Untreated Epilepsy Research Articles

Altered spontaneous activity in treatment-naive childhood absence epilepsy revealed by Regional Homogeneity

PurposeTo explore the differences in regional spontaneous activities throughout the whole brain by the Regional Homogeneity (ReHo) method in untreated childhood absence epilepsy (CAE), in order to understand the neuro-pathophysiological mechanism of function impairments in CAE. MethodsThe rest-functional MRI was used to measure the ReHo in 16 patients with untreated CAE and 16 age- and sex-matched healthy controls. The correlations between the ReHo at each voxel of the whole brain and duration of epilepsy were analyzed.Results: Compared with healthy controls, we found that ReHo was decreased in bilateral thalamus, caudate, posterior lobe of cerebellum and areas mainly in the default mode network (DMN) (including precuneus and posterior cingulate cortex-PCC, bilateral inferior lateral parietal lobule). The increase of ReHo was found in bilateral insula, left occipital cortex. Moreover, a correlation analysis of the ReHo measurement versus the epilepsy duration was performed, and highly positive correlation was observed in precuneus/PCC and supplementary motor area (SMA). SignificanceThe current findings demonstrated alterations of ReHo in the striato-thalamo-cortical network in drug naïve CAE subjects during interictal resting state. Some regions with decreased ReHo followed the pattern of ‘default’ state of brain function. In addition, positive correlations between the ReHo values in the precuneus/PCC and SMA and the disease duration were identified. These results indicate that the involvement of these regions may be related to the pathomechanisms of seizure generation and the neurological deficits observed in CAE patients. ReHo has demonstrated the capability to characterize spontaneous brain dysfunction in epilepsy.

Sleep disorders in patients with epilepsy

Introduction The close relationship between sleep and epilepsy is widely documented in clinical and electrophysiological investigations. However comorbidity between epilepsy and sleep disorders is poorly investigated in the literature and rarely taken into consideration by clinicians in general practice. We try to assess the prevalence of sleep disorders in patients with drug-resistant partial-seizure epilepsy. Materials and methods Data from a consecutive cohort of patients with refractory partial-seizure epilepsy admitted in the inpatient video-EEG monitoring unit in a tertiary referral hospital over a two-year period were analyzed. Patients with a comorbidity of psychiatric disorders were excluded. Patients were tested for sleep disorders using the Thomas Memorial Hospital Sleep Disorders Centre questionnaire. Data were compared with a control group matched with patients by age and demography. Results 18 patients and 19 controls were included in the study. 19% of patients and 12% of controls complain of symptoms of possible insomnia, 20% of patients and 7% of controls of possible obstructive sleep apnea, 17% of patients and 10% of controls of excessive daytime sleepiness, 32% of patients and 11% of controls of possible restless leg syndrome and/or possible periodic leg movement syndrome, and 43% of patients and 5% of controls of possible parasomnia. Conclusion The results of this study demonstrate that many patients with epilepsy complain of sleep disorder symptoms. A greater awareness among clinicians of the comorbidities between sleep disorders and epilepsy may help to prevent misdiagnosis and mistreatment. Further studies are needed in order to investigate the prevalence and impact of these comorbidities in patients with controlled and untreated epilepsy. Acknowledgements Inpatient video-EEG monitoring Unit, Epilepsy Unit, University Hospital Virgen del Rocio. Seville, Spain.

Epileptic baboons have lower numbers of neurons in specific areas of cortex

Epilepsy is characterized by recurrent seizure activity that can induce pathological reorganization and alter normal function in neocortical networks. In the present study, we determined the numbers of cells and neurons across the complete extent of the cortex for two epileptic baboons with naturally occurring seizures and two baboons without epilepsy. Overall, the two epileptic baboons had a 37% average reduction in the number of cortical neurons compared with the two nonepileptic baboons. The loss of neurons was variable across cortical areas, with the most pronounced loss in the primary motor cortex, especially in lateral primary motor cortex, representing the hand and face. Less-pronounced reductions of neurons were found in other parts of the frontal cortex and in somatosensory cortex, but no reduction was apparent in the primary visual cortex and little in other visual areas. The results provide clear evidence that epilepsy in the baboon is associated with considerable reduction in the numbers of cortical neurons, especially in frontal areas of the cortex related to motor functions. Whether or not the reduction of neurons is a cause or an effect of seizures needs further investigation.

Psychiatric comorbidity and social aspects in pregnant women with epilepsy — The Norwegian Mother and Child Cohort Study

ObjectiveThe objective of this study was to investigate psychiatric disease and social aspects in young women with epilepsy before and during pregnancy. MethodThe study included self-reported data from 106,935 pregnancies. ResultsSeven hundred eleven women reported having epilepsy, and 45.9% of them were using antiepileptic drugs (AEDs). Compared to the reference group, self-reported eating disorders and depression were increased in the untreated epilepsy group before pregnancy. Both AED-treated and untreated women with epilepsy reported higher depression scores as assessed by the Hopkins Symptom Checklist, and the Lifetime Major Depression scale was increased in AED-treated women. Antiepileptic drug treatment was linked to low income (27.4% vs. 18.4%, p<0.001) and no income (5.5% vs. 2.6%, p=0.001). Low educational level was associated with epilepsy in AED-treated and untreated women (50.5%, p<0.001 and 46.9%, p<0.001 vs. 32.2%), as was unemployment due to disability (7.9%, p<0.001 and 6.5%, p<0.001 vs. 1.5%) and single parenting (4.4%, p=0.016 and 4.5%, p=0.007 vs. 2.4%). No difference was found for smoking, alcohol use, or narcotic use. ConclusionSymptoms of depression were associated with epilepsy both during and before pregnancy. Epilepsy was linked to eating disorders before pregnancy. Unemployment, single parenting, and low educational level were linked to epilepsy in young pregnant females. Efforts aiming at treatment and screening for psychiatric comorbidity in pregnant women with epilepsy are important in the follow-up of these patients.

The nature history of untreated epilepsy in rural areas in Tibetan areas

The nature history of untreated epilepsy in rural areas in Tibetan areas

Updated ILAE Review of Antiepileptic Drug Efficacy

The International League Against Epilepsy (ILAE) Subcommission on AED Guidelines reviewed the literature from July 2005 to March 2012 and combined results with previous analysis (2006) to provide a comprehensive update of level of AED efficacy as initial monotherapy with newly diagnosed or untreated epilepsy.

Evaluation of left ventricular diastolic function by tissue Doppler imaging in patients with newly diagnosed and untreated primary generalized epilepsy

PurposeThe effects of epilepsy and seizures on cardiac functions have been documented, and this association has drawn attention in recent years. The aim of this study was to investigate left ventricle (LV) diastolic function by tissue Doppler imaging (TDI) in patients with newly diagnosed and untreated primary generalized epilepsy (PGE). MethodThirty newly diagnosed and untreated PGE patients (14 females, mean age 27.60±9.64 years) and 30 healthy age- and gender-matched control subjects (14 females, mean age 29.47±6.89 years) were included in the study. The LV functions of the study cohort were evaluated using conventional echocardiography and TDI. ResultsThere were no significant differences found between the two groups regarding the left atrium diameter, left atrium volume index, interventricular septum and posterior wall thickness, LV end diastolic diameter, and LV end diastolic volume (p>0.05 for each parameter). PGE patients exhibited a higher LV end systolic diameter and LV end systolic volume compared to the controls (p<0.001 for each parameter). Thus, the fractional shortening and ejection fraction were lower in the PGE patients (p<0.001 for each parameter). The E to average e′ ratio, the most important noninvasive indicator of LV filling pressure, was significantly higher in patients with PGE (8.31±2.78 vs. 6.95±1.26, p=0.018). ConclusionThe present study reports the systolic and diastolic dysfunction of LV in newly diagnosed PGE patients compared to control subjects. Taken together, the screening of epileptic patients using conventional echocardiography and TDI may be useful to evaluate the effects of epilepsy on cardiac functions.

Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes

The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.

MRNA blood expression patterns in new-onset idiopathic pediatric epilepsy.

Determine if blood messenger RNA (mRNA) expression patterns in children with newly diagnosed untreated idiopathic epilepsy are different from those in healthy controls. Determine the differential expression patterns between epilepsy patients with generalized onset or partial onset seizures compared to healthy controls. Whole blood was obtained from otherwise healthy pediatric patients with newly diagnosed untreated idiopathic epilepsy along with healthy pediatric controls. mRNA was isolated and hybridized to Affymetrix HGU 133 2.0+ microarrays. Analysis was performed using Genespring. Differentially expressed gene lists resulted from comparison of (1) epilepsy and control groups and (2) seizure type subgroups with controls. Tissue expression and gene ontology analysis was performed using DAVID. Thirty-seven epilepsy patients and 28 controls were included. Overall, 575 genes were differentially expressed in subjects with epilepsy compared to controls. The generalized seizure subgroup versus control (GvC) gene list and the partial seizure subgroup versus control (PvC) gene list were different (p < 0.05). Tissue expression analysis identified almost half of the genes in GvC and PvC as brain based. Functional group analysis identified several biologically relevant pathways. In GvC, these included mitochondria and lymphocyte activation. In PvC, we identified apoptosis, inflammatory defense, and cell motion pathways. A unique, biologically meaningful mRNA expression pattern is detectable in whole blood of pediatric subjects with new-onset and untreated epilepsy. This analysis finds many similar pathways to those identified in brain studies examining lesional intractable epilepsy. Blood mRNA expression patterns show promise as a target for biomarker development in pediatric epilepsy.

Critical determinants of the epilepsy treatment gap: A cross‐national analysis in resource‐limited settings

Epilepsy is one of the most common serious neurologic disorders worldwide. Our objective was to determine which economic, health care, neurology, and epilepsy-specific resources were associated with untreated epilepsy in resource-constrained settings. A systematic review of the literature identified community-based studies in resource-constrained settings that calculated the epilepsy treatment gap, the proportion with untreated epilepsy, from prevalent active epilepsy cases. Economic, health care, neurology, and epilepsy-specific resources were taken from existing datasets. Poisson regression models with jackknifed standard errors were used to create bivariate and multivariate models comparing the association between treatment status and economic and health resource indicators. Relative risks were reported. Forty-seven studies of 8,285 individuals from 24 countries met inclusion criteria. Bivariate analysis demonstrated that individuals residing in rural locations had significantly higher risks of untreated epilepsy (relative risk [RR] 1.63; 95% confidence interval [CI] 1.26-2.11). Significantly lower risks of untreated epilepsy were observed for higher physician density (RR 0.65, 95% CI 0.55-0.78), presence of a lay (RR 0.74, 95% CI 0.60-0.91) or professional association for epilepsy (RR 0.73, 95% CI 0.59-0.91), or postgraduate neurology training program (RR 0.67, 95% CI 0.55-0.82). In multivariate models, higher physician density maintained significant effects (RR 0.67; 95% CI 0.52-0.88). Even among resource-limited regions, people with epilepsy in countries with fewer economic, health care, neurology, and epilepsy-specific resources are more likely to have untreated epilepsy. Community-based epilepsy care programs have improved access to treatment, but in order to decrease the epilepsy-treatment gap, poverty and inequalities of health care, neurology, and epilepsy resources must be dealt with at the local, national, and global levels.

PS25 Discontinuation of Antiepileptic Drugs in Pregnancy: A UK Population Based Study in the Health Improvement Network (THIN)

BackgroundSince the thalidomide tragedy in the 1960s, many women are concerned with the use of drugs in pregnancy. Antiepileptic drugs (AEDs) are commonly used to treat epilepsy and bipolar disorders...

Subdural Pharmacotherapy for the Treatment of Intractable Focal Neocortical Epilepsy

The Subdural Pharmacotherapy Device (SPD) is an experimental medical implant for the treatment of intractable focal neocortical epilepsy. The device performs spatially and temporally controlled administration of seizurepreventing drugs into the subarachnoid space overlaying the neocortical seizure focus or foci. This is accomplished with the use of a multifunction subdural strip, through which the device periodically (a) delivers drugs to achieve local treatment without systemic side-effects, (b) receives electrophysiological feedback on this local treatment so that neither ineffective nor toxic drug administration can take place, and (c) removes local cerebrospinal fluid (CSF) containing tissue reaction cells and proteins to maintain adequate transmeningeal drug diffusion into the seizure focus for long periods. The present drug-of-choice that emerged for this device is muscimol, a potent GABAA receptor agonist. Experimental data obtained in freely-behaving nonhuman primates implanted with the muscimol-delivering SPD showed that this treatment can fully prevent focal neocortical seizures for many months without tolerance. Neurological symptoms or behavioral abnormalities did not develop during SPD-use, for at least a year. Based on all accumulated data, the muscimol-delivering SPD seems to have clinical potential. The present device needs to be adapted to human use, and its safety and antiepileptic efficacy need to be confirmed in further studies. Should this effort succeed, it may well lead to a new therapeutic option for at least a subgroup of the approximately 150,000 US patients who suffer from otherwise untreatable focal neocortical epilepsy. Keywords: Epilepsy, subdural pharmacotherapy, subarachnoid space, neocortex, muscimol, drug delivery device, nonhuman primate, acetylcholine, focal neocortical seizures

Subdural Pharmacotherapy for the Treatment of Intractable Focal Neocortical Epilepsy

The Subdural Pharmacotherapy Device (SPD) is an experimental medical implant for the treatment of intractable focal neocortical epilepsy. The device performs spatially and temporally controlled administration of seizurepreventing drugs into the subarachnoid space overlaying the neocortical seizure focus or foci. This is accomplished with the use of a multifunction subdural strip, through which the device periodically (a) delivers drugs to achieve local treatment without systemic side-effects, (b) receives electrophysiological feedback on this local treatment so that neither ineffective nor toxic drug administration can take place, and (c) removes local cerebrospinal fluid (CSF) containing tissue reaction cells and proteins to maintain adequate transmeningeal drug diffusion into the seizure focus for long periods. The present drug-of-choice that emerged for this device is muscimol, a potent GABAA receptor agonist. Experimental data obtained in freely-behaving nonhuman primates implanted with the muscimol-delivering SPD showed that this treatment can fully prevent focal neocortical seizures for many months without tolerance. Neurological symptoms or behavioral abnormalities did not develop during SPD-use, for at least a year. Based on all accumulated data, the muscimol-delivering SPD seems to have clinical potential. The present device needs to be adapted to human use, and its safety and antiepileptic efficacy need to be confirmed in further studies. Should this effort succeed, it may well lead to a new therapeutic option for at least a subgroup of the approximately 150,000 US patients who suffer from otherwise untreatable focal neocortical epilepsy. Keywords: Epilepsy, subdural pharmacotherapy, subarachnoid space, neocortex, muscimol, drug delivery device, nonhuman primate, acetylcholine, focal neocortical seizures

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

To investigate the intrinsic brain connections at the time of interictal generalized spike-wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). The EEG-functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug-naïve CAE, and three different brain networks-the default mode network (DMN), cognitive control network (CCN), and affective network (AN)-were investigated. Cross-correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus-dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC-inferior frontal junction (IFJ), and pre-supplementary motor area (pre-SMA) subregions connectivity disruption in CCN; ACC-ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. The current findings demonstrate significant alterations of resting-state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro-pathophysiological mechanism of psychosocial function impairments in patients with CAE.

A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy

To conduct a meta-analysis to quantify whether valproate (VPA) is associated with an increased risk of polycystic ovary syndrome (PCOS) in women with epilepsy. A comprehensive literature search for all published studies of MEDLINE and EMBASE was performed for English language studies published from 1st January 1990 to 4th February 2011. The studies included should be prospective and controlled. We then performed a meta-analysis to identify polycystic ovary syndrome in women with epilepsy treated with VPA. The meta-analysis included 11 studies that met inclusion/exclusion criteria, involving 556 women with epilepsy treated with VPA, 593 women treated with other antiepileptic drugs (AEDs), 120 women with untreated epilepsy and 329 healthy controls. The calculated incidence of PCOS in women treated with VPA was higher than that in women treated without VPA (10 studies included, P<0.05, OR 3.04, 95% CI 2.09-4.43). According to different definitions or diagnostic criteria of PCOS, the results were different. VPA's treatment was associated with higher incidence of PCOS in the criteria of hyperandrogenism and/or hyperandrogenemia, oligoovulation (4 studies included, P<0.05, OR 3.22, 95% CI 1.79-5.80), and in the criteria of two of the three following fulfilled: appearance of polycystic ovary (PCO) on the ultrasonogram, elevated serum testosterone levels and irregular (oligo-/amenorrhea) menstrual cycles (1 post hoc reanalysis study included, P<0.05, OR 5.01, 95% CI 2.40-10.49. Another prospective and crosssectional included, P<0.05, OR 3.50, 95% CI 1.30-9.40). However, in the criteria of PCO with ovulatory dysfunction (polymenorrhea, amenorrhea, or oligomenorrhea), clinical and/or biochemical evidence of hyperandrogenism according to National Institutes of Child Health and Human Development (NICHHD) and The National Institutes of Health (NIH) Consensus Conference, VPA did not increase the PCOS incidence compared with other AEDs (4 studies included, P>0.05, OR 1.37, 95% CI 0.59-3.19). Data on PCOS's components were pooled. PCO was higher in women treated with VPA than in those without VPA (6 studies included, P<0.05, OR 1.94, 95% CI 1.28-2.95) or in healthy controls (4 studies included, P<0.05, OR 4.99, 95% CI 2.97-8.37). VPA treated women were more subject to hyperandrogenism than non-VPA treated women (5 studies included, P<0.05, OR 2.35, 95% CI 1.57-3.53). There is significant difference of menstrual disorders between VPA treated women and non-VPA treated women (7 studies included, P<0.05, OR 1.64, 95% CI 1.19-2.25). Results of this meta-analysis suggest that the raw incidence of PCOS in VPA treated women with epilepsy is approximately 1.95 folds that in other AEDs treated women. PCOS and its components may be associated with VPA treated women with epilepsy. We recommend monitoring PCOS and its components in women with VPA mono-/polytherapy. In light of limitations and heterogenicity, there is surely the need for more prospective studies to identify VPA and PCOS.

AED discontinuation may not be dangerous in seizure-free patients

The decision to continue or to stop anticonvulsant treatment in patients with prolonged seizure remission is still a matter of debate. There is no evidence that continued treatment guarantees permanent seizure freedom. Up to 50% of patients achieve terminal remission (i.e., off drugs). Almost one-half of patients with untreated epilepsy are seizure-free for more than 5 years and the number of those with continuing seizures tends to decrease over time. In contrast, a substantial fraction of patients on chronic treatment with antiepileptic drugs (AEDs) may be exposed to clinically relevant adverse effects. Other disadvantages of continuing treatment indefinitely include the teratogenic risk, drug interactions, and the concern that AEDs may be unnecessary. The probability of remaining seizure-free after treatment discontinuation is about 70% at 2 years. Although different combinations of factors are thought to affect the risk of relapse, the prediction of individual outcome before withdrawal remains uncertain. As a consequence, the decision to withdraw or withhold treatment must be still individualized. In any patient, the decision to discontinue treatment should also take into account social aspects like driving license, job and leisure activities as well as emotional and personal factors and adverse effects or drug interactions. Patients will ultimately have to decide themselves whether they wish to discontinue drug treatment.

Cognitive and behavioral effects of lamotrigine and carbamazepine monotherapy in patients with newly diagnosed or untreated partial epilepsy

Purpose In this prospective study, we compared the long-term cognitive and behavioral effects of lamotrigine (LTG) and carbamazepine (CBZ) in patients with newly diagnosed or untreated partial epilepsy. Methods This was a multicenter, open-label, randomized study that compared monotherapy with LTG and CBZ in newly diagnosed or untreated patients with partial epilepsy. We employed an 8-week titration period and a 40-week maintenance period. Neuropsychological tests, Symptom Check List-90, and QOLIE-31 were assessed at baseline, 16 weeks, and 48 weeks after drug treatment. A group-by-time interaction was the primary outcome measure and was analyzed by use of the linear mixed model. Results A total of 110 patients were eligible and 73 completed the 48-week study (LTG, n = 39; CBZ, n = 34). Among the cognitive tests, significant group-by-time interaction was identified only in phonemic fluency of Controlled Oral Word Association Task ( p = 0.0032) and Stroop Color–Word Interference ( p = 0.0283), with a significant better performance for LTG group. All other neuropsychological tests included did not show significant group-by-time interactions. Among the subscales of Symptom Check List-90, significant group-by-time interactions were identified in Obsessive-Compulsive ( p = 0.0005), Paranoid Ideation ( p = 0.0454), Global Severity Index ( p = 0.0194), and Positive Symptom Total ( p = 0.0197), with a significant improvement for CBZ group. QOLIE-31 did not show significant group-by-time interactions. Conclusion Our data suggest that epilepsy patients on LTG have better performance on phonemic fluency and the task of Stroop Color–Word Interference than do patients on CBZ, whereas patients on CBZ had more favorable behavioral effects on two subscales and two global scores of Symptom Check List-90 than did patients on LTG.

Long-Term Developmental Outcome of Children of Women with Epilepsy, Unexposed or Exposed Prenatally to Antiepileptic Drugs

Results of studies investigating the long-term effects of intra-uterine exposure to antiepileptic drugs (AEDs) on cognitive functioning are limited and conflicting. To estimate intellectual development of children prenatally exposed or unexposed to AEDs by assessing IQ scores in a systematic review and meta-analysis. A literature search using Pubmed, EMBASE and Google Scholar from inception to 30 April 2009 was performed to identify all original cohort studies that investigated cognitive functioning after in utero exposure to AEDs. Studies had to include at least one group exposed to an AED and one unexposed group. Data from drug exposed and unexposed controls were combined using a random effects model. Eleven studies met the inclusion criteria. Eight studies (three for valproic acid and five for carbamazepine) evaluated IQ as a measure of cognitive development. IQ was assessed by the Wechsler, Bayley or McCarthy intelligence scales, depending on age. One study investigated phenytoin and one study investigated phenobarbital (phenobarbitone). Because one study was reported in two different publications, seven studies were included in the meta-analysis. In total, the seven selected studies included 67 children exposed in utero to valproic acid and 151 exposed to carbamazepine, and 494 unexposed controls born to healthy women or to women with untreated epilepsy. The mean full-scale IQ (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ) scores in children exposed to valproic acid in utero were 83.9 (95% CI 64.2, 103.6), 93.7 (95% CI 72.6, 114.7) and 88.3 (95% CI 69.9, 106.9), respectively. The mean FSIQ, VIQ and PIQ scores in the control group were 102 (95% CI 90, 116), 101 (95% CI 87, 114) and 99 (95% CI 90, 117), respectively. The mean FSIQ, VIQ and PIQ were all significantly lower in the valproic acid group compared with the unexposed group. The FSIQ and VIQ of children exposed to carbamazepine were not statistically different from those of the unexposed control group. In a sub-analysis of carbamazepine exposure in three studies using the Wechsler intelligence scale, PIQ was significantly lower in children exposed to carbamazepine than in unexposed children. Although our analysis revealed no evidence that untreated maternal epilepsy was associated with a lower IQ in the child, there may have been confounding factors, such as milder epilepsy, in this group. Exposure to valproic acid in pregnancy is associated with significantly reduced intelligence in children whose mothers were treated for epilepsy. Exposure to carbamazepine in pregnancy does not appear to be associated with reduced FSIQ and VIQ in children, although PIQ was lower in the sub-analysis. Clinicians should inform families of the potential cognitive adverse effects of valproic acid. More studies are needed to corroborate these findings.

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

To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission. 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. 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. 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.

Patients with epilepsy: Cognitively compromised before the start of antiepileptic drug treatment?

To compare the cognitive profile of newly diagnosed untreated epilepsy patients with healthy volunteers using a comprehensive neuropsychological test battery. A total of 155 untreated patients with newly diagnosed epilepsy, and no known brain pathology, were assessed before the start of treatment with antiepileptic medication. Their scores across the neuropsychological measures were compared with 87 healthy volunteers from the general population equated for age and sex. After adjusting for age, sex, and education, patients with epilepsy performed significantly worse than healthy volunteers on 6 of 14 cognitive measures, particularly in the domains of memory and psychomotor speed. Cognitive performance was not related to the number of seizures, type of epilepsy, or mood. When an impairment index was calculated, 53.5% patients had a least one abnormal score [>2 standard deviations (SD) below the control mean] on the test battery compared with 20.7% of healthy volunteers. Newly diagnosed untreated patients with epilepsy are cognitively compromised before the start of antiepileptic drug medication. The domains most affected are memory and psychomotor speed. More than one-half of the patients had at least one abnormal test score across the test battery. There were no differences in epilepsy-related or mood variables between those who demonstrated dysfunction and those that did not.