilepsy: A Tertiary Care Hospital-Based Study

ObjectivesThe present study evaluated patterns of the use of antiepileptic drugs (AEDs) and their impact on quality of life (QOL) in patients with epilepsy. MethodsIn this cross-sectional study, patients with epilepsy (age >18 years) receiving AEDs for at least 1 year were enrolled. Demographic, clinical, and treatment parameters were recorded. QOL was measured using the modified Quality of Life in Epilepsy Inventory-10 (QOLIE-10) questionnaire for epilepsy. ResultsOf 200 patients, 53.5% were males and 60% were younger than 30 years. Seizures were predominantly partial (58%) and of idiopathic origin (61%). Monotherapy to polytherapy ratio was 1:1, with 70% of the patients on one new AED. Clobazam (37%) was used most frequently followed by phenytoin (25.5%), levetiracetam (23%), oxcarbazepine (21.5%), and carbamazepine (21%). Patients on polytherapy experienced a significantly more number of adverse drug reactions than did those on monotherapy (P < 0.0001). The mean QOLIE-10 score was 74.58 ± 20.60. There was no significant difference in seizure frequency, number of adverse drug reactions, and QOLIE-10 score among patients receiving old and new AEDs. Multiple linear regression analysis identified increased seizure frequency (standardized β −0.157; P = 0.003), more number of AEDs (standardized β 0.107; P = 0.05) as well as adverse drug reactions (standardized β −0.692; P = 0.0001) as significant predictors of poor QOL. ConclusionsAppropriate tools for early detection, selection of rational and safer AED treatment options, and regular monitoring for adverse effects play a crucial role in achieving seizure freedom and optimal QOL in patients with epilepsy.

Evaluation of Kilifi epilepsy education programme: a randomized controlled trial.

ObjectivesThe epilepsy treatment gap is largest in resource-poor countries. We evaluated the efficacy of a 1-day health education program in a rural area of Kenya. The primary outcome was adherence to antiepileptic drugs (AEDs) as measured by drug levels in the blood, and the secondary outcomes were seizure frequency and Kilifi Epilepsy Beliefs and Attitudes Scores (KEBAS).MethodsSeven hundred thirty-eight people with epilepsy (PWE) and their designated supporter were randomized to either the intervention (education) or nonintervention group. Data were collected at baseline and 1 year after the education intervention was administered to the intervention group. There were 581 PWE assessed at both time points. At the end of the study, 105 PWE from the intervention group and 86 from the nonintervention group gave blood samples, which were assayed for the most commonly used AEDs (phenobarbital, phenytoin, and carbamazepine). The proportions of PWE with detectable AED levels were determined using a standard blood assay method. The laboratory technicians conducting the assays were blinded to the randomization. Secondary outcomes were evaluated using questionnaires administered by trained field staff. Modified Poisson regression was used to investigate the factors associated with improved adherence (transition from nonoptimal AED level in blood at baseline to optimal levels at follow-up), reduced seizures, and improved KEBAS, which was done as a post hoc analysis. This trial is registered in ISRCTN register under ISRCTN35680481.ResultsThere was no significant difference in adherence to AEDs based on detectable drug levels (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 0.74–2.90, p = 0.28) or by self-reports (OR 1.00, 95% CI 0.71–1.40, p = 1.00) between the intervention and nonintervention group. The intervention group had significantly fewer beliefs about traditional causes of epilepsy, cultural treatment, and negative stereotypes than the nonintervention group. There was no difference in seizure frequency. A comparison of the baseline and follow-up data showed a significant increase in adherence—intervention group (36–81% [p < 0.001]) and nonintervention group (38–74% [p < 0.001])—using detectable blood levels. The number of patients with less frequent seizures (≤3 seizures in the last 3 months) increased in the intervention group (62–80% [p = 0.002]) and in the nonintervention group (67–75% [p = 0.04]). Improved therapeutic adherence (observed in both groups combined) was positively associated with positive change in beliefs about risks of epilepsy (relative risk [RR] 2.00, 95% CI 1.03–3.95) and having nontraditional religious beliefs (RR 2.01, 95% CI 1.01–3.99). Reduced seizure frequency was associated with improved adherence (RR 1.72, 95% CI 1.19–2.47). Positive changes in KEBAS were associated with having tertiary education as compared to none (RR 1.09, 95% CI 1.05–1.14).SignificanceHealth education improves knowledge about epilepsy, but once only contact does not improve adherence. However, sustained education may improve adherence in future studies.

Sleep and mood disorders in epilepsy

Epilepsy has a prevalence of 1% in general population, sleep disorders are common complications. Determine the frequency of sleep disorders (SD) and excessive daytime sleepiness (EDS) in patients with epilepsy and to identify the factors that are related to those described. The factors analyzed included age, sex, type of epilepsy, duration of epilepsy disease, nocturnal seizures, frequency of seizures, electroencephalogram (EEG) interictal pathological, altered brain MRI, antiepileptic drug (AED) used; sleep quality, daytime sleepiness and mood disorders. 58 patients were evaluated by interview and questionnaires on sleep quality (Pittsburgh scale), the degree of EDS (Epworth scale) and anxiety-depression (hospital depression and anxiety (HAD). The rest of the data were obtained from medical history. SD among patients with epilepsy studied had a prevalence of 55%. Significant differences were found between patients with sleep disorders versus (vs) patients with normal sleep in the following variables: frequency of difficulty (1 attacks/month: 8 (25%) vs 1 (4%): p 0.03), EDS (Epworth scale) 8 (25%) vs 1 (4%): p 0.03), presence of anxiety (HAD scale) 11 (22%) vs 3 (6%): p 0.001; presence of depression (HAD scale) 1 (4%) vs 10 (20%): p 0003. No significant differences between epileptic patients with and without sleep disorders when analyzing the rest of the variables. Sleep disorders are common among patients with epilepsy and are associated with a higher frequency of daytime sleepiness, anxiety and depression. It was shown that epileptic patients with sleep disorders showed a significant difference in seizure frequency of 1 time/month. However, this difference was not observed with a lower seizure frequency, possibly due to insufficient sample size. This would also explain the lack of association of other variables such as temporal lobe epilepsy, interictal EEG, AED disease and sleep disorders. While it is known the deleterious effect of epilepsy on sleep architecture, it is important to consider mood disorders predisposing factors of such alterations. Laura Zuccolo.

The outlook for adults with epileptic seizure(s) associated with cerebral cavernous malformations or arteriovenous malformations

SummaryCerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs) are common: their asymptomatic prevalence on brain magnetic resonance imaging (MRI) is 1 in 625 and 1 in 2,000, respectively. The risk of epileptic seizure(s) for people with AVMs and CCMs affects their domestic, social, and professional lives, and may influence their decisions about treatment. This article summarizes the seizure risks for people with AVMs and CCMs, gleaned from published original articles indexed in OVID Medline and Embase before 1 January 2012. In the absence of prior intracranial hemorrhage and nonhemorrhagic focal neurologic deficit, a population‐based study in Scotland, United Kingdom, found that the 5‐year risks of first seizure were 8% for AVM and 4% for CCM; presentation with intracranial hemorrhage or focal neurologic deficit raised this risk for AVM (23%) but not for CCM (6%). Features associated with the occurrence of epileptic seizures for CCM are lesion multiplicity and cortical CCM location, whereas for AVM the most consistently reported associations are younger age, temporal location, cortical involvement, and nidus diameter &gt;3 cm. In the absence of prior intracranial hemorrhage and nonhemorrhagic focal neurologic deficit, the 5‐year risk of developing epilepsy following a first seizure is 58% for AVM and 94% for CCM, though there is no difference in the chance of achieving 2‐year seizure freedom in this time frame (45% AVM vs. 47% CCM). Observational case series describe encouraging differences in seizure frequency before and after AVM and CCM treatment, but the shortage of studies demonstrating dramatic effects in comparison to concurrent control groups justifies the need for more controlled studies, ideally with randomized treatment allocation when the benefits of AVM or CCM treatment are uncertain.

Video-EEG Monitoring Differences in Children with Frontal and Temporal Onset Seizures

ABSTRACTThe objective of this study was to explore the clinical manifestations and electroencephalogram (EEG) features in children with frontal and temporal onset seizures. The method used was video-EEG monitoring that was conducted for 24 h in children with seizure disorders. The results were as follows: There were fewer children with temporal EEG onset seizure (TOS) than with frontal EEG onset seizure (FOS) (p = 0.132). Within the TOS category, PTOS was most frequent, and ATOS was rare (p = 0.001). The mean duration of ATOS was longer than that of TOS and PTOS (p < 0.05). There were no significant differences in seizure frequency and nocturnal attacks between children with TOS and children with FOS. Furthermore, we observed the interictal EEG from three aspects: the background, the location of discharges, and the time of discharges. The frequency of the multi-focal and bilateral discharges of FOS was higher than that of TOS (p < 0.01). The FOS discharged easily and quickly spread to the bilateral hemisphere and formed secondary bilateral synchrony. Focal discharges predominated in TOS, and rarely showed the paroxysm of bilateral synchronous rhythm. Bursts of fast rhythms predominated in the onset of TOS. In contrast, there were a variety of ictal EEG in FOS. Finally, it was concluded that in the group of children studied, the clinical and EEG characteristics of TOS were different from those of FOS.

Generic Substitution of Antiepileptic Drugs: A Systematic Review of Prospective and Retrospective Studies

To systematically review the literature on generic antiepileptic drugs (AEDs), evaluate the efficacy and safety of generic AED substitution, and perform pharmacokinetic (PK) analysis using the American Academy of Neurology (AAN) scheme to classify evidence. PubMed and Cumulative Index to Nursing and Allied Health Literature searches from January 1, 1980, to October 15, 2010, were performed using the search terms anticonvulsant, antiepileptic drug, carbamazepine, divalproex, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pheno-barbital, phenytoin, primidone, topiramate, valproate, valproic acid, and zonisamide; bioavailability, bioequivalence, bioequivalency, bioequivalent, and substitution; and generic. Retrospective and prospective controlled studies of generic substitution of AEDs were included in the review. Non-English-language articles and uncontrolled clinical studies were excluded. Published articles were categorized using the AAN criteria for systematic reviews. We identified 156 articles. Of these, 20 met our inclusion criteria; 7 were retrospective studies, 6 were prospective studies in patients with epilepsy, and 7 were prospective studies in healthy subjects. All articles were rated Class I to Class III, using AAN criteria. The retrospective studies were categorized as Class III and showed a significant relationship between generic substitution and increased use of health care resources because of seizures or AED toxicity. Prospective studies were categorized as Class I, II, and III. Prospective studies in patients showed no differences between brand and generic drugs in PK parameters of bioequivalence. Three prospective studies in healthy subjects reported significant differences in maximum drug concentrations. Comparison of brand and generic drugs revealed no significant difference in seizure frequency; however, some prospective studies showed significant differences in PK parameters, primarily those not used for bioequivalence determinations. There is inconsistency between retrospective and prospective studies of generic AED substitution. The highest levels of evidence indicate that there should not be a problem with generic substitution, although some patients are more prone to problems with the generic products. Some evidence suggests that switches between multiple generic AED products in certain individuals may be problematic.

One-year seizure prognosis in epilepsy patients treated with antidepressants

To investigate the clinical effects of antidepressants on seizure frequency of patients with epilepsy treated with antiepileptic drugs, we retrospectively evaluated the 1-year course of seizure frequency. One hundred twenty-one patients with epilepsy treated with antidepressants and 300 patients with epilepsy not treated with antidepressants (controls) were the subjects of this study. Seizure frequency over the 1-year period of administration of antidepressants was retrospectively evaluated and compared with that for controls. In the patients with epilepsy taking antidepressants, seizure frequencies at four observation points (1, 3, 6, and 12months after starting antidepressants) were equivalent to those of the control group. There was no significant difference in seizure frequency between first- and second-generation antidepressants. Patients with epilepsy treated with antiepileptic drugs can take antidepressants without a significant risk of exacerbation of seizures. Most antidepressants can be used for psychiatric treatment of patients with epilepsy.

Effect of continuous positive airway pressure treatment on seizure control in patients with obstructive sleep apnea and epilepsy

In patients with epilepsy, improvement in seizure control with treatment of coexisting obstructive sleep apnea (OSA) has been reported, but there is lack of data on the effect of continuous positive airway pressure (CPAP) compliance on seizure control in these patients. We examined the variability in seizure frequency in patients who were CPAP compliant and those who were not CPAP compliant. We undertook a retrospective review of clinical and polysomnographic data of adult patients with OSA and epilepsy seen at the Boston University Medical Center Epilepsy and Sleep Clinics between 2000 and 2010. Data were reviewed for CPAP compliance and seizure frequency after at least 6 months of CPAP use. Only patients with no changes in antiepileptic drug regimens during CPAP trial were included. Of the 660 patients identified, 41 fulfilled inclusion criteria, of whom 28 were CPAP compliant and 13 were not CPAP compliant. In the compliant group, CPAP use led to decreased seizure frequency from 1.8 per month to 1 per month (p = 0.01). In the noncompliant group, no significant difference in seizure frequency was noted between baseline (2.1 per month) and at follow-up (1.8 per month, p = 0.36). Sixteen of 28 CPAP-compliant subjects were seizure free, whereas only 3 of 13 non-CPAP compliant subjects were seizure free [relative risk (RR) 1.54, p = 0.05]. Patients with epilepsy and OSA not compliant with CPAP treatment are at higher risk of seizures than are CPAP-compliant patients. To validate this observation, further prospective studies are warranted.

Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy

To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures. This randomized, double-blind, parallel-group study in adults with partial seizures included an 8-week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12-week, double-blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger-Hostility subscale score of the Profile of Mood States (POMS). Improvement with lamotrigine relative to levetiracetam was observed for mean +/- SD (standard deviation) change from baseline to the end of the maintenance phase (week 20) on the Anger-Hostility subscale (lamotrigine -2.0 +/- 8.2, levetiracetam -0.3 +/- 8.4; p = 0.024) (the primary endpoint); the Anger-Hostility subscale on weeks 5, 6, 7, 8, 9, 11, 12, 14, 16, 18, and 19; and the Total Mood Disturbance score on weeks 6, 7, 8, 9, 11, 12, 17, 19, and 20. Improvement (p < 0.05) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. No difference in seizure frequency was observed between groups. The most common adverse events with both medications were headache and dizziness. Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks. This difference was consistently observed throughout the treatment period. Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms.

Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures

The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wire implants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled in the study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1 mg/kg) and propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence available through EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test. There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in the EEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established as follow-up of this treatment.