Vagus nerve stimulation in pediatric patients: Is it really worthwhile?

Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case–control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18 years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group — 1.33 ± 1.45 years; controls — 3.23 ± 3.11; p = 0.0001), abnormal findings in neurological examination (p = 0.01), history of previous ineffective epilepsy surgery (p = 0.03), and baseline seizure frequency (p = 0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy.     

El insomnio y la pobre calidad de sueño se asocian a un mal control de crisis en pacientes con epilepsia

ObjectivesThis study aimed to assess the presence of sleep disorders in patients with epilepsy and to analyse their association with seizure control.MethodsWe performed a cross-sectional study of patients with epilepsy, recruited consecutively between September 2017 and December 2018. Patients were classified as having good seizure control (no seizures in the last 4 weeks) or poor seizure control (at least one seizure in the last 4 weeks). We performed intergroup comparisons for demographic and clinical data, insomnia (Insomnia Severity Index [ISI]), excessive daytime sleepiness (Epworth Sleepiness Scale [ESS]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depression (Beck Depression Inventory-II [BDI-II]), and quality of life (Quality of Life in Epilepsy Inventory-10 [QOLIE-10]).ResultsThe sample included a total of 123 patients, of whom 31.7% had excessive daytime sleepiness (ESS ≥ 10), 50.4% had insomnia (ISI ≥ 10), and 53.6% had poor sleep quality (PSQI ≥ 5). According to our multivariate analysis, presence of seizures was associated with unemployment (odds ratio [OR] = 4.7; 95% confidence interval [CI], 1.36-19.2; P = .02), a higher number of antiepileptic drugs (OR = 5.87; 95% CI, 1.81-27.1; P < .001), insomnia (OR = 1.9; 95% CI, 1.1-9.3; P = .04), and poor sleep quality (OR = 2.8; 95% CI, 1.9-10.32; P = .01).ConclusionsSleep disorders are common in patients with epilepsy. Insomnia and poor sleep quality were associated with poor seizure control. These findings support the hypothesis that sleep disorders constitute a significant comorbidity of epilepsy, especially in patients with poor seizure control.     

Generalised convulsive status epilepticus in Singapore: Clinical outcomes and potential prognostic markers

PurposeTo study the characteristics, outcomes and prognostic markers of convulsive status epilepticus (SE) in Singapore.Methods62 adult admissions to the National University Hospital Singapore from 2002 to 2005 were studied. Ethnicity, history of epilepsy, educational subnormality, neuroimaging, seizure duration, length of stay, Modified Rankin Scale (MRS) pre and post discharge, blood glucose, creatine kinase, potassium, white cell and platelet count were recorded. An MRS ≥ 3 at discharge was defined as a poor outcome. ROCs of significant variables were plotted to identify the best test cut-offs.ResultsMean age was 59.2 years (range 20–94). 75.9% patients had epilepsy. Mean length of stay was 14 days (range 1–75). Univariate analyses revealed age (p = 0.01, OR 1.075, 95% CI 1.030–1.122), length of stay in ICU (p = 0.03, OR 1.299, 95% CI 1.014–1.665) and hospital (p = 0.014, OR 1.203, 95% CI 1.038–1.393) and hyperglycemia (p = 0.045, OR 1.327, 95% CI 1.007–1.750) associated with poor outcome. Test cut-off values for prognostic markers were established: age ≥ 55 years (ROC 0.790, sensitivity 72.3, specificity 85.7, PPV9 4.4%, NPV 48.8%) and serum glucose ≥ 7 mmol/L (ROC 0.737, sensitivity 72.3, specificity 80.0, PPV 93.5%, NPV 36.4%). A discriminant model using these variables was then constructed with probability scores for poor outcome.DiscussionAge, hyperglycemia and length of stay in hospital influenced outcome from convulsive SE in the local population with hyperglycemia being a novel prognostic marker. Some prognostic markers cited in the literature differed, highlighting the possibility that these indicators may vary across population groups.     

Predicting drug resistance in adult patients with generalized epilepsy: A case–control study

ObjectivesUsing an adult cohort of patients with generalized epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy (DRE), which if identifiable would allow patients to receive earlier treatment and more specifically individualized treatment plans.MethodsFor the case–control study, 118 patients with generalized epilepsy (GE) between the ages of 18 and 75 were included after selection from a database of 800 patients referred from throughout the Saskatchewan Epilepsy Program. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis.ResultsForty-four (37%) patients fulfilled the definition of DRE (cases), and seizures in 74 (63%) patients were not intractable (controls). Patients with DRE were significantly younger than the controls at the onset of epilepsy (6.6 vs. 18.8 years, p = < 0.001). Significant variables on univariate analysis were the following: epilepsy diagnosed prior to 12 years (OR: 12.1, CI: 4.8–29.9, p < 0.001), previous history of status epilepticus (OR: 15.1, CI: 3.2–70.9, p < 0.001), developmental delay (OR: 12.6, CI: 4.9–32, p < 0.001), and cryptogenic epilepsy (OR: 10.5, CI: 3.9–27.8, p < 0.001). Our study showed some protective factors for DRE such as a good response to first AED, idiopathic etiology, and history of febrile seizures. In the logistic regression analysis, two variables remained statistically significant: developmental delay and more than one seizure type.ConclusionOur study has identified a set of variables that predict DRE in patients with generalized epilepsy. Risk factors identified in our study are similar to those previously identified in pediatric studies, however, our study is specifically tailored to adult patients with generalized epilepsy.     

Vagus nerve stimulation: Outcome and predictors of seizure freedom in long-term follow-up

ObjectivesTo present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS).MethodsAll patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6–9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years.ResultTen patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P = 0.014, HR = 0.112 (95% CIs, 0.019–0.642), cortical dysgenesis P = 0.007, HR = 0.065 (95% CIs, 0.009–0.481) and younger age at implantation P = 0.026, HR = 7.533 (95% CIs 1.28–44.50) were independent predictors of seizure freedom in the long-term follow-up.ConclusionVNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS.     

GABRG2 rs211037 polymorphism and epilepsy: A systematic review and meta-analysis

PurposeThe gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.MethodsEight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.ResultsMeta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30–0.73, p = 0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42–0.83, p = 0.003) and dominant (OR 0.54, 95% CI 0.39–0.75, p = 0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.ConclusionThis study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.     

Determinants of depression among patients with epilepsy in Athens,Greece

ObjectiveDepression is common among patients with epilepsy. The aim of our study was twofold: to estimate the prevalence of a major depressive episode and to identify its determinants among patients with epilepsy treated in the largest Greek hospital in Athens.MethodsAll consecutive patients with epilepsy that visited the epilepsy outpatient clinic of Evangelismos General Hospital were invited to participate in the study. Ninety-four patients met our inclusion criteria.ResultsA diagnosis of a current major depressive episode was established in 21 out of 94 eligible to participate (22.3%) patients. Being a female was associated with a 19.68-fold increase in the odds of having a major depressive episode (95% CI 3.39–114.14, p = 0.001); being unemployed was associated with a 6.46-fold increase in the odds of having a major depressive episode (95% CI 1.23–34.07, p = 0.028), and each extra seizure experienced per month was associated with a 1.38-fold increase in the odds of having a major depressive episode (95% CI 1.03–1.85, p = 0.031).ConclusionUnemployment, female gender, and seizure control are important determinants of a major depression episode among patients with epilepsy.     

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS — A 24-month follow-up in Taiwan

ObjectivesMultiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population.MethodsWe conducted a one-group pretest–posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged < 18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children — IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist.ResultsVagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (< 12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children.ConclusionsVagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent–child relationships, especially in young children (< 12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age.     

Vagus nerve stimulation vs. corpus callosotomy in the treatment of Lennox–Gastaut syndrome: A meta-analysis

PurposeLennox–Gastaut syndrome (LGS) is an epileptogenic disorder that arises in childhood and is typically characterized by multiple seizure types, slow spike-and-wave complexes on EEG and cognitive impairment. If medical treatment fails, patients can proceed to one of two palliative surgeries, vagus nerve stimulation (VNS) or corpus callosotomy (CC). Their relative seizure control rates in LGS have not been well studied. The purpose of this paper is to compare seizure reduction rates between VNS and CC in LGS using meta-analyses of published data.MethodsA systematic search of Pubmed, Ovidsp, and Cochrane was performed to find articles that met the following criteria: (1) prospective or retrospective study, (2) at least one patient diagnosed with Lennox–Gastaut syndrome, and (3) well-defined measure of seizure frequency reduction. Seizure reduction rates were divided into seizure subtypes, as well as total seizures, and categorized as 100%, >75%, and >50%. Patient groups were compared using chi-square tests for categorical variables and t-test for continuous measures. Pooled proportions with 95% confidence interval (95% CI) of seizure outcomes were estimated for total seizures and seizure subtypes using random effects methods.Results17 VNS and 9 CC studies met the criteria for inclusion. CC had a significantly better outcome than VNS for >50% atonic seizure reduction (80.0% [67.0–90.0%] vs. 54.1% [32.1–75.4%], p < 0.05) and for >75% atonic seizure reduction (70.0% [48.05–87.0%] vs. 26.3% [5.8–54.7%], p < 0.05). All other seizure types, as well as total number of seizures, showed no statistically significant difference between VNS and CC.ConclusionsCC may be more beneficial for LGS patients whose predominant disabling seizure type is atonic. For all other seizure types, VNS offers comparable rates to CC.     

Seizure-related injuries in children and adolescents with epilepsy

BackgroundChildren with epilepsy are reported to be at a greater risk of injuries compared with their peers who do not have epilepsy.ObjectivesWe set out to determine the frequency and pattern of seizure-related injuries in children with epilepsy seen at the University College Hospital (UCH), Ibadan, Nigeria.MethodsConsecutive cases of epilepsy seen at the pediatric neurology clinic of the UCH, Ibadan over a period of 6 months were evaluated for injuries in the preceding 12 months using a structured questionnaire. These were compared with age- and sex-matched controls.ResultsA total of 125 children with epilepsy and 125 age- and sex-matched controls were studied. Injuries occurred more frequently in children with epilepsy than in their peers (p = 0.01, OR 1.935, 95% CI 1.142–3.280). Epilepsy was generalized in 80 (64.0%), and localization-related in 45 (36.0%). Idiopathic epilepsy accounted for 74 (59.2%), and the remaining 51 (40.8%) had remote symptomatic epilepsy. Fifty-seven (45.6%) children had suffered seizure-related injuries with multiple injuries in 31 (24.8%). The most frequent were skin/soft tissue lacerations (26.4%), injuries to the tongue and soft tissues of the mouth (19.2%), minor head injuries (15.2%), and dental injuries with tooth loss (8.0%). There was a statistically significant association between seizure frequency and seizure-related injuries (p = 0.002). Children on polytherapy had a significantly higher frequency of seizure-related injuries (p < 0.001).ConclusionEpilepsy is a major risk factor for injuries in childhood. High seizure frequency increases the risk of multiple injuries in children with epilepsy.     

The aetiology of convulsive status epilepticus: A study of 258 cases in Western China

PurposeTo investigate the characteristics of the aetiologies of convulsive status epilepticus (CSE) in Western China and to identify the relationships of these aetiologies with the prognoses.MethodsConsecutive registration and prospective observation of 258 cases of CSE in the Sichuan Epilepsy Center were performed from 1996 to 2010 to study the aetiology of CSE. The relationships of the aetiologies with the demographics, outcomes and complications of CSE were analysed using a logistic regression model.ResultsThe mean age was 37.6 ± 20.21 years. The majority of the CSE (62.4%) cases were acute symptomatic cases, and the primary cause was central nervous system (CNS) infection (33.7%). Histories of epilepsy were present in 51.9% of the patients. Pre-existing epilepsy occurred due to discontinuation or reduction of antiepileptic drugs (AEDs) in 31.3% of the CSE patients. Anoxia/poisoning (p < 0.05, OR 8.0, 95% CI 1.34–47.77) was an independent predictor of mortality. CNS infections (p < 0.001, OR 8.99, 95% CI 3.52–22.92), cerebrovascular diseases (p =0.001, OR 6.75, 95% CI 2.11–21.61) and anoxia/poisoning (p < 0.01, OR 7.64, 95% CI 1.93–30.21) were the major risk factors for complications associated with CSE.Conclusions(1) Compared to developed countries, CNS infections seemed to be more likely to be the cause of CSE in developing countries. (2) Noncompliance with AEDs among patients with epilepsy was a prominent and avoidable trigger of CSE.     

Risk factors for remote seizure development in patients with cerebral vein and dural sinus thrombosis

PurposeWe aimed to define the possible risk factors for acute and remote seizures in patients with cerebral vein and sinus thrombosis (CVST).MethodNinety-four patients were recruited prospectively at Al-Zahra Hospital, Isfahan, Iran, between April 2007 and April 2012. To identify seizure predictors, we compared demographic, clinical and imaging factors between patients with or without acute and remote seizures.ResultsOf the 94 patients, 32 (34%) experienced at least one seizure after CVST development. Bivariate analysis showed a significant association of remote seizure with loss of consciousness at presentation (P = 0.05, OR: 5.11, 95%CI: 1.07–24.30), supratentorial lesions (P = 0.02, OR: 9.04, 95%CI: 1.04–78.55), lesions in the occipital lobe (P = 0.00, OR: 12.75, 95%CI: 2.28–71.16), lesions in the temporal and parietal lobes, thrombophilia (P = 0.03, OR: 5.87, 95%CI: 1.21–28.39), seizure in the acute phase (P = 0.00, OR: 13.14, 95%CI: 2.54–201.2) and sigmoid sinus thrombosis (P = 0.00, OR: 12.5, 95%CI: 2.23–69.79). Seizures in the acute phase were also more common in patients with paresis (P = 0.00, OR: 4.88, 95%CI: 1.91–12.46), hemorrhagic lesions indicated by imaging (P = 0.02, OR: 2.77, 95%CI: 1.08–7.10), supratentorial lesions, lesions in the frontal (P = 0.01, OR: 3.81, 95%CI: 1.28–11.31) and parietal lobes (P = 0.00, OR: 5.16, 95%CI: 2–13.29), thrombophilia and history of miscarriage (P = 0.03, OR: 2.91, 95%CI: 1.07–7.91). No factor predicted acute or remote seizure in a multiple logistic regression analysis.ConclusionOur results demonstrate that seizure development in the acute phase is the most significant factor for development of remote seizure. Parenchymal lesions in the supratentorial area were also found to be associated with both acute and remote seizures. However, no factor was predictive of acute or remote seizures in a multivariate analysis.     

Self-esteem in adolescents with epilepsy: Psychosocial and seizure-related correlates

PurposeThis study evaluated self-esteem in adolescents with epilepsy and its association with psychosocial and disease-related variables.MethodsThis was a cross-sectional study with patients enrolled between January and June 2010. Culture-Free Self-Esteem Inventory for Children (CFSEI-2) was administered to 140 children with epilepsy and 50 children with asthma, aged 10–18 years attending mainstream schools.ResultsAdolescents with epilepsy had a significantly lower overall self-esteem score when compared with those with asthma, 17 ± 5.21 versus 19.4 ± 3.83, respectively (P = 0.005). Thirty-one (22.1%) children with epilepsy compared with 4 (8.3%) with asthma had overall self-esteem score below the cutoff (P = 0.034). There was a significant correlation between overall self-esteem score and duration of epilepsy, Hospital Anxiety and Depression Scale (HADS) anxiety score, HADS depression score, and Strengths and Weaknesses of ADHD symptoms and Normal-Behaviors (SWAN) rating combined score. The impact of various correlates on individual domains was not identical. Independent factors associated with low overall self-esteem were HADS depression score (OR: 1.62; 95% CI: 1.2, 2.2; P = 0.002), duration of epilepsy (OR: 1.4; 95% CI: 1.04, 1.88; P = 0.024), and father employment status economically inactive (OR: 11.9; 95% CI: 1.07, 125; P = 0.044). Seizure-free ≥ 12 months was a favorable factor that was less likely to be associated with low self-esteem (OR: 0.14; 95% CI: 0.02, 0.81; P = 0.028).ConclusionSelf-esteem was compromised in adolescents with epilepsy. A significant correlation between self-esteem and psychological comorbidities was demonstrated. Enhancing social support and education programs may improve the self-esteem and, ultimately, the lives of adolescents living with epilepsy.     

Perceived need for restrictions on activity for children with epilepsy

BackgroundChildren and youth with epilepsy have long been subjected to excessive restrictions on extracurricular activities due to concerns over risk of injury. Over time physicians and medical regulatory associations have liberalized the advice given for people with epilepsy to promote independence, self-esteem and general health benefits of physical activity. Current evidence suggests that few restrictions are needed for children with epilepsy beyond water-related precautions and avoidance of very high-risk activities. However, more stringent restrictions on daily activities may be imposed by caregivers. This study was aimed at exploring current perceptions of parents regarding restrictions on activity for children with epilepsy and the child’s perspective on restrictions related to the diagnosis.MethodsA self-administered questionnaire was offered to a sample of parent-child dyads of children/youth with epilepsy attending summer camp for children with epilepsy age 8–18 years. A 10-item validated HARCES Parent Scale of Childhood Epilepsy was completed by the parent/guardian and a modified-HARCES completed by the child. The primary objective was to assess the degree of restrictions placed on children with epilepsy from the perspective of child and parent assessed independently. Agreement of perceived restrictions between parent-child dyads was also determined.Results21 parent/guardian-child pairs were recruited with mean age of children/youth 12.7 years (range 9–16 years). Total HARCES scores for parents and guardians ranged from 11–26 (x = 16.5; SD 4.9) while total scores for children with epilepsy similarly ranged from 10–25 (x = 15.2; SD 4.9). There were no differences in total parent scores when analyzed by child's age (< 13 or > 13 years), gender, age of seizure onset, seizure frequency or seizure type. Total HARCES scores showed no agreement between parent and child pairs with correlation of 0.2798 (95% CI − 0.173–0.635).ConclusionsChildren and youth with epilepsy often face activity restrictions based on fear of perceived risk of injury. This small sample shows evidence that even more permissive parents and his/her children still feel limited by such restrictions. Parents and children do not perceive these restrictions in the same way despite similar education by physicians highlighting an important secondary role of epilepsy camps in targeting misperceptions and educating families on appropriate precautions.     

Clinical features of the pre-ictal state: Mood changes and premonitory symptoms

Identifying the pre-ictal state clinically would improve our understanding of seizure onset and suggest opportunities for new treatments. In our previous paper-diary study, increased stress and less sleep predicted seizures. Utilizing electronic diaries, we expanded this investigation. Variables were identified by their association with subsequent seizure using logit-normal random effects models fit by maximum likelihood. Nineteen subjects with localization-related epilepsy kept e-diaries for 12–14 weeks and reported 244 eligible seizures. In univariate models, several mood items and ten premonitory features were associated with increased odds of seizure over 12 h. In multivariate models, a 10-point improvement in total mood decreased seizure risk by 25% (OR 0.75, CI 0.61–0.91, p = 004) while each additional significant premonitory feature increased seizure risk by nearly 25% (OR 1.24, CI 1.13–1.35, p < 001) over 12 h. Pre-ictal changes in mood and premonitory features may predict seizure occurrence and suggest a role for behavioral intervention and pre-emptive therapy in epilepsy.     

Should we treat patients with impaired consciousness and periodic patterns on EEG?

PurposeThe significance of periodic EEG patterns in patients with impaired consciousness is controversial. We aimed to determine if treating these patterns influences clinical outcome.MethodWe studied all patients who had periodic discharges on their EEG recordings from January 2007 to December 2009. Patients with clinical seizures within the preceding 24 h, or with unequivocal electrographical seizure activity were excluded. Logistic regression was performed to analyze for factors associated with (a) mortality (b) functional status (c) resolution of EEG pattern.ResultsOf the 4246 patients who had EEG, 111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted analysis, higher mortality was associated with acute symptomatic etiology (OR 17.74, 95% CI 1.61–196.07, p = 0.019), and presence of clinical seizures (OR 4.73, 95% CI 1.10–20.34, p = 0.037). For each unit decrement of GCS, the odds of inpatient mortality and a poorer functional state on discharge increased by 23% (95% CI 7–37%, p = 0.009) and 33% (95% CI 9–51%, p = 0.011) respectively. Administration of abortive therapy was an independent risk factor for poorer functional status on discharge (adjusted OR 41.39, 95% CI 2.88–594.42, p = 0.006), while patients with history of pre-existing cerebral disease appeared more likely to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI 1.40–17.86, p = 0.013).ConclusionTreatment of periodic EEG patterns does not independently improve clinical outcome of patients with impaired conscious levels. Occurrence of seizures remote to the time of EEG and lower GCS scores independently predict poor prognoses.     

The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy

BackgroundThe mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism.MethodsForty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n = 21), while the other half received low-output (active control) stimulation (n = 20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires.ResultsRegarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p = 0.002) and correlated significantly with improvement of mood (τ = − 0.39, p = 0.037) and seizure frequency reduction (τ = − 0.33, p < 0.01). No significant changes were found between high- and low-output groups regarding seizure frequency.ConclusionVagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.     

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.     

Vagus nerve stimulation for medically refractory absence epilepsy

PurposeA proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population.MethodsPatients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale.ResultsNine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5 ± 60.3% (1-sided p-value for paired t-test = 0.04), with a 50% responder rate of 55.6%.ConclusionVNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy.