Pharmacological outcomes in newly diagnosed epilepsy

The response to antiepileptic drugs (AEDs) has been examined in 780 adult and adolescent patients with newly diagnosed epilepsy presenting with a range of seizure types and epilepsy syndromes over a 20-year period. Carbamazepine (CBZ, n=312), sodium valproate (VPA, n=315), and lamotrigine (LTG, n=249) were the most common AEDs prescribed as monotherapy. More patients with localization-related epilepsies became seizure free with LTG (63%) than with CBZ (45%, P=0.006) or VPA (42%, P=0.006). For idiopathic generalized epilepsies a greater proportion of patients achieved control with VPA (68%) than with CBZ (31%) or LTG (45%). In particular, more patients with juvenile myoclonic epilepsy responded to VPA (75%) compared with LTG (39%, P=0.014). Seizure freedom was achieved with modest or moderate daily doses (median CBZ 400mg, VPA 1000 mg, (LTG) 150 mg) of all three AEDs in the majority of patients achieving remission. Time to first seizure did not differ among these three drugs when given as first treatment. Adverse effects leading to withdrawal were more frequent with CBZ (16%) than with VPA (7%, P=0.03) or LTG (7%, P=0.018). In patients failing initial monotherapy, response to a combination of two AEDs (27%) was not different from that with alternative monotherapy (32%). The majority of patients with newly diagnosed epilepsy responding to treatment did so rapidly and completely with moderate doses of AEDs, with no differences in time to first seizure.     

Interictal Cardiovascular Autonomic Responses in Patients with Epilepsy

Summary: Purpose: To evaluate the interictal autonomic nervous system function in 84 patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy, and 47 patients receiving long-term carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure disorder. Methods: We assessed autonomic control of the cardiovascular regulatory system, by standardized cardiovascular reflex tests measuring changes in heart rate (HR) and blood pressure (BP) at rest and after certain stimuli. Results: The HR and BP responses were similar to those of control subjects in patients with newly diagnosed epilepsy. However, HR variation during normal breathing and maximum systolic BP increase in isometric work were diminished in patients, who had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time. Diminished HR responses to the Valsalva maneuver were noted in patients receiving CBZ as monotherapy and during deep breathing in patients receiving CBZ combined with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses in isometric work. When analyzed in relation to epilepsy type, suppressed HR responses in normal breathing were associated with primary generalized epilepsy (PGE), whereas diminished BP responses in isometric work were associated with partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1 patient receiving long-term CBZ monotherapy for partial epilepsy had two abnormal cardiovascular response test results. Conclusions: Our results show that cardiovascular responses mediated by both the parasympathetic and sympathetic nervous system are diminished in patients with epilepsy. However, the changes appear to be clinically significant in only a few of them and appear to be associated with CBZ medication. Further studies are needed to detect the underlying complex interactions and clinical significance of autonomic nervous system dysfunction in patients with epilepsy.     

Cognition and health-related quality of life in a well-defined subgroup of patients with partial epilepsy

To investigate the extent and nature of the objective and subjective cognitive deficits and health-related quality of life (HRQOL) in adult outpatients with relatively well-controlled partial epilepsy without symptomatic aetiology, who were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of the epilepsy history and medication on various cognitive functions and the HRQOL. 56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy were compared with 56 age-, gender-, and education-matched healthy controls. Patients were tested on attention, memory, speed of information processing, and executive functioning. Questionnaires aimed at measuring self-perceived cognitive functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were used to compare the two groups. Linear regression analysis was performed to identify the epilepsy and medication-related factors that are associated with cognitive functioning and HRQOL. Patients scored lower on measures of attention (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00). Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical functioning was unaffected. These patients also expressed reductions in mental functioning as indicated by a low self-perceived cognitive functioning (P = 0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency, localisation, years on CBZ, and CBZ dosage were not related to cognitive functioning or HRQOL. Patients with partial epilepsy, even when able to maintain regular jobs, have impaired cognition and HRQOL that cannot be attributed to their epilepsy history or CBZ dosage or years of CBZ intake. Therefore, physicians should be more aware of their cognition and HRQOL, in addition to the antiepileptic drug regime. Received: 16 March 2001, Received in revised form: 10 July 2001, Accepted: 16 July 2001     

Factors predictive of outcome in childhood epilepsy

To identify early predictive factors of outcome in childhood epilepsy, the case records of all children with new-onset epilepsy presenting to a single neurology practice over a 10-year interval were reviewed. Only children with more than 2 years of follow-up were included. Cox regression analysis was used to identify factors predictive of remission (successful cessation of medication). One hundred ninety-six children (mean age 7.6 +/- 3.7 years at first seizure, mean follow-up 55 +/- 30 months) were identified. Ninety-eight of 196 children (50%) had an idiopathic epilepsy, 63 of 196 (32.1%) had cryptogenic epilepsy, and 35 of 196 (17.9%) had remote symptomatic epilepsy. At final assessment, 52.6% were in remission, 12.8% had a poor outcome (recurrent seizures on therapeutic antiepileptic drug levels within 6 months prior to the final assessment), and 6.9% were intractable (more than one seizure/month over 1 year with failure of three or more anticonvulsants). One year after initiating treatment, factors associated with a lower probability of remission included seizure recurrence in the 6- to 12-month interval after therapy initiation (hazard ratio 0.24), multiple seizure types (hazard ratio 0.40), and mental retardation at onset (hazard ratio 0.19). Factors predictive of a poor outcome included seizure recurrence in the 6- to 12-month interval after therapy initiation (odds ratio 21.6), more than one seizure type (odds ratio 8.9), and global developmental delay at onset (odds ratio 8.9). Factors predictive of intractability included multiple seizure types (hazard ratio 6.5), mental retardation at onset (hazard ratio 7.2), and seizure recurrence in the first 6 to 12 months of treatment (hazard ratio 70). It appears that response in the first 6 to 12 months on antiepileptic medication is predictive of outcome. Clinical features of the underlying epilepsy and concurrent neurologic conditions were independently associated with intractability and a lower probability of remission.     

Valproate in children with newly diagnosed idiopathic generalized epilepsy

Holland KD, Monahan S, Morita D, Vartzelis G, Glauser TA. Valproate in children with newly diagnosed idiopathic generalized epilepsy.
Acta Neurol Scand: 2010: 121: 149–153.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Sparse information on dose–response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE. Materials and methods – Effect of initial valproate monotherapy and doses associated with seizure freedom were examined in consecutive children with IGE identified from a New Onset Seizure Clinic. Results – Of 84 patients identified, 48 (57%) became seizure‐free on valproate monotherapy and another 10 patients became seizure‐free but discontinued VPA because of adverse effects. The mean dose in seizure‐free children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25 mg/kg/day. Conclusions – Half of children became seizure‐free on valproate monotherapy and did so at modest doses.     

Early versus late remission in a cohort of patients with newly diagnosed epilepsy

Purpose:  To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission.
Methods:  Children and adults with previously untreated epilepsy from two Italian tertiary centers (Monza, Bari) were the study population. All patients received monotherapy at treatment start; drug choice and schedule were left to the physician's judgment. A retrospective audit was performed and the following prognostic predictors were identified: age, gender, putative etiology, first electroencephalography (EEG) record, neurologic and psychiatric examination, disease duration at diagnosis, seizure type(s) and number prior to starting treatment, epilepsy syndrome, and first antiepileptic drug. Early remission was defined by 2-year seizure control immediately after treatment start. Late remission was defined by 2-year seizure control achieved at least 24 months after treatment start. Prognostic predictors were assessed by logistic regression analysis, adjusting for age, gender, and center.
Results:  One hundred seventy-four women and 178 men (mean age 31.5 years) were included and followed for 2399.6 person-years. The cumulative time-dependent probability of 2-year remission was 56.3% at 2 years after treatment start, and 62.6, 69.4, and 79.5% at 3, 5, and 10 years. One hundred fifteen patients (23.0%) achieved early remission and 38 patients (10.8%) achieved late remission. The interaction between partial seizures and number of seizures prior to treatment was the only independent predictor of late remission.
Discussion:  The course of epilepsy and the chance of remission are together a complex and dynamic process, possibly explained by the diversity of the mechanisms underlying drug response and the use of an increasing number of drugs.     

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta‐analysis

Second and third generation AEDs have been directly compared to controlled‐release carbamazepine (CBZ‐CR) as initial monotherapy for new‐onset focal epilepsy. Conversely, no head‐to‐head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta‐analysis (NMA). Randomized, double‐blinded, parallel group, monotherapy studies comparing any AED to CBZ‐CR in adults with newly diagnosed untreated epilepsy with focal‐onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment‐emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ‐CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR‐CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6‐ and 12‐month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ‐CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ‐CR (OR 0.659, 95% CrI 0.428‐0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ‐CR     

Two-year remission and subsequent relapse in children with newly diagnosed epilepsy

PURPOSE: Although remission is the ultimate measure of seizure control in epilepsy, and epilepsy syndrome should largely determine this outcome, little is known about the relative importance of syndrome versus other factors traditionally examined as predictors of remission or of relapse after remission. The purpose of this study was to examine remission and relapse with respect to the epilepsy syndrome and other factors traditionally considered with respect to seizure outcome. METHODS: A prospectively identified cohort of 613 children with newly diagnosed epilepsy was assembled and is actively being followed to determine seizure outcomes. Epilepsy syndrome and etiology were classified at diagnosis and again 2 years later. Remission was defined as 2 years completely seizure-free, and relapse as the recurrence of seizures after remission. Multivariable analysis was performed with the Cox proportional hazards model. RESULTS: Five hundred ninety-four of the original 613 children were followed > or = 2 years (median follow-up, 5 years). Remission occurred in 442 (74%), of whom 107 (24%) relapsed. On multivariable analysis, idiopathic generalized syndromes and age at onset between 5 and 9 years were associated with a substantially increased remission rate, whereas remote symptomatic etiology, family history of epilepsy, seizure frequency, and slowing on the initial EEG were associated with a decreased likelihood of attaining remission. Young onset age (<1 year) and seizure type were not important after adjustment for these predictors. Relapses occurred more often in association with focal slowing on the initial EEG and with juvenile myoclonic epilepsy. Benign rolandic epilepsy and age at onset <1 year were associated with markedly lower risks of relapse. About one fourth of relapses were apparently spontaneous while the child was taking medication with good compliance, and more than half occurred in children who were tapering or had fully stopped medication. CONCLUSIONS: A large proportion of children with epilepsy remit. Symptomatic etiology, family history, EEG slowing, and initial seizure frequency negatively influence, and age 5-9 years and idiopathic generalized epilepsy positively influence the probability of entering remission. Factors that most influence relapse tend to be different from those that influence remission.     

The effect of antiepileptic drug therapy on antioxidant enzyme activity and serum lipid peroxidation in young patients with epilepsy

Changes in antioxidant defense mechanisms and the resulting increased lipid peroxidation are involved in the pathogenesis of epilepsy. Research findings concerning the effect of antiepileptic therapies on these processes are discordant. The aim of our study was to estimate, firstly, the activity of the following antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R), and secondly, malondialdehyde (MDA) serum concentration in children and adolescents newly diagnosed with epilepsy and receiving either carbamazepine (CBZ) or valproate (VPA) monotherapy, or polytherapy. The study group included 90 young patients with epilepsy, aged 6 months to 20 years. In 22 patients epilepsy was newly diagnosed; CBZ monotherapy was administered to 16 patients, VPA monotherapy--to 25, and polytherapy--in 27 cases. The control group consisted of 61 non-epileptic patients aged 4-17 years. SOD, GSH-Px and GSSG-R activities and MDA concentration were measured using spectrophotometry. SOD activity was decreased in newly diagnosed epileptic children receiving VPA or CBZ monotherapy (p < 0.05), or polytherapy (p < 0.01) in comparison to relevant levels in non-epileptic patients. GSH-Px activity was increased in all the patients, but significantly in those receiving polytherapy (p < 0.05). While in patients newly diagnosed with epilepsy no change in GSSG-R activity was found, its level was slightly lower both in those receiving VPA monotherapy and polytherapy, but increased in those with CBZ monotherapy. MDA concentration was elevated in all the epileptic patients, significantly (p < 0.05) both in VPA monotherapy and in polytherapy, while insignificantly--in newly diagnosed epilepsy and in CBZ monotherapy. Our results indicate that in the serum of children and adolescents with epilepsy the oxidants-antioxidants balance is modified by antiepileptic therapy.     

Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood

PurposeTo determine long-term outcome in a cohort of children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS).Methods29 children with BECTS were included in the Dutch Study of Epilepsy in Childhood. Each child was followed for 5 years, and subsequently contacted 12–17 years after enrolment to complete a structured questionnaire. Twenty children had typical BECTS, nine had atypical BECTS (age at onset <4 years, developmental delay or learning difficulties at inclusion, other seizure types, atypical EEG abnormalities).ResultsMean age at onset of epilepsy was 8.0 years with slight male preponderance. Most common seizure-types before enrolment were generalized tonic–clonic seizures (GTCS) and simple partial seizures; in 86% of the children seizures occurred during sleep. After 12–17 years, 96% had a terminal remission (TR_F) of more than 5 years and 89% of more than 10 years. Mean duration of epilepsy was 2.7 years; mean age at reaching TR_F was 10.6 years. Many children (63%) had experienced one or more (secondary) GTCS. Antiepileptic drugs were used by 79% of the children with a mean duration of 3.0 years. None of the children seemed to have developed learning problems or an arrest of cognitive development during follow-up. No significant differences were observed in patient characteristics or outcome between children with typical BECTS and children with atypical BECTS.ConclusionsAll children in our cohort, both those with typical and atypical BECTS, had a very good prognosis with high remission rates after 12–17 years. None of the predictive factors for disease course and outcome observed in earlier studies (other seizure types, age at onset, multiple seizures at onset) were prognostic in our cohort.     

A population-based study of long-term outcomes of cryptogenic focal epilepsy in childhood: cryptogenic epilepsy is probably not symptomatic epilepsy

Purpose: To compare long‐term outcome in a population‐based group of children with cryptogenic versus symptomatic focal epilepsy diagnosed from 1980 to 2004 and to define the course of epilepsy in the cryptogenic group. Methods: We identified all children residing in Olmsted County, MN, 1 month through 17 years, with newly diagnosed, nonidiopathic focal epilepsy from 1980 to 2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long‐term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings: Of 359 children with newly diagnosed epilepsy, 215 (60%) had nonidiopathic focal epilepsy. Of these, 206 (96%) were followed for >12 months. Ninety‐five children (46%) were classified as symptomatic. Median follow‐up from diagnosis was similar in both groups, being 157 months (25%, 75%: 89, 233) in the cryptogenic group versus 134 months (25%, 75%: 78, 220) in the symptomatic group (p = 0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long‐term outcome was significantly better in those with cryptogenic versus symptomatic etiology (intractable epilepsy at last follow‐up, 7% vs. 40%, p < 0.001; seizure freedom at last follow‐up, 81% vs. 55%, p < 0.001). Of those who achieved seizure freedom at final follow‐up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p = 0.01). One‐third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure‐free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group. Significance: More than half of childhood nonidiopathic localization‐related epilepsy is cryptogenic. This group has a significantly better long‐term outcome than those with a symptomatic etiology, and should be distinguished from it.     

A population‐based study of long‐term outcome of epilepsy in childhood with a focal or hemispheric lesion on neuroimaging

Purpose: To evaluate long‐term seizure outcome in children with epilepsy and a focal or hemispheric neuroimaging abnormality. Methods: All children (<18 years and residing in Olmsted County, Minnesota) with new‐onset epilepsy diagnosed between 1980 and 2004 and a single focal lesion on neuroimaging were identified by review of the Rochester Epidemiologic Project database. Outcomes were divided into three categories: (1) seizure freedom for 1 or more years at last follow‐up, (2) ongoing seizures but not medically intractable epilepsy, and (3) medically intractable epilepsy or undergoing epilepsy surgery. We also evaluated the proportion who achieved seizure control without surgical intervention and whether lesion type predicted intractability. Key Findings: Of the 359 children with newly diagnosed epilepsy, 37 (10%) had a focal or hemispheric lesion on neuroimaging. Median age of diagnosis was 89 months (25th percentile 26 months, 75th percentile 142 months) and at follow‐up was 137 months (25th percentile 95 months, 75th percentile 211 months). Eighty‐three percent of children with malformations of cortical development, 67% with mesial temporal sclerosis, 33% with encephalomalacia, and 50% with vascular malformations had intractable epilepsy at follow‐up or underwent resective surgery for medically intractable epilepsy. Among the different etiologies, presence of encephalomalacia predicted the lowest likelihood of medical intractability or undergoing surgery (p < 0.01). At final follow‐up, 24 (65%) of our entire cohort was seizure free. Following surgery, seizure freedom was achieved in 80% with mesial temporal sclerosis, 67% with encephalomalacia, 67% with vascular malformation, and 50% with malformations of cortical development. There was no statistically significant difference between the different etiologies on neuroimaging and seizure freedom after surgery. Twelve children (32%) achieved seizure freedom with medical management alone. Significance: Focal lesions on neuroimaging confer a high risk of medical intractability among children with new‐onset epilepsy. However, 32% of this cohort achieved seizure remission with medical management alone, including 58% with encephalomalacia and 33% with mesial temporal sclerosis.     

Efficacy and tolerability of levetiracetam in children younger than 4 years: a retrospective review

PURPOSE: To review our experience of the efficacy and tolerability of levetiracetam (LEV) in children younger than 4 years. METHODS: We used retrospective chart review to identify 122 children with seizures who were younger than 4 years and followed for >or=6 months. Efficacy was evaluated on the basis of the occurrence and durability of seizure remission. Tolerability was based on parent- and patient-reported side effects. RESULTS: Seventy (57%) subjects achieved seizure remission, and 52 (43%) did not. In univariate analysis, those achieving seizure remission were more likely to have partial epilepsy, require lower maintenance doses of LEV, and have fewer than two seizures per month at initiation of the medication. Only seizure frequency at initiation of LEV remained significant in multivariate analysis. The median duration of seizure freedom (8.9 month) was not influenced by age, epilepsy type, gender, or pretreatment seizure frequency. The dose of LEV was the only significant predictor of the duration of seizure remission, with longer duration of seizure remission seen in those taking <30 mg/kg/day compared with those taking > 30 mg/kg/day (median, 12.8 months vs. 3 months; p<0.0001). Side effects of LEV occurred in 34% of subjects but required discontinuation in only 16%, most commonly because of behavioral disturbances. CONCLUSIONS: LEV is an effective medication in children younger than 4 years and at doses lower than previously reported. It also well tolerated, suggesting that it represents an important option for the treatment of epilepsy in this age group.     

新型和传统抗癫痫药治疗新诊断癫痫患者的评价

目的评价新型和传统抗癫痫药(AEDs)单药治疗新诊断癫痫患者的疗效及安全性。方法前瞻性收集143例新诊断癫痫患者,分为卡马西平(CBZ)、丙戊酸钠(VPA)、托吡酯(TPM)和拉莫三嗪(LTG)治疗组,其中CBZ用于癫痫部分性发作,VPA用于癫痫全面性发作,而TPM和LTG用于各种类型癫痫发作,至少观察1年。采用生存分析Kaplan-Meier法比较治疗后癫痫初次发作时间、治疗失败时间,同时比较各组患者达"6月、1年无发作"比例和药物不良反应。结果 4组AEDs单药治疗后至癫痫初次发作时间、治疗失败时间的差异均无统计学意义(P0.05);CBZ、VPA、TPM和LTG组"6月无发作"率分别为80%、78%、87.9%、63.3%(均P0.05);"1年无发作"率分别为70%、66%、66.7%、50%(均P0.05)。TPM组不良反应率为63.3%,高于CBZ组(20%)、VPA组(24%)(均P0.01),而LTG组不良反应率为16.7%,与CBZ、VPA组相当(均P0.05)。结论从疗效和安全性综合考虑,新型AEDs治疗癫痫并不优于传统AEDs,其中TPM轻、中度不良反应还明显高于传统AEDs。     

Conversion from carbamazepine or oxcarbazepine to topiramate in adolescents and adults with epilepsy

Objective – To explore effectiveness, tolerability and changes in quality of life in patients with epilepsy converting to topiramate (TPM) from carbamazepine (CBZ) or oxcarbazepine (OXC) due to insufficient effectiveness and/or tolerability. Methods – A multicenter, open‐label, non‐interventional trial was used to examine patients (≥ 12 years) with epilepsy, changing to TPM monotherapy from baseline mono‐ or combination therapy with CBZ or OXC. TPM was added to the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1–2 weeks, until a final dose between 50 and 200 mg/day was reached. On the basis of clinical judgment, the treating physician decided whether or not the existing AED treatment with CBZ or OXC could then be withdrawn. Type and number of seizures, preferred TPM dose, quality of life (QOLIE‐10 questionnaire), subjective perception of improvement and adverse events (AE) were documented. Results – 140 patients (53.5% women, mean age 47 years) decided to switch to TPM due to insufficient effectiveness (75% of patients) and/or poor tolerability (80%) of the CBZ/OXC treatment. Average duration of follow‐up was 24 weeks with an overall discontinuation rate of 19.3%, mainly due to AEs (12.1%). At study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/day. A seizure reduction of ≥ 50% was achieved in 91% of patients in the last scheduled period (weeks 12–26); 62% of patients entering that period remained seizure free. Quality of life at endpoint improved significantly when compared with baseline for all domains of QOLIE‐10 (P < 0.001). Most frequent AEs (reported by ≥ 5% of patients) were paresthesia (9.3%), weight loss (7.9%), convulsions (5.7%) and memory disorders (5.0%). Conclusion – In patients with epilepsy, previously not satisfactorily treated with CBZ or OXC, conversion to TPM may result in an improvement in seizure control as well as in quality of life.     

MEG predicts outcome following surgery for intractable epilepsy in children with normal or nonfocal MRI findings

PURPOSE: To identify the predictors of postsurgical seizure freedom in children with refractory epilepsy and normal or nonfocal MRI findings. METHODS: We analyzed 22 children with normal or subtle and nonfocal MRI findings, who underwent surgery for intractable epilepsy following extraoperative intracranial EEG. We compared clinical profiles, neurophysiological data (scalp EEG, magnetoencephalography (MEG) and intracranial EEG), completeness of surgical resection and pathology to postoperative seizure outcomes. RESULTS: Seventeen children (77%) had a good postsurgical outcome (defined as Engel class IIIA or better), which included eight (36%) seizure-free children. All children with postsurgical seizure freedom had an MEG cluster in the final resection area. Postsurgical seizure freedom was obtained in none of the children who had bilateral MEG dipole clusters (3) or only scattered dipoles (1). All five children in whom ictal onset zones were confined to < or = 5 adjacent intracranial electrodes achieved seizure freedom compared to three of 17 children with ictal onset zones that extended over >5 electrodes (p = 0.002). None of six children with more than one type of seizure became seizure-free, compared to eight of 16 children with a single seizure type (p = 0.04). Complete resection of the preoperatively localized epileptogenic zone resulted in seizure remission in 63% (5/8) and incomplete resections, in 21% (3/14) (p = 0.06). Age of onset, duration of epilepsy, number of lobes involved in resection, and pathology failed to correlate with seizure freedom. CONCLUSIONS: Surgery for intractable epilepsy in children with normal MRI findings provided good postsurgical outcomes in the majority of our patients. As well, restricted ictal onset zone predicted postoperative seizure freedom. Postoperative seizure freedom was less likely to occur in children with bilateral MEG dipole clusters or only scattered dipoles, multiple seizure types and incomplete resection of the proposed epileptogenic zone. Seizure freedom was most likely to occur when there was concordance between EEG and MEG localization and least likely to occur when these results were divergent.     

An observational study of first-line valproate monotherapy in focal epilepsy

The objective of this multinational open-label, prospective study was to collect, under naturalistic conditions, data on the effectiveness and tolerability of first-line monotherapy with valproate in subjects newly or recently diagnosed with focal onset epilepsy. Patients were treated with sustained release sodium valproate. Seizure control and occurrence of adverse events were assessed after 6 months. Around 1192 adults and 792 children were included. The mean daily valproate dose was 683 mg in children and 987 mg in adults. The retention rate at 6 months was 90.0%. At this time, 77% of subjects were seizure free (83.7% of children and 72.7% of adults). Adverse events possibly related to treatment were observed in 10.2% of subjects, leading to treatment modification for 1.7%. The most common adverse events were weight gain, gastro-intestinal, neurological and skin disorders. Sustained release sodium valproate is effective and shows acceptable tolerability as first-line monotherapy in focal onset epilepsy.     

Pharmacological outcomes in older people with newly diagnosed epilepsy

BACKGROUND: Old age is the most common time in life to develop epilepsy. Despite this, there are few published data exploring pharmacological outcomes in this population. METHODS: We analyzed outcomes in 117 older patients (median age, 73; range, 65-92) for whom localization-related epilepsy was newly diagnosed and treatment begun at a single center over a 20-year period. RESULTS: Seventy-three (62%) patients became seizure-free for at least 12 months on their first AED, with 30 (26%) failing to respond and 14 (12%) not tolerating the treatment. Following pharmacological manipulation, 93 (79%) patients attained remission, 87 (93%) on monotherapy and 6 (7%) on duotherapy. No individual AED was more likely to confer seizure freedom than any other. Patients attaining remission were more likely to have had fewer pretreatment seizures (P=0.0078) than those who did not obtain full seizure control. CONCLUSION: The prognosis in epilepsy may be better in older than younger people, perhaps reflecting lower lesional epileptogenicity and genetic predisposition.     

Prognosis of Epilepsy in Newly Referred Patients: A Multicenter Prospective Study of the Effects of Monotherapy on the Long-Term Course of Epilepsy

Summary: A cohort of 280 previously untreated epilepsy subjects (159 men and 121 women aged 2–81 years) recruited in 14 Italian centers were treated with antiepileptic drug (AED) monotherapy and followed for a median period of 48 months to investigate the rates of seizure remission (i.e., complete control), in general and with reference to various prognostic factors. The cumulative probability of achieving 1-year remission was 62% by 1 year after onset of treatment, 81% by 2 years, 92% by 3 years, and 98% by 5 years. The corresponding figures for 2- and 3-year remission at 5 years were 92 and 78%, respectively. Sixty-two patients (22.1%) had no remission period with monotherapy. Remission rates were significantly lower among patients with two or more seizure types and were inversely correlated to the number of seizures before treatment. The rate of seizure relapses during the first year of follow-up appear to correlate to the risk of developing refractory epilepsy (i.e., with no remission).     

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center

ObjectiveThis study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom.MethodsThis study included 61 children aged between 2 and 18 years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom.ResultsOf the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p < 0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia.SignificanceResective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.