Publications by authors named "Gus A Baker"

104 Publications

European Clinical Neuropsychology: Role in Healthcare and Access to Neuropsychological Services.

Healthcare (Basel) 2021 Jun 15;9(6). Epub 2021 Jun 15.

Department of Psychology, University of Oslo, 0315 Oslo, Norway.

This study analyzed aspects of the work of clinical neuropsychologists across Europe. There are no published comparisons between European countries regarding the nature of clinical neuropsychologists' work. Forty-one national psychological and neuropsychological societies were approached, of which 31 (76%) responded. Data from seven countries with less than 10 neuropsychologists were excluded. A license is required to practice clinical neuropsychology in 50% of the countries. Clinical neuropsychologists work independently in 62.5%. Diagnostic/assessment work is the most frequently reported activity (54%). Most neuropsychologists work in public hospitals, followed by health centers. Adult neuropsychology was the most frequent area of activity. Services in public institutions are covered by public entities (45.8%), or by a combination of patient funds and public entities (29.2%) and only 4.2% by the patient; whereas services in private institutions are covered by the patient (26.1%) and the combination of patient, public entities (21.7%) or patient and private entities (17.4%). The data suggest that the number of neuropsychologists working across European countries is considerably low in comparison to other medical professionals. The results of the survey identified similar aspects of neuropsychologists' work, despite variations in terms of reimbursement and mechanisms, reflecting economic and healthcare differences. Estimates on the number of clinical neuropsychologists suggest insufficient access to neuropsychological services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/healthcare9060734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232602PMC
June 2021

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

Lancet 2021 04;397(10282):1375-1386

The Alan Richens Epilepsy Unit, University Hospital of Wales, Cardiff, Wales, UK.

Background: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy.

Methods: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64).

Findings: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years.

Interpretation: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate.

Funding: National Institute for Health Research Health Technology Assessment Programme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00246-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047813PMC
April 2021

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

Lancet 2021 Apr;397(10282):1363-1374

The Alan Richens Epilepsy Unit, University Hospital of Wales, Cardiff, Wales, UK.

Background: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy.

Methods: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64).

Findings: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs.

Interpretation: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials.

Funding: National Institute for Health Research Health Technology Assessment programme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00247-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047799PMC
April 2021

Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults.

Epileptic Disord 2019 Jun;21(3):221-234

Department of Psychology, University of Toronto Mississauga and Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, Canada.

In our first paper in this series (Epilepsia 2015; 56(5): 674-681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence-based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long-term assessment of these changes following surgery should form an integral part of the postoperative follow-up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2019.1065DOI Listing
June 2019

Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study.

Epilepsy Behav 2019 03 17;92:154-164. Epub 2019 Jan 17.

Neurology, Emory University, Atlanta, GA, United States of America.

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2018.12.031DOI Listing
March 2019

Intellectual functioning in clinically confirmed fetal valproate syndrome.

Neurotoxicol Teratol 2019 Jan - Feb;71:16-21. Epub 2018 Nov 16.

School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK; Clinical Sciences, Murdoch Children's Research Institute, Flemington Road, Parkville, Victoria 3052, Australia.

Background: An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS).

Methods: This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed.

Results: The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6-27 years) was 19 points lower (19.55, 95% CI -24.94 to 14.15), and IQ scores <70 were present in 26%. The mean differences for verbal comprehension (21.07, 95% CI -25.84 to -16.29), working memory (19.77, 95% CI -25.00 to -14.55) and processing speed (16.87, 95% CI -22.24 to -11.50) performances were poorer than expected with the mean differences over one standard deviation from the comparison group. Sixty one percent of cases demonstrated disproportionately lower verbal comprehension ability. There were no significant group differences for IQ in high vs. moderate dose valproate or mono vs. polytherapy. There were no differences in IQ between those with and those without a major congenital malformation. The requirement for educational intervention was high at 74%.

Conclusion: Intellectual difficulties are a central feature of FVS and are more severe in their presentation in individuals with a diagnosis of valproate embryopathy. Individuals with FVS who present with the characteristic facial presentation should be considered at high risk of cognitive difficulties regardless of the dose of valproate exposure or the presence of a major congenital malformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ntt.2018.11.003DOI Listing
May 2020

Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs.

Clin Pharmacol Ther 2019 03 25;105(3):672-683. Epub 2018 Oct 25.

Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK.

Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients' benefit-risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients' preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpt.1231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491963PMC
March 2019

Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate.

Neurology 2016 Nov 31;87(18):1943-1953. Epub 2016 Aug 31.

From the Institute of Human Development (R.L.B. J.C.-S.), Department of Clinical Psychology (P.T.), and Centre for Women's Mental Health (R.S.), University of Manchester; Royal Manchester Children's Hospital (R.L.B.), Manchester; Department of Clinical Psychology (R.C.), University of Lancaster; Departments of Biostatistics (C.P.C., M.G.-F.) and Molecular and Clinical Pharmacology (G.A.B.), University of Liverpool; Neuropsychology Trauma Pathway (C.R.), Merseycare NHS Trust, Liverpool; Manchester Centre for Genomic Medicine (J.C.-S.), St Mary's Hospital, Manchester; and Department of Neurology (B.I., J.I.M.), Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.

Objective: To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning.

Methods: This was a cross-sectional observational study. Children exposed to monotherapy levetiracetam (n = 42), topiramate (n = 27), or valproate (n = 47) and a group of children born to women who had untreated epilepsy (n = 55) were enrolled retrospectively from the UK Epilepsy and Pregnancy Register. Assessor-blinded neuropsychological assessments were conducted between 5 and 9 years of age. Information was collected on demographic and health variables and adjusted for in multiple regression analyses.

Results: In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in child cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing dose of valproate, however, was associated with poorer full-scale IQ (-10.6, 95% confidence interval [CI] -16.3 to -5.0, p < 0.001), verbal abilities (-11.2, 95% CI -16.8 to -5.5, p < 0.001), nonverbal abilities (-11.1, 95% CI -17.3 to -4.9, p < 0.001), and expressive language ability (-2.3, 95% CI -3.4 to -1.6, p < 0.001). Comparisons across medications revealed poorer performance for children exposed to higher doses of valproate in comparison to children exposed to higher doses of levetiracetam or topiramate.

Conclusions: Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000003157DOI Listing
November 2016

Fetal antiepileptic drug exposure and cognitive outcomes.

Seizure 2017 Jan 14;44:225-231. Epub 2016 Oct 14.

Department of Molecular and Clinical Pharmacology, University of Liverpool, UK.

Purpose: Data highlighting valproate as a human teratogen put in context the need to balance both maternal and fetal needs; maximising maternal health whilst minimising fetal risk. This led to increased research efforts to understand the associated risks with AED treatments.

Methods: A review of currently published literature was undertaken.

Results: In utero exposure to valproate was associated with a range of poorer neurodevelopmental outcomes when compared to control children and children exposed to other antiepileptic drugs (AEDs). Children exposed to carbamazepine were not found by the majority of studies to have poorer early development, although there is a lack of evidence regarding specific cognitive skills later in childhood and adolescence. Research regarding lamotrigine was limited to a small number of studies but suggests early global development or school aged IQ does not differ from control children, but less is known about specific cognitive skills. Evidence for the other AEDs including levetiracetam and topiramate were significantly limited.

Conclusions: Despite an improvement in momentum the evidence remains incomplete for neurodevelopmental outcomes and this limits evidence-based decision making. Further efforts are required to enhance the treatment of women by giving them the confidence that both the risks and the benefits of commonly used AEDs are known. Future research should also seek to increase our understanding of the children who experience neurodevelopmental difficulties in the context of exposure in the womb to AEDs and what interventions may be successful in maximising the outcome of these children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2016.10.006DOI Listing
January 2017

WITHDRAWN: Psychological treatments for epilepsy.

Cochrane Database Syst Rev 2016 Feb 25;2:CD002029. Epub 2016 Feb 25.

Department of Neurology, SIMS Hospitals, 100 feet Road, Vadapalani, Chennai, Tamil Nadu, India, 600026.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD002029.pub4DOI Listing
February 2016

Does the concept of resilience contribute to understanding good quality of life in the context of epilepsy?

Epilepsy Behav 2016 Mar 17;56:153-64. Epub 2016 Feb 17.

Department of Public Health & Policy, University of Liverpool, Liverpool, UK.

A significant body of research highlights negative impacts of epilepsy for individual quality of life (QOL). Poor seizure control is frequently associated with reporting of poor QOL and good seizure control with good QOL; however, this is not a universal finding. Evidence suggests that some people enjoy good QOL despite ongoing seizures while others report poor QOL despite good seizure control. Understanding the factors that influence QOL for people with epilepsy and the processes via which such factors exert their influence is central to the development of interventions to support people with epilepsy to experience the best possible QOL. We present findings of a qualitative investigation exploring influences and processes on QOL for people with epilepsy. We describe the clinical, psychological, and social factors contributing to QOL. In particular, we focus on the value of the concept of resilience for understanding quality of life in epilepsy. Based on our analysis, we propose a model of resilience wherein four key component sets of factors interact to determine QOL. This model reflects the fluid nature of resilience that, we suggest, is subject to change based on shifts within the individual components and the interactions between them. The model offers a representation of the complex influences that act and interact to either mitigate or further compound the negative impacts of epilepsy on individual QOL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2016.01.002DOI Listing
March 2016

NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy.

Epilepsy Behav 2016 Jan 17;54:117-27. Epub 2015 Dec 17.

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK. Electronic address:

Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy. A total of 82 patients who had previously undergone detailed neuropsychological assessment were genotyped for single nucleotide polymorphisms (SNPs) across the NRSF and BDNF genes. Putatively functional SNPs were included in a genetic association analysis with specific cognitive domains, including memory, psychomotor speed, and information processing. Cross-sectional and longitudinal designs were used to explore genetic influences on baseline cognition at diagnosis and change from baseline over the first year since diagnosis, respectively. We found a statistically significant association between genotypic variation and memory function at both baseline (NRSF: rs1105434, rs2227902 and BDNF: rs1491850, rs2030324, rs11030094) and in our longitudinal analysis (NRSF: rs2227902 and BDNF: rs12273363). Psychomotor speed was also associated with genotype (NRSF rs3796529) in the longitudinal assessment. In line with our previous work on general cognitive function in the healthy aging population, we observed an additive interaction between risk alleles for the NRSF rs2227902 (G) and BDNF rs6265 (A) polymorphisms which was again consistent with a significantly greater decline in delayed recall over the first year since diagnosis. These findings support a role for the NRSF-BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2015.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732989PMC
January 2016

Neuropsychological and psychological interventions for people with newly diagnosed epilepsy.

Cochrane Database Syst Rev 2015 Jul 22(7):CD011311. Epub 2015 Jul 22.

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Clinical Sciences Centre for Research and Education, Lower Lane, Fazakerley, Liverpool, UK, L9 7LJ.

Background: Many people with epilepsy report experiencing psychological difficulties such as anxiety, depression and neuropsychological deficits including memory problems. Research has shown that these difficulties are often present not only for people with chronic epilepsy but also for people with newly diagnosed epilepsy. Despite this, there are very few published interventions that detail means to help people with newly diagnosed epilepsy manage these problems.

Objectives: To identify and assess possible psychological and neuropsychological interventions for adults with newly diagnosed epilepsy.

Search Methods: We searched the following databases on 30 June 2015: the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), SCOPUS, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).

Selection Criteria: This review includes all randomised controlled trials, quasi-randomised controlled trials, prospective cohort controlled studies, and prospective before and after studies which include psychological or neuropsychological interventions for people with newly diagnosed epilepsy. We excluded studies that included people with epilepsy and any other psychological disorder or neurological condition. We excluded studies carried out which recruited only children.

Data Collection And Analysis: We used the standard methodological procedure expected by The Cochrane Collaboration. Two authors independently completed data extraction and risk of bias analysis. The results of this were cross-checked and third author resolved any discrepancies. In the event of missing data, we contacted the study authors. Meta-analysis was not completed due to differences in the intervention and outcomes reported in the two studies.

Main Results: We included two randomised controlled trials assessing psychological interventions for people with newly diagnosed epilepsy. One study assessed a cognitive behavioural intervention (CBI) in an adolescent population. This study was rated as low quality. One study assessed a specialist nurse intervention in an adult population. This study was rating as very low quality.We rated one study as having unclear risk of bias and one study as having high risk of bias.The CBI study indicated that this intervention could significantly reduce depressive symptoms in people with subthreshold depressive disorder. However, the study assessing the effectiveness of a nurse intervention found no significant benefit for depressive symptoms,but did find that in individuals with the least knowledge of epilepsy, a nurse intervention could increase their knowledge of epilepsy scores.

Authors' Conclusions: Meta-analysis was not possible as we identified only two studies and they utilised different interventions and outcome measures.Previous research has highlighted the impact of psychological and neuropsychological difficulties experienced by people with epilepsy and the negative effect this has on their quality of life. The main finding of this review is that there is a paucity of research assessing possible neuropsychological and psychological interventions for adults with newly diagnosed epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD011311.pub2DOI Listing
July 2015

Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

Br J Clin Pharmacol 2015 Nov 22;80(5):1149-59. Epub 2015 Aug 22.

Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor.

Aim: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services.

Methods: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect.

Results: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV.

Conclusion: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631187PMC
November 2015

Indications and expectations for neuropsychological assessment in routine epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013-2017.

Epilepsia 2015 May 16;56(5):674-81. Epub 2015 Mar 16.

Department of Psychology, University of Toronto Mississauga, Toronto, Canada.

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12962DOI Listing
May 2015

Quality-of-life outcomes of initiating treatment with standard and newer antiepileptic drugs in adults with new-onset epilepsy: findings from the SANAD trial.

Epilepsia 2015 Mar 29;56(3):460-72. Epub 2015 Jan 29.

Department of Public Health &Policy, University of Liverpool, Liverpool, United Kingdom.

Objective: To compare quality-of-life (QoL) outcomes over 2 years following initiation of treatment with a standard or newer antiepileptic drug (AED) in adults with new-onset epilepsy. To examine the impact of seizure remission and failure of initial treatment on QoL outcomes measured over 2 years.

Methods: We conducted a pragmatic, randomized, unblinded, multicenter, parallel-group clinical trial (the Standard and New Antiepileptic Drugs [SANAD] trial) comparing clinical and cost effectiveness of initiating treatment with carbamazepine versus lamotrigine, gabapentin, oxcarbazepine and topiramate, and valproate versus lamotrigine and topiramate. QoL data were collected by mail at baseline, 3 months, and at 1 and 2 years using validated measures. These data were analyzed using longitudinal data models. Continuous QoL measures, time to 12-month remission and time to treatment withdrawal were explored using joint models.

Results: Baseline questionnaires were returned by 1,575 adults; 1,439 returned the 3-month questionnaire, 1,274 returned the 1-year questionnaire, and 1,121 returned the 2-year questionnaire. There were few statistically significant differences between drugs over 2 years in QoL outcomes. Significant association was identified between QoL scores over the 2-year time frame and the risk of experiencing a 12-month remission or treatment withdrawal over that period.

Significance: The choice of initial treatment had no significant effect on QoL by 2-year follow-up. However, overall QoL was reduced with continued seizures, adverse events, and failure of the initial treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12913DOI Listing
March 2015

Self-reported anxiety and sleep problems in people with epilepsy and their association with quality of life.

Epilepsy Behav 2015 Feb 16;43:149-58. Epub 2015 Jan 16.

Department of Molecular and Clinical Pharmacology, University of Liverpool, UK.

Comorbidities are common in epilepsy, and their role in quality of life (QOL) is receiving increasing scrutiny. Considerable attention has been focused on the role of depression, the most common comorbidity, with rather less attention paid to its frequent concomitant, anxiety, and other conditions known to be at increased prevalence among people with epilepsy (PWE) when compared to the general population. In this paper, we report findings from a UK-based survey in which we examined self-reporting of two common comorbidities, anxiety and sleep problems, factors associated with them, and their role in QOL in people with and without epilepsy. Data were obtained via mailed questionnaires, supplemented by an internet survey, from PWE and age- and gender-matched controls. Based on self-reported symptoms, PWE were at higher risk of anxiety and sleep problems. Contributory factors for anxiety included poorer general health, worry about seizures, and self-reported antiepileptic drug (AED) side effects. Good social support emerged as protective for anxiety in PWE. Nighttime sleep problems were very common even in controls but were further elevated in PWE. Antiepileptic drug adverse events emerged as an important contributory factor for sleep problems. Trait anxiety emerged as significant for defining overall QOL, and its importance over state anxiety supports the notion of anxiety in PWE as a primarily premorbid condition. In contrast, sleep quality was not consistently predictive of QOL. Our study has important implications for clinical management, emphasizing the need for a holistic approach to address wider patient-reported problems as well as any epilepsy-specific ones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2014.09.071DOI Listing
February 2015

IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study.

Neurology 2015 Jan 24;84(4):382-90. Epub 2014 Dec 24.

From the Departments of Molecular and Clinical Pharmacology (G.A.B.), Biostatistics (C.P.C., M.G.-F.), and Clinical Psychology (R.S.), Institute of Infection and Global Health (M.J.C., A.G.), and Alder Hey Children's Hospital & Institute of Infection & Global Health (R.K.), University of Liverpool; Institute of Human Development (R.L.B., J.C.-S.), University of Manchester; Manchester Academic Health Sciences Centre (R.L.B., M.B., G.M., J.C.-S.), Central Manchester University Hospitals Foundation Trust, UK; Department of Neurology (M.J.C.), Georgia Regents University, Augusta; Department of Neurology & Pediatrics (D.W.L.), Emory University, Atlanta, GA; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA.

Objective: To delineate the risk to child IQ associated with frequently prescribed antiepileptic drugs.

Methods: Children born to women with epilepsy (n = 243) and women without epilepsy (n = 287) were recruited during pregnancy and followed prospectively. Of these, 408 were blindly assessed at 6 years of age. Maternal and child demographics were collected and entered into statistical models.

Results: The adjusted mean IQ was 9.7 points lower (95% confidence interval [CI] -4.9 to -14.6; p < 0.001) for children exposed to high-dose (>800 mg daily) valproate, with a similar significant effect observed for the verbal, nonverbal, and spatial subscales. Children exposed to high-dose valproate had an 8-fold increased need of educational intervention relative to control children (adjusted relative risk, 95% CI 8.0, 2.5-19.7; p < 0.001). Valproate at doses <800 mg daily was not associated with reduced IQ, but was associated with impaired verbal abilities (-5.6, 95% CI -11.1 to -0.1; p = 0.04) and a 6-fold increase in educational intervention (95% CI 1.4-18.0; p = 0.01). In utero exposure to carbamazepine or lamotrigine did not have a significant effect on IQ, but carbamazepine was associated with reduced verbal abilities (-4.2, 95% CI -0.6 to -7.8; p = 0.02) and increased frequency of IQ <85.

Conclusions: Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000001182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336006PMC
January 2015

Comments on De Boer JE et al. The global burden and stigma of epilepsy. Epilepsy & behavior 2008;12:540-546.

Authors:
Gus A Baker

Epilepsy Behav 2014 Nov 25;40:20-1. Epub 2014 Oct 25.

Neurological Sciences, University of Liverpool, Clinical Sciences Building, Fazakerley, Liverpool L9 7LJ, UK. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2014.08.123DOI Listing
November 2014

A comprehensive neuropsychological description of cognition in drug-refractory juvenile myoclonic epilepsy.

Epilepsy Behav 2014 Jul 2;36:124-9. Epub 2014 Jun 2.

Wales Epilepsy Research Network (WERN), College of Medicine, Swansea University, Swansea SA2 8PP, UK. Electronic address:

The study of juvenile myoclonic epilepsy is important in that: it is common and heterogeneous; the etiology is unknown; and patients report broad cognitive problems. We utilized a broad battery of neuropsychometric tests to assess the following: intellectual function, memory, language and naming, executive function, the impact of epilepsy, and antiepilepsy drug side effects. Sixty people with drug-refractory JME were interviewed, and performance was profoundly impaired across the range of tests. Impairments included the following: full-scale IQ (89, p<0.001); processing speed (86, p<0.001); visual memory (immediate and delayed) more affected than verbal memory; verbal fluency and inhibition (p<0.001); and self-reported drug side effects (p<0.001). Eighty-three percent of patients exhibited frank executive dysfunction, which was moderate to severe in 66%. Regression modeling confirmed that an early age at onset and the need for polytherapy were associated with poorer cognitive outcomes. This study confirms previous reports of executive dysfunction in a larger cohort and with greater statistical rigor. We also identified a high prevalence of neurotoxicity symptoms such as fatigue and poorer functioning across intellectual and memory tests than had previously been reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2014.04.027DOI Listing
July 2014

Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years.

JAMA Pediatr 2014 Aug;168(8):729-36

Departments of Neurology and Pediatrics, Emory University, Atlanta, Georgia.

Importance: Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities.

Objectives: To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years.

Design, Setting, And Participants: Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery.

Main Outcomes And Measures: Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures.

Results: In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95% CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95% CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95% CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95% CI, 0-7] points higher for breastfed children, P = .03).

Conclusions And Relevance: No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs.

Trial Registration: clinicaltrials.gov Identifier: NCT00021866.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2014.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122685PMC
August 2014

Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

Epilepsy Behav 2014 Jun 13;35:72-7. Epub 2014 May 13.

Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, UK.

Purpose: The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related.

Method: Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured.

Results: Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores.

Conclusion: This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2014.03.026DOI Listing
June 2014

WITHDRAWN: Preconception counselling for women with epilepsy to reduce adverse pregnancy outcome.

Cochrane Database Syst Rev 2014 Mar 19(3):CD006645. Epub 2014 Mar 19.

The Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool, UK, L9 7LJ.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD006645.pub3DOI Listing
March 2014

Exploring loss and replacement of loss for understanding the impacts of epilepsy onset: a qualitative investigation.

Epilepsy Behav 2014 Apr 13;33:59-68. Epub 2014 Mar 13.

Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Previous research identifies loss as a key concept for our understanding of the impact of chronic illness. In this in-depth qualitative study, we explored the utility of the concept of loss and loss replacement as a means of gaining a fuller understanding of the implications of a diagnosis of epilepsy for overall quality of life (QOL). Potential participants were identified from the database of a large UK-based randomized controlled trial of antiepileptic drug treatment for new-onset epilepsy and selected using purposive sampling methods. In-depth interviews were conducted with 67 people; interview material was analyzed thematically. Our findings confirm 'loss' as a key concept in understanding epilepsy impact. Participants cited profound physical and social losses, and the links between these and psychological loss were clearly articulated. Informants described two main processes via which the linked losses they experienced occurred: personal withdrawal processes and externally enforced processes. Seizure control was integral to restoring psychological well-being and a sense of normality but was only one of a number of influences moderating the degree of loss experienced following seizure onset. Our work emphasizes that people with epilepsy (PWE) require active support for their continued engagement or reengagement in roles and activities identified as central to their psychological well-being and overall QOL. Achieving this requires a multiagency approach to drive forward key strategies for reduction of the negative impacts of epilepsy and to engender a sense of normality in the context of a condition often experienced as placing the individual outside the socially determined parameters of the 'normal'.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2014.02.015DOI Listing
April 2014

In response to comments on Parietal seizures mimicking psychogenic nonepileptic seizures.

Epilepsia 2014 Jan;55(1):197-8

Division of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital, Brown University, Providence, Rhode Island, U.S.A..

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12485DOI Listing
January 2014

Tools for assessing quality of life in epilepsy patients.

Expert Rev Neurother 2013 Dec 12;13(12):1355-69. Epub 2013 Nov 12.

Department of Public Health & Policy, University of Liverpool, Liverpool, L69 3GB, UK.

In this review, we attempt to bring the reader up to date with recent developments in the area of assessment of quality of life (QOL) of patients with epilepsy, in both the research and clinical contexts. We present evidence from recent publications on the major and most commonly used QOL instruments for both adults and children with epilepsy, including both strengths and limitations. We discuss both generic measures and ones that have been developed specifically for use in the epilepsy population. We draw attention to some of the broader issues that render the QOL assessment endeavor a somewhat complex one - in particular, that epilepsy is not a single condition, with a common clinical trajectory; and that QOL measures as currently configured almost universally focus on its negative impacts, largely neglecting the possibility of those affected being able to retain reasonable social adjustment and life satisfaction. Finally, we suggest that further work needs to focus on plugging the current evidence gaps in relation to psychometric and cross-cultural applicability issues; and on the value of QOL instruments in the clinical care setting. We conclude by highlighting a number of issues from the QOL literature that will, in our view, be the focus of increasing research interest in the next few years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1586/14737175.2013.850032DOI Listing
December 2013

Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force.

Epilepsia 2013 Nov 20;54(11):2005-18. Epub 2013 Sep 20.

Division of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital, Providence, Rhode Island, U.S.A; Departments of Psychiatry and Neurology (Research), Alpert Medical School of Brown University, Providence, Rhode Island, U.S.A.

An international consensus group of clinician-researchers in epilepsy, neurology, neuropsychology, and neuropsychiatry collaborated with the aim of developing clear guidance on standards for the diagnosis of psychogenic nonepileptic seizures (PNES). Because the gold standard of video electroencephalography (vEEG) is not available worldwide, or for every patient, the group delineated a staged approach to PNES diagnosis. Using a consensus review of the literature, this group evaluated key diagnostic approaches. These included: history, EEG, ambulatory EEG, vEEG/monitoring, neurophysiologic, neurohumoral, neuroimaging, neuropsychological testing, hypnosis, and conversation analysis. Levels of diagnostic certainty were developed including possible, probable, clinically established, and documented diagnosis, based on the availability of history, witnessed event, and investigations, including vEEG. The aim and hope of this report is to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12356DOI Listing
November 2013

Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6years.

Epilepsy Behav 2013 Nov 5;29(2):308-15. Epub 2013 Sep 5.

Neurology, Georgia Regents University, Augusta, GA, USA. Electronic address:

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System-Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2013.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902100PMC
November 2013
-->