Effects of levetiracetam on seizure frequency and neuropsychological impairments in children with refractory epilepsy with secondary bilateral synchrony

PurposeIn epilepsy with continuous spikes and waves during slow sleep (CSWS), which is a representative epileptic syndrome of secondary bilateral synchrony (SBS), the urgent suppression of this electroencephalographic (EEG) abnormality may be necessary to prevent the progression of neuropsychological impairments. The purpose of this study was to determine the efficacy of levetiracetam (LEV) on SBS, seizure frequency, and neuropsychological impairments in children with refractory epilepsy.MethodsEleven (seven male and four female) patients with refractory epilepsy with SBS on EEG, aged between 4.7 years and 11.3 years, were included in this study. After a 3-month baseline period, the patients were given LEV at an initial dose of 10 mg/kg/day for the first week, followed at increments of 5 mg/kg/day every week, up to 20 mg/kg/day. The LEV dose was then adjusted up to a maximum of 60 mg/kg/day, according to the clinician's judgment. EEG recordings and clinical evaluations were performed every 3 months, focusing on SBS. The occurrence of SBS was then scored, and the relationship between the score and the response to LEV treatment was evaluated. In comparison with the baseline SBS frequency, the EEG response to LEV treatment was classified, and responders were identified as having a ≥50% reduction in SBS frequency. In addition, in comparison with the baseline seizure frequency, response to LEV treatment was classified. Responders were identified as patients with complete cessation (100% seizure control) and a response of ≥50% reduction in seizures. Furthermore, neuropsychological impairments such as hyperactivity, impulsiveness, and inattention were evaluated before and after LEV treatment.ResultsEight patients (72.7%) were considered responders. In addition, all eight patients were also considered responders for clinical seizures. Furthermore, 7 of 8 (87.5%) patients with response showed decreased hyperactivity and impulsivity after LEV administration.ConclusionsThe present data clearly indicate the usefulness of LEV in reducing both SBS on EEG and seizure frequency. LEV represents an important addition to the treatments available for refractory childhood epilepsies with SBS on EEG.     

Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types

This meta-analysis aimed to systematically collect and synthesize the current evidence regarding the efficacy and tolerability of levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types. We selected randomized-controlled trials (RCT) of LEV as an adjunctive therapy in epilepsy according to predefined criteria. Outcome measures included a ⩾50% reduction in seizure frequency, seizure freedom, and adverse events. Thirteen RCT were analyzed. Results showed that the efficacy of adjunctive LEV was superior to placebo both in achieving ⩾50% reduction in seizure frequency (pooled odds ratio [OR] 3.36, 95% confidence interval [CI] 2.78–4.07, Z = 12.46; p < 0.00001) and seizure freedom (pooled OR 4.72, 95% CI 2.96–7.54, Z = 6.50; p < 0.00001). The heterogeneity was mild (chi-squared = 12.28, I² = 2% in ⩾50% reduction in seizure frequency, and chi-squared = 0.49, I² = 0% in seizure freedom). Subgroup analysis suggested similar effects across different dosages in adults. The incidence of adverse reactions was not significantly different between the LEV group and the placebo group. The adverse events of relatively high incidence in the LEV group included somnolence, agitation, dizziness, asthenia, and infection. Incidence of serious adverse reaction such as rash and white blood cells and platelets decreasing was quite low. Adjunctive therapy with LEV was superior to placebo in reducing the frequency of seizures in patients with partial and idiopathic generalized epilepsy with effect in both adults and children, and demonstrated good tolerance in patients with epilepsy.     

Loss of the initial efficacy of levetiracetam in patients with refractory epilepsy

PurposeThe efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.MethodsWe enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.ResultsA total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P = 0.054). Based on Kaplan–Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.ConclusionThis study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.     

Rufinamide for refractory focal seizures: An open-label,multicenter European study

PurposeThe present study aimed to assess the efficacy and tolerability of rufinamide as adjunctive drug for the treatment of a large series of children, adolescents and adults with refractory cryptogenic or symptomatic focal epilepsy.MethodsPatients were recruited in a prospective, add-on, open-label treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care. Inclusion criteria were: (1) age 3 years or more; (2) diagnosis of cryptogenic or symptomatic focal epilepsy refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than one seizure per month in the last 6 months; (4) use of at least one other AED, but no more than three, at baseline; (5) informed consent from parents and/or caregivers.ResultsSixty-eight patients (40 males, 28 females), aged between 3 and 63 years (mean 19.9 years, median 16.0) ± SD 12.58, with cryptogenic (28 pts, 41.2%) or symptomatic focal epilepsy (40 pts, 58.8%), were recruited in the study. After a mean follow-up period of 10.4 ± 10.29 months, twenty-two patients (32.3%) had a 50–99% seizure reduction, and none became seizure-free. Twelve patients (17.6%) had a 25–49% seizure decrease, while in 30 (44.1%) seizure frequency was unchanged. A seizure worsening was reported in 5 patients (7.3%). A better response to rufinamide occurred in frontal lobe seizures (51.6%) and secondary generalized tonic–clonic seizures (50%).ConclusionRufinamide was effective against focal-onset seizures, particularly in the treatment of secondary generalized frontal lobe seizures.     

Levetiracetam efficacy in children with epilepsy with electrical status epilepticus in sleep

PurposeEpilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China.MethodsClinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n = 71) were retrospectively analyzed. The LEV dosage was 30–50 mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3–75 months after the start of LEV therapy.ResultsThirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a > 50% reduction in seizure frequency. Positive response on EEG was found during the first 3–4 months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients.ConclusionsLevetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.     

Prospective audits with newer antiepileptic drugs in focal epilepsy: Insights into population responses?

Despite the availability of a wide range of new antiepileptic drugs (AEDs), there is little evidence that their introduction has substantially altered outcomes. This paper reviews data from 5 consecutive prospective audits with new AEDs using similar methodology. Prospective audits with topiramate (TPM; n = 135), levetiracetam (LEV; n = 136), zonisamide (ZNS; n = 141), pregabalin (PGB; n = 135), and lacosamide (LCM; n = 160) were undertaken in treated patients with uncontrolled partial-onset seizures. Follow-up continued until one of four endpoints was reached: seizure freedom for ≥ 6 months on unchanged dosing; ≥ 50% reduction (responder) in seizure frequency on the highest tolerated dose compared with baseline; < 50% seizure frequency reduction (marginal response) compared with baseline in patients wishing to continue treatment with the new AED; or withdrawal due to lack of efficacy, side effects, or both. A greater proportion of seizure-free patients occurred with LEV (23.5%), LCM (21.9%), and TPM (20.7%) than with ZNS (12.8%) and PGB (10.4%). A higher percentage discontinued treatment with ZNS (41.8%) and PGB (50.4%) than with LEV (32.4%), TPM (31.1%), and LCM (22.5%). Most seizure-free patients responded to the new agent as first or second add-on (TPM 96%; LEV 97%; ZNS 89%; PGB 86%; LCM 97%) often at modest or moderate dosing (TPM 68%, ≤ 200 mg/day; LEV 63%, ≤ 1000 mg/day; ZNS 61%, ≤ 100 mg/day; PGB 86%, ≤ 300 mg/day; LCM 74%, ≤ 200 mg/day). With < 10% of patients discontinuing all AEDs due to lack of efficacy, tolerability was the major factor influencing the number of patients remaining on treatment. Lacosamide was the best (77% patients continued treatment), while PGB was the worst (50% continued treatment) tolerated AED. Overall, seizure freedom was achieved in < 25% of patients in each audit, mainly as a first or second add-on, with best tolerated AEDs producing a higher number of good outcomes. Seizures in very few patients with drug-resistant epilepsy, as defined by the International League Against Epilepsy task force, responded to any of the 5 newer AEDs. These data support the suggestion that the introduction of modern agents has not importantly impacted the outcomes in refractory epilepsy.     

Long-term levetiracetam treatment of epilepsy patients: Clinical audit

PurposeThe long-term efficacy and tolerability of levetiracetam (LEV) was analysed in 218 epilepsy patients. One hundred and ninety-nine patients were treated for at least 6 months. We evaluated LEV efficacy for all types of seizures together, and for simple partial, complex partial and secondary generalized seizures individually.ResultsA significant decrease in the number of seizures occurred after 6 months of treatment (p < 0.001). Mean seizure frequency (irrespective of type) before LEV was 19.2 a month. The mean monthly frequency at 6, 12, 24 and 36 months dropped to 12.7, 10.5, 9.7 and 7.1 seizures a month, respectively. The mean percentage reduction in seizures at these times was 45.7, 52.1, 59.1 and 64.2% and the number of responding patients was 51.3, 54.2, 59.8 and 62.2%. The number of patients completely seizure free was 18.6, 16.7, 15.2 and 16.2%. We found similar results in the last three categories for partial simple, complex and secondary generalized seizures individually. Side effects in 18.3% of patients caused treatment discontinuation in 6.4%. The most frequent were somnolence, moodiness and dizziness. The retention rate at 6, 12, 24 and 36 months was 0.848, 0.72, 0.62 and 0.5, respectively.ConclusionsLEV is effective and well tolerated for long-term treatment of epilepsy.     

Effectiveness and tolerability of zonisamide in children with epilepsy: A retrospective review

PurposeTo evaluate the effectiveness and tolerability of zonisamide in children with epilepsy.MethodRetrospective case note review of young people (less than 19 years) with epilepsy from three UK tertiary centres who received treatment with zonisamide and were followed up for a minimum of 12 months.ResultsFifty-seven children were included, aged 1.5–18.5 (median, 12) years. Thirty-three (57.9%) patients had generalised epilepsy, 21 (36.8%) focal epilepsy, and three (5.3%) a mixed, generalised and focal, epilepsy. Fifty-six of the 57 patients had been refractory to at least three previous antiepileptic drugs. The maintenance dose of zonisamide was [range (median)] 0.7–14 (5) mg/kg/day. The median duration of treatment for all patients was 12 (range 0.25–35) months. After 2 months of treatment, 51 patients remained on zonisamide, 18 (35.3%) of whom demonstrated a ≥50% reduction in seizure frequency. At the end of the follow-up period, there was a loss of effect for some patients. Thirteen (25.5%) of the 51 patients continued to demonstrate a ≥50% reduction in seizure frequency whilst two who had become seizure-free started having seizures again. Six (11.8%) had <50% reduction, twenty-four (47%) had no change, and eight (15.7%) had increasing seizures. Twenty-five (43.9%) patients reported unwanted effects although this contributed to the withdrawal of zonisamide in only ten (17.6%) patients.ConclusionsZonisamide appeared to be a reasonably effective and generally well-tolerated antiepileptic drug in a heterogeneous group of 57 children with poorly controlled epilepsy and provides another treatment option for children with refractory seizures.     

Six-month efficacy of the Ketogenic diet is predicted after 3 months and is unrelated to clinical variables

ObjectiveThe aim of this study was to evaluate the 6-month efficacy of a Ketogenic diet (KD) in children with drug-resistant epilepsy and to analyze the associated factors that affect the efficacy of a KD.MethodsEighty-seven pediatric patients with drug-resistant epilepsy who followed a KD for at least 6 months were included in this study. The efficacy of a KD was assessed based upon the seizure frequency, as recorded by parents and caregivers. The number of cases and the degree of efficacy in different age ranges were also considered. The effects of gender, age, seizure type, etiology, blood glucose and ketone levels, seizure frequency before the diet, and cognition on the length of time on a KD were analyzed.Results(1) There was no significant correlation between the length of time on a KD and efficacy (χ² = 2.31, P = 0.51). The 3-month efficacy of a KD was 51%, which did not further increase when the course was extended to 6 months. (2) There was a positive correlation between increased cognition and the efficacy of a KD after 3 months (γ = 0.31, P = 0.003). (3) The efficacy analysis of 3-month treatment with a KD revealed, with respect to seizure types, that there were 37 patients with multiple seizure phenotypes and 50 patients with a single seizure phenotype. The overall efficacy of a KD in the group with multiple seizure phenotypes was 61%. The efficacy of a KD was not statistically associated with a coexisting syndrome or a type of syndrome; however, the efficacy of a KD had a tendency to be increased in certain types of syndromes. The overall efficacy in the group with a single seizure phenotype was 87%, and the efficacy was not associated with seizure type. (4) The 3-month efficacy of a KD was not correlated with age, gender, etiology, blood glucose or ketone levels, or the seizure frequency before treatment.ConclusionAn observation time of 3 months is appropriate for assessing the efficacy of a KD in treating children with drug-resistant epilepsy. The factors that likely influence the efficacy of a KD are unclear, but our study suggests that incorporating more patient samples will help determine whether patients with certain syndromes can benefit from a KD.     

Vagus nerve stimulation in refractory epilepsy: New indications and outcome assessment

Although vagus nerve stimulation (VNS) is an effective alternative option for patients with refractory epilepsy unsuitable for conventional resective surgery, predictors of a better control of seizure frequency and severity are still unavailable. This prospective study reports on 39 patients, including 4 children affected by epilepsia partialis continua (EPC), who underwent VNS for refractory epilepsy. The overall seizure frequency outcome was classified into three groups according to reduction rate: ≥ 75%, ≥ 50%, and < 50%. Engel and McHugh classifications were also used. The median follow-up period was 36 months. A seizure reduction rate ≥ 50% or EPC improvement was observed in 74% of the patients. Twenty-one out of 35 cases (60%) resulted in Engel classes II and III. Outcome, as defined by the McHugh scale, showed a responder rate of 71%.These results suggest that younger patient age and focal or multifocal epilepsy are related to a better seizure control and cognitive outcome. Vagus nerve stimulation could also be considered as an effective procedure in severe conditions, such as drug-refractory EPC.     

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.     

Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: a multicenter open-label single-arm trial in Korean patients

ObjectiveTo evaluate the efficacy and safety of adjunctive zonisamide (ZNS) therapy in Korean adults with uncontrolled partial epilepsy.MethodsStudy patients had an average of at least one seizure per 4-week (averaged over a 12-week historical baseline) despite the use of one to three antiepileptic drugs. The starting dose of ZNS was 100 mg/day, and was increased to 200 mg/day after 2 weeks. During the 12-week maintenance period, the dose of ZNS was adjusted to 200–400 mg/day based on the physicians’ discretion. The global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated.ResultsA total of 121 patients were enrolled, of which 88 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 59.0%. The ≥50% and ≥75% responder rates were 57.3% and 38.5%, respectively. Seizure freedom over the treatment period was observed in 25 patients, but seizure freedom throughout the 16-week treatment period was attained in only 16 patients. On investigator's GES, 84 patients were considered improved, with 33 patients showing marked improvement. In QOLIE-31 scale, seizure worry improved significantly but emotional well-being deteriorated. Treatment-emergent adverse events (AEs) were reported in 80 patients. The most common AEs were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14.0%), nausea (13.2%), and weight loss (10.7%). Twenty-two patients discontinued the trial due to drug-related AEs.ConclusionsOur results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy, though efficacious, is associated with significant tolerability problems.     

Papel de la estimulación del nervio vago en el tratamiento de la epilepsia refractaria. Resultados clínicos e impacto en la calidad de vida

BackgroundVagus nerve stimulation (VNS) is used as a complementary therapy to pharmacological treatment in patients with refractory epilepsy. This study aims to evaluate the efficacy of VNS in reducing seizure frequency, severity, and duration; reducing the number of antiepileptic drugs administered; and improving patients’ quality of life.Material and methodsWe analysed the clinical progression of 70 patients with refractory epilepsy treated with VNS at Hospital Universitario de Alicante and Hospital Clínico de Valencia. Data were collected before and after the procedure. The difference in seizure frequency pre- and post-VNS was classified using the McHugh scale. Data were also collected on seizure duration and severity, the number of drugs administered, and quality of life.ResultsAccording to the McHugh classification, 12.86% of the patients were Class I, 44.29% were Class II, 40% were Class III, and the remaining 2.86% of patients were Class IV-V. A ≥ 50% reduction in seizure frequency was observed in 57.15% of patients. Improvements were observed in seizure duration in 88% of patients and in seizure severity in 68%; the number of drugs administered was reduced in 66% of patients, and 93% reported better quality of life.ConclusionsVNS is effective for reducing seizure frequency, duration, and severity and the number of antiepileptic drugs administered. It also enables an improvement in patients’ quality of life.     

Low Glycemic Index Treatment in pediatric refractory epilepsy: The first Middle East report

PurposeIntractable epilepsy is a challenging aspects of pediatric epilepsy. This study was conducted to determine the efficacy and tolerability of Low Glycemic Index Treatment (LGIT) in pediatric patients referred to a Children's Hospital in Iran with intractable epilepsy.MethodsWe studied 42 children with refractory epilepsy aged between 1.5 and 17 years of age, from October 2009 to April 2011 in the pediatric neurology department of Mofid Children's Hospital. Patient information on clinical status, seizure type, and baseline frequency, blood and urine biochemistry, neuro-imaging and the EEG were collected. LGIT was initiated on an outpatient basis and the diet was composed of 65% fat, 25% protein and 10% carbohydrate (40–60 g), and the glycemic index of foods was limited to below 50.Results84% of patients were categorized as having more than one seizure per day at study entry, with the remaining children as experiencing over one seizure per week. A greater than 50% seizure reduction was observed in 71.4% of the patients after the second week, in 73.8% at the end of the first month and in 77.8% at the end of the second month. In 30% of the patients a mild increase in blood urea nitrogen (BUN) was detected. The most important reasons for discontinuation of LGIT were restrictiveness, lack of satiation and excessive meat in this diet. No significant complications were observed during the administration of the diet.ConclusionLGIT is a safe and effective adjuvant antiepileptic therapy and may be used as an alternative to the ketogenic diet in conditions when this diet cannot be used.     

Measurement of levetiracetam drug levels to assist with seizure control and monitoring of drug interactions with other anti-epileptic medications (AEMs)

PurposeLevetiracetam (LEV) therapeutic range (20–40 mg/L) and potential drug interactions were assessed in people with epilepsy (PWE).MethodFifty-two PWE had LEV and concomitant medications [carbamazepine (CBZ); valproate (VPA); lamotrigine (LTG)] blood levels measured and compared to seizure activity. Lacosamide (LCM) levels were unavailable. Adopted therapeutic ranges were: 20–40 mg/L – LEV; 25–50 μmol/L – total CBZ; 6–13 μmol/L – free CBZ; 300–750 μmol/L – total VPA; 30–75 μmol/L – free VPA; and 40–60 μmol/L – LTG. Seizure-freedom was assessed and patients followed for almost two years.Results23 of 52 PWE (44%) used LEV monotherapy and 16/23 (70%) had ‘therapeutic’ LEV with 13/16 (81%) seizure-free. 29 of 52 (56%) used polytherapy and 16/29 (55%) had ‘therapeutic’ LEV with 7/16 (44%) seizure-free. 11 of 29 (38%) used CBZ: 4/11 (36%) had therapeutic mean LEV levels and 7/11 (64%) were seizure-free. Fourteen (48%) used VPA: 9/14 (64%) had therapeutic mean LEV levels and 8/14 (57%) were seizure-free. 13 of 29 (45%) used LTG: 8/13 (62%) had therapeutic mean LEV levels and 5/13 (38%) were seizure-free. LEV did not alter CBZ, but CBZ affected LEV. LEV elevated VPA free levels but not VPA total levels. Dosage/concentration was lowered with polytherapy.ConclusionLEV range (20–40 mg/L) assisted epilepsy management and anti-epileptic medication interactions were suggested with polytherapy thus possibly explaining the impaired efficacy of LEV with polytherapy.     

Characteristics of refractory vs. medically controlled epilepsy patients with obstructive sleep apnea and their response to CPAP treatment

Obstructive sleep apnea (OSA) commonly coexists with epilepsy, and treatment of OSA may decrease seizure frequency. However, it is unclear whether patients with medically refractory epilepsy have a higher incidence of OSA compared with well-controlled epilepsy patients and whether the two groups carry different risk factors.PurposeThis study aimed to investigate the presence of OSA in patients with refractory vs. well-controlled epilepsy and their associated risk factors. We also assessed the benefits of treatment of OSA with continuous positive airway pressure (CPAP) in refractory epilepsy patients.MethodsWe retrospectively reviewed data from patients who presented to the Jacobs Neurological Institute Comprehensive Epilepsy Center of University at Buffalo from 2007 to 2010.ResultsThere is a tendency for much higher incidence of OSA in our epilepsy population compared with the general population (15.2% vs. 4.41%). For patients with well-controlled epilepsy, older age, male gender, and higher seizure frequency were predictors of a diagnosis of OSA. However, in medically refractory epilepsy patients, diabetes and snoring predicted a diagnosis of OSA. Treatment of OSA with CPAP in refractory epilepsy patients improved their seizure control (p < 0.02).ConclusionThis study confirms that OSA is common in epilepsy patients and treatment of OSA can improve seizure control in medically refractory cases. Patients with refractory epilepsy who have diabetes are more likely to have OSA.     

Efficacy and safety of the ketogenic diet in Chinese children

ObjectiveTo evaluate the efficacy and safety of the ketogenic diet (KD) treatment of refractory childhood epilepsy in China and determine which children are more likely to respond.MethodsBetween 2004 and 2011, we prospectively enrolled 317 children with refractory epilepsy for the KD treatment in Shenzhen Children's Hospital and followed up for at least a year. Outcome was measured by seizure frequencies before and after the diet, change in anticonvulsant use and adverse effects. We also evaluated influences of different variables (starting age, duration of epilepsy and underlying conditions) on the outcome.ResultsIntent-to-treat analysis showed that after 3, 6 and 12 months, 62.8%, 42.0% and 24.3% remained on the diet, 35.0%, 26.2% and 18.6% showed >50% seizure reduction, including 20.8%, 13.6% and 10.7% seizure free, respectively. Starting age may influence efficacy. The ≥10 age group showed worse response than the <10 age group, though the difference was statistically significant (p = 0.039) at 3 month only. Other variables such as duration of epilepsy at the start of the diet, seizure types and aetiologies showed no significant influence on efficacy. Frequently reported complications included GI disturbance, food refusal and hypoproteinaemia.ConclusionsThe KD is a safe and efficacious therapy for intractable childhood epilepsy in Chinese children. The influence of age on efficacy is worth further investigation.     

A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment

PurposeThe objective of this work was to review systematically the efficacy and tolerability of perampanel (PER) in residential patients of an epilepsy center.MethodWe adopted an industry-independent noninterventional retrospective evaluation on the basis of the paper and electronic records complemented by personal information on the part of the treating neurologists. All patients (N = 26, 15 females, mean age: 30, range 21–55 years) started on PER from its introduction to the market in September 2012 until December 15th 2013 were included. Evaluation was carried out after 6, 12, and 24 months of PER treatment. Changes in seizure frequency were calculated as the number of seizures during three months on PER compared to a three-month baseline period. The Clinical Global Impression Scale served as an instrument to record changes in seizure intensity beyond numerical values. Adverse effects were documented by means of the Liverpool Adverse Events Profile.ResultsMost patients had structural or metabolic epilepsy, 2 patients suffered from Lennox-Gastaut syndrome, 2 from other symptomatic generalized epilepsy. All patients had grade III drug-resistant epilepsy. All patients had additional cognitive deficits of different degree.The retention rates were 61.5% after 6 months, 46.2% after 12 months, and 42.3% after 24 months. The responder rates were 11.5% after 6 months, 23.1% after 12 months, and 7.7% after 24 months. Partial responders (positive CGI and/or seizure reduction < 50%) included, the respective values were 26.9%, 38.5%, and 23.1%. Only 1 patient was seizure free at 12 months (but not at 24 months). A loss of efficacy in the second year of treatment was suspected but the decrease of the responder rate could also be ascribed to a number of different circumstances. Adverse effects in the psychiatric field like irritability, aggression, increased sensitivity, and suicidal ideation/behavior occurred in 50% of the patients. They were the main reason to discontinue PER.ConclusionsAfter one year of treatment PER showed reasonable efficacy in a particularly difficult-to-treat population. Psychiatric adverse effects forced discontinuation in many cases.     

Retention rate of pregabalin in drug-resistant epilepsy: 1-year follow-up, single-centre observation in 105 consecutive, adult patients

ObjectivesPregabalin (PGB) is a newer antiepileptic drug (AED) licensed as add-on treatment for partial epilepsy in adults. Efficacy and safety have been proven in several controlled clinical studies. These trials, however, only partially reflect clinical practice. Retention rate has been established as a marker for efficacy and safety of AEDs in long-term follow-up studies.MethodsWe evaluated the data of the first 105 patients treated with PGB at Bethel Epilepsy Centre, a tertiary referral centre for epilepsy. The patients were interviewed after 3, 6 and 12 months.Results105 adult patients (aged 38 ± 13 years) were treated with PGB, on average in combination with 2.1 AEDs (mean observation period 232 days). 76.2% had focal epilepsy, 19.0 multifocal epilepsy, and 3.8% epilepsy with both focal and generalised seizures. 40% continued PGB with the following outcome: 5.7% seizure-free for at least 1 month (4.8% for at least 3 months, 2.4% for at least 6 months; one of the seizure-free patients, however, had had epilepsy surgery during the observational period), 17.1% responders (≥50% reduction of seizure frequency but not seizure-free), 13.3% with unchanged or increased seizure frequency. Reasons for withdrawal were lack of efficacy (47.6%) or side-effects (12.7%).ConclusionsPGB is a new therapeutic option as add-on therapy for patients with highly refractory focal epilepsies although the therapeutic success that can be expected in this group of patients is limited.     

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.