Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Differential effects of antiepileptic drugs on neonatal outcomes.

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12 months old, but normalized by age 24 months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 min, but scores were near normal in all groups at 5 min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.

Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years.

OBJECTIVE: To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure. METHODS: The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5). RESULTS: Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills. CONCLUSIONS: Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.

Effects of breastfeeding in children of women taking antiepileptic drugs.

BACKGROUND: Breastfeeding is known to have beneficial effects, but there is concern that breastfeeding during antiepileptic drug (AED) therapy may be harmful to cognitive development. Animal and human studies have demonstrated that some AEDs can adversely affect the immature brain. However, no investigation has examined effects of breastfeeding during AED therapy on subsequent cognitive abilities in children. METHODS: The Neurodevelopmental Effects of Antiepileptic Drugs Study is an ongoing prospective multicenter observational investigation of long-term effects of in utero AED exposure on cognition. Between 1999 and 2004, we enrolled pregnant women with epilepsy who were taking a single AED (carbamazepine, lamotrigine, phenytoin, or valproate). We recently reported on differential AED effects on age 3 year cognitive outcomes. In this report, we focus on the effects of breastfeeding during AED therapy on age 3 cognitive outcomes in 199 children. RESULTS: A total of 42% of children were breastfed. IQs for breastfed children did not differ from nonbreastfed children for all AEDs combined and for each of the 4 individual AED groups. Mean adjusted IQ scores (95% confidence intervals) across all AEDs were breastfed = 99 (96-103) and nonbreastfed = 98 (95-101). Power was 95% to detect a half SD IQ effect in the combined AED analysis, but was inadequate within groups. CONCLUSIONS: This preliminary analysis fails to demonstrate deleterious effects of breastfeeding during AED therapy on cognitive outcomes in children previously exposed in utero. However, caution is advised due to study limitations. Additional research is needed to confirm this observation and extend investigations to other AEDs and polytherapy.

A water-soluble carbon monoxide-releasing molecule (CORM-3) lowers intraocular pressure in rabbits.

BACKGROUND: Carbon monoxide-releasing molecules (CORMs) are a novel group of substances that are capable of modulating physiological functions via the liberation of CO. AIMS: This study was undertaken to investigate the effects of CORM-3, a water-soluble CO-releasing agent, on two rabbit models of ocular hypertension. METHODS: Ocular hypertension was induced by injecting alpha-chymotrypsin in the rabbit eye. The dose-response effect of CORM-3 on IOP was assessed by topical administration of the drug (0.001, 0.01, 0.1 and 1%). Ocular hypertension was also obtained by weekly subconjunctival injection of betamethasone, and animals were treated topically with CORM-3. A group of animals in both models was treated with the inactive form of the drug (iCORM-3). RESULTS: CORM-3 induced a dose-dependent reduction in IOP in rabbits treated with alpha-chymotrypsin. A similar reduction in IOP was observed in rabbits with betamethasone-induced ocular hypertension treated with the drug. Treatment with the iCORM-3 had no effect on IOP in both models. CONCLUSIONS: Treatment with CORM-3 is associated with a reduction in IOP in two different rabbit models of ocular hypertension. These results support previous findings on the effect of haem oxygenase-derived CO on IOP and suggest a direct involvement of CO system in the regulation of ocular pressure probably through the modulation of aqueous humour dynamics.

Randomized dose-controlled study of topiramate as first-line therapy in epilepsy.

OBJECTIVES: To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design. MATERIALS AND METHODS: We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized. RESULTS: Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months. CONCLUSION: Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.

Improved tolerability and efficacy in epilepsy patients with extended-release carbamazepine.

The authors conducted a 3-month, prospective, open-label study assessing the effects of switching from immediate-release carbamazepine formulations to an equal total daily dose of carbamazepine extended-release capsules (CBZ-ERC) in adolescents and adults with epilepsy. Using validated, epilepsy-specific measures the authors found that switching to CBZ-ERC significantly improved patients' adverse events and quality-of-life measures. Switching to CBZ-ERC also improved seizure control.

Valproic acid blood genomic expression patterns in children with epilepsy - a pilot study.

OBJECTIVE: Valproic acid (VPA) is a commonly used anticonvulsant with multiple systemic effects. The purpose of this pilot study is to examine the blood genomic expression pattern associated with VPA therapy in general and secondly VPA efficacy in children with epilepsy. MATERIALS AND METHODS: Using oligonucleotide microarrays, gene expression in whole blood was assessed in pediatric epilepsy patients following treatment with VPA compared with children with epilepsy prior to initiation of anticonvulsant therapy (drug free patients). RESULTS: The expression of 461 genes was altered in VPA patients (n = 11) compared with drug free patients (n = 7), among which a significant number of serine threonine kinases were down-regulated. Expression patterns in children seizure free on VPA therapy (n = 8) demonstrated 434 up-regulated genes, many in mitochondria, compared with VPA children with continuing seizures (n = 3) and drug free seizure patients (n = 7). CONCLUSION: VPA therapy is associated with two significant and unique blood gene expression patterns: chronic VPA monotherapy in general and a separate blood genomic profile correlated with seizure freedom. These expression patterns provide new insight into previously undetected mechanisms of VPA anticonvulsant activity.

An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.

BACKGROUND: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population. METHODS: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate. RESULTS: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. CONCLUSION: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.

Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy.

OBJECTIVES: To compare topiramate (TPM) with investigator's choice of carbamazepine (CBZ) or valproate (VPA) for initial treatment in patients with newly diagnosed epilepsy. MATERIAL AND METHODS: In patients with epilepsy diagnosed within previous 3 months, investigators selected CBZ (600 mg/day) or VPA (1250 mg/day) as preferred therapy based on the patient's clinical presentation. Based on investigators' treatment choice, patients (n=613) were assigned to the CBZ or VPA treatment branch. Within each branch, patients were randomized to double-blind treatment with the traditional antiepileptic drugs (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. Patients continued double-blind treatment until exiting the study or until 6 months after last patient randomized. RESULTS: No statistically significant differences between fixed doses of TPM and CBZ or VPA were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment. TPM 100 mg/day was associated with the fewest discontinuations due to adverse events. CONCLUSION: In patients with newly diagnosed epilepsy, an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of CBZ and VPA.

Vagus nerve stimulation for partial seizures.

BACKGROUND: Vagus nerve stimulation (VNS) has recently been introduced as an adjunct for treating patients with seizures. The aim of this systematic review was to overview the current evidence for the effects of vagus nerve stimulation, when used as an adjunctive treatment for patients with drug-resistant partial epilepsy. OBJECTIVES: To determine the effects of VNS high-level stimulation compared to low-level (presumed subtherapeutic dose) stimulation. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, MEDLINE (January 1966 to October 2000) and The Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2000). SELECTION CRITERIA: Randomized, double-blind controlled trials of VNS comparing high and low stimulation paradigms. Studies in adults or children with drug-resistant partial seizures. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. MAIN RESULTS: Results of the overall efficacy analysis show that VNS stimulation using the high stimulation paradigm was significantly better than low stimulation. The overall OR (95% Confidence Interval (CI)) for 50% responders across all studies is 1.93 (1.1,3.3). This effect did not vary substantially and remained statistically significant for both the best and worst case scenarios. Results for the outcome "withdrawal of allocated treatment" suggest that VNS is well tolerated as no significant difference was found between the high and low stimulation groups, and withdrawals were rare. Statistically significant adverse effects associated with implantation (low versus baseline) were hoarseness, cough, pain and paresthesia. Statistically significant adverse effects associated with stimulation (high versus low) were hoarseness and dyspnea, suggesting the implantation is associated with hoarseness, but the stimulation produces additional hoarseness. REVIEWER'S CONCLUSIONS: VNS for partial seizures appears to be an effective and well tolerated treatment. Adverse effects of hoarseness, cough, pain, paresthesias and dyspnea are associated with the treatment but appear to be reasonably well tolerated as dropouts were rare. Typical central nervous system adverse effects of antiepileptic drugs such as ataxia, dizziness, fatigue, nausea and somnolence were not statistically significantly associated with VNS treatment.

Efficacy of levetiracetam: a review of three pivotal clinical trials.

Levetiracetam is a novel antiepileptic drug (AED) with favorable pharmacologic characteristics and demonstrated activity in improving seizure control. Three multicenter double-blind, placebo-controlled studies were conducted in 904 patients with refractory partial-onset seizures. Patients were required to have a minimum of two or four seizures per week (depending on the study) and were maintained on a stable regimen of one or two AEDs at baseline that was continued during the study period. Patients ranged in age from 14 to 70 years, with a mean age of approximately 37 years. After an 8- to 12-week baseline period, patients were randomized and had doses titrated upward every 2 weeks over a period of 4 weeks to a target dose of 1,000, 2,000, or 3,000 mg/day of levetiracetam or placebo. Treatment was continued for a 12- to 14-week evaluation phase followed by an optional open-label treatment phase. The treatment period consisted of the dose titration period combined with the evaluation period. The median percentage reduction in seizure frequency (over placebo) was calculated for each of the levetiracetam treatment groups over the entire treatment period. For all levetiracetam dose groups, in all studies, reduction in seizure frequency over placebo was statistically significant (p < or = 0.001). Median percentage reductions were 26.1% and 17.1% in the 1,000-mg/day groups (study 1 and study 2, respectively), 21.4% in the 2,000-mg/day group (study 2), and 30.1% and 23.0% in the 3,000-mg/day groups (study 1 and study 3, respectively). The percentage of patients achieving a > or = 50% reduction from baseline in seizure frequency compared with the treatment period was 37.1% and 20.8% in the 1,000-mg/day groups (study 1 and study 2, respectively), 35.2% in the 2,000-mg/day group (study 2), and 39.6% and 39.4% in the 3,000-mg/day groups (study 1 and study 3, respectively). These responder rates were significantly higher than those for placebo (p < 0.001 for all comparisons). Levetiracetam was generally well tolerated in all studies. Results from these three pivotal studies demonstrate that levetiracetam, as adjunctive therapy, is a safe and effective treatment for refractory partial-onset seizures in adults.

Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review.

OBJECTIVE: To undertake a systematic review and meta-analysis of placebo controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy. METHODS: We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for levetiracetam and remacemide. RESULTS: We found four trials (1023 patients) of levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61-3.79), respectively. There was evidence for increasing effect with increasing dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60) and 1.64 (1.02-2.62), respectively. CONCLUSIONS: These data suggest a useful effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable 'responder-withdrawal ratio' followed by zonisamide and oxcarbazepine.

Postictal language dysfunction in complex partial seizures: effect of contralateral ictal spread.

The authors report postictal language evaluation in patients monitored with bitemporal depth electrodes. Patients whose seizures began in the nondominant temporal lobe and propagated to the contralateral temporal lobe had a prolonged postictal language delay (PILD) with paraphasic errors compared with seizures that did not spread. Shorter propagation time was also associated with a longer PILD. Our study suggests that ictal involvement of the dominant temporal lobe is important in postictal language behavior.

Levetiracetam add-on for drug-resistant localization related (partial) epilepsy.

BACKGROUND: The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug. However, up to 30% develop refractory seizures, particularly those with partial seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as an add-on treatment for drug-resistant localization related (partial) epilepsy. OBJECTIVES: To evaluate the effects of levetiracetam on seizures, side effects, quality of life and cognition, when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2000). In addition, we contacted UCB SA (makers of levetiracetam) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of levetiracetam in patients with a drug-resistant localization related (partial) epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects; (d) cognitive effects; (e) quality of life. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Dose response was evaluated in regression models. MAIN RESULTS: Four trials (1023 patients) were included. All four trials had data for treatment withdrawal and side effect outcomes. Three trials (904 patients) had data for 50% or greater reduction in seizure frequency. Three trials (595 patients) had data for quality of life and cognitive outcomes. The overall Odds Ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in total seizure frequency outcome was 3.81 (2.78,5.22). Dose regression analysis shows clear evidence that levetiracetam reduces seizure frequency with an increase in efficacy with increasing dose of levetiracetam. Approximately 15% of patients taking 1000 mg and 20-30% of patients taking 3000 mg levetiracetam per day have a 50% or greater reduction in seizure frequency. Patients were not significantly more likely to have levetiracetam withdrawn, OR (95% CI) 1.25 (0.87,1.80). The following side effects were significantly associated with levetiracetam: dizziness 2.36 (1.21, 4.61) and infection 1.82 (1.05, 3.14) whereas accidental injury was significantly associated with placebo 0.55 (0.32, 0.93). Quality of life and cognitive effect outcomes suggest that levetiracetam has a positive effect on cognition and some aspects of quality of life. REVIEWER'S CONCLUSIONS: Levetiracetam reduces seizure frequency when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy, and seems well tolerated. Minimum effective and maximum tolerated doses have not been identified. The trials reviewed were of 16-24 weeks duration and results cannot be used to confirm longer term effects. Our results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes. Great care should also be taken with any attempt to apply these results to children.

Four-year incidence of psychogenic nonepileptic seizures in adults in hamilton county, OH.

In this retrospective study, the incidence of psychogenic nonepileptic seizures in Hamilton County, OH, between 1995 and 1998 was determined. The mean incidence of psychogenic nonepileptic seizures was 3.03/100,000, with the highest incidence in 1998 (4.6/100,000). Most patients with the diagnosis of psychogenic nonepileptic seizures were aged 25 to 45 years (4.38/100,000).

Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group.

The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.

Detection of epileptogenic focal cortical dysplasia by depth, not subdural electrodes.

Centers that perform presurgical epilepsy evaluations disagree on whether depth or subdural electrodes represent the optimal technique for invasive recording, especially in seizures originating outside the temporal lobe. A 13-year-old girl with a normal magnetic resonance imaging scan had unlocalized partial onset seizures, despite scalp and subdural grid ictal video/EEG recordings. Repeat video/EEG with depth electrodes showed a discrete site of continuous interictal spiking and seizure onset that was located 2-2.5 cm beneath the surface of the sensory cortex. The resected region showed focal cortical dysplasia and the patient had greater than 95% seizure frequency reduction at 3-year follow-up. We conclude that although subdural electrodes have many advantages when recording seizures outside the temporal lobes, depth electrodes may provide superior recordings when the epileptogenic region is beneath the cortical surface.

Directed forgetting deficits in patients with temporal lobe epilepsy: an information processing perspective.

Although mesial temporal lobe brain damage is frequently associated with memory loss, it is unclear whether the deficit results entirely from a disruption in the processing of relevant information or whether it also reflects interference from irrelevant information. Directed forgetting is one procedure that can be used, along with standard tests of memory, to investigate this distinction. Seventeen patients with a diagnosis of complex-partial seizures of temporal lobe origin and 17 healthy volunteers were compared on lexical decision, free recall, and recognition tests in a directed-forgetting paradigm. These tests created a memory profile to measure the influence of task relevant and irrelevant information in implicit and explicit memory. Compared with healthy volunteers, the patients were significantly impaired on the memory tasks overall [F(5,25) = 5.01, p < .01]. Specifically, directed forgetting in lexical decision and recognition both discriminated between the groups [stepdown F(1,26) = 6.84, eta 2 = .26, p < .05 and stepdown F(1,25) = 5.36, eta 2 = .13, p < .05, respectively]. The results suggest that interictal memory performance in temporal lobe epilepsy may be disrupted in part because of a deficit in the differential processing of task relevant and task irrelevant information, particularly at retrieval.

Evidence-based medicine and antiepileptic drugs.

Evidence based health care uses systematic literature reviews with statistical strategies like meta-analysis to aid decision-making. This information can help clinicians by organizing data and providing up-to-date quantitative summaries of efficacy and adverse effects of treatments. Limitations of meta-analysis include problems inherent in combining data from trials of somewhat different design, choice of appropriate dosages, and summarizing complex questions as a single odds ratios. I summarize the results of a meta-analysis of the following antiepileptic treatments for partial seizures in adults: gabapentin, lamotrigine, topiramate, tiagabine, valproate and the vagal nerve stimulator. Each treatment was significantly more efficacious than placebo, and there were nonsignificant trends toward differences among the treatments in efficacy and tolerability. Quantitative analysis of adverse effects is presented. Absent the availability of a comprehensive randomized controlled trial for comparison, a rigorously conducted meta-analysis provides some useful information.