Ten things every neurologist needs to know about neuropsychological assessments and interventions in people with epilepsy.

This paper describes 10 core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the following headings. (1) A neuropsychological assessment is a collaborative investigation. (2) Assessment prior to treatment allows for the accurate assessment of treatment effects. (3) The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. (4) Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. (5) Patients' subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. (6) The results from a neuropsychological assessment can be used to maximize the educational and occupational potentials of people with epilepsy. (7) Not all patients are able to engage with a neuropsychological assessment. (8) There are limitations in assessments conducted in a second language with tests that have been standardized on different populations from that of the patient. (9) Adequate intervals between assessments maximize sensitivity to meaningful change. (10) Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.

The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding.

Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014. This Conference Proceedings provides a summary of the conference proceedings. Specifically, the following topics are discussed: (i) role of comorbidities in epilepsy diagnosis and management, (ii) role of antiepileptic medications in understanding the relationship between epilepsy and neurobehavioral and cognition problems, and (iii) animal data and diagnostic approaches. Evidence to date, though limited, strongly suggests a bidirectional relationship between epilepsy and cognitive and psychiatric comorbidities. In fact, it is likely that seizures and neurobehavioral problems represent different symptoms of a common etiology or network-wide disturbance. As a reflection of this shared network, psychiatric comorbidities and/or cognition problems may actually precede the seizure occurrence and likely get often missed if not screened.

Disentangling the relationship between epilepsy and its behavioral comorbidities - the need for prospective studies in new-onset epilepsies.

It has been long recognized that there is more to epilepsy than seizures. The prevalence of such neurobehavioral abnormalities as cognitive and mood disorders, autism spectrum disorder, and attention deficit and hyperactivity disorder (ADHD) is significantly higher among patients with epilepsy than in the general population. A long-held view that comorbidities of epilepsy represent mere epiphenomena of seizures has undergone substantial transformation during the past decade, as emerging clinical evidence and experimental evidence suggest the involvement of specific neurobiological mechanisms in the evolution of neurobehavioral deficits in patients with epilepsy. Developmental aspects of both epilepsy and its comorbidities, as well as the frequently reported reciprocal connection between these disorders, both add other dimensions to the already complex problem. In light of progress in effective seizure management in many patients with epilepsy, the importance of neurobehavioral comorbidities has become acute, as the latter are frequently more detrimental to patients' quality of life compared with seizures. This calls for a serious increase in efforts to effectively predict, manage, and ideally cure these comorbidities. Coordinated multicenter clinical, translational, and basic research studies focusing on epidemiology, neuropsychology, neurophysiology, imaging, genetics, epigenetics, and pharmacology of neurobehavioral comorbidities of epilepsy are absolutely instrumental for ensuring tangible progress in the field. Clinical research should focus more on new-onset epilepsy and put particular emphasis on longitudinal studies in large cohorts of patients and groups at risk, while translational research should primarily focus on the development of valid preclinical systems which would allow investigating the fundamental mechanism of epilepsy comorbidities. The final goal of the described research efforts would lie in producing an armamentarium of evidence-based diagnostic tools and therapeutic interventions which would at minimum mitigate and at maximum prevent or abolish neurobehavioral comorbidities of epilepsy and, thus, improve the quality of life of those patients with epilepsy who suffer from the said comorbidities.

Differential effects of antiepileptic drugs on neonatal outcomes.

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

The behavioral consequences of exposure to antiepileptic drugs in utero.

The aim of the study was to examine the behavior of 242 children, aged between 6 and 16 years, born to mothers with epilepsy. Exposure to sodium valproate (VPA) in utero was associated with high levels of parental stress induced by the child's maladaptive behavior. These children were also poorer for daily living skills and skills relating to socialization. The outcomes on both measures were strongly affected by the Full Scale IQ (FSIQ) of the child; however, no significant differences were found between the groups and therefore this pattern of results cannot simply be attributed to a lower FSIQ. The results of this study suggest that exposure to VPA in utero and the presence of a lowered FSIQ are risk factors for the development of poorer adaptive behavior and a higher rate of maladaptive behaviors.

Knowledge gaps and uncertainties about epilepsy: findings from an ethnographic study in China.

Epilepsy represents one of the major brain disorders worldwide. In China, research into how much people with epilepsy know about their condition appears limited. Drawing on data collected as part of a large ethnographic study, we present the experiences and views of Chinese people with epilepsy and their family members, to identify knowledge gaps and uncertainties about epilepsy within selected urban and rural communities. We also examine how respondents' demographic characteristics influence their knowledge, understanding, and beliefs about epilepsy. We found knowledge and understanding of epilepsy to be uneven and context specific. Hereditary factors were most frequently cited as a potential cause, although their impact remained unclear. Western medicalization of epilepsy appears less evident in the reports of rural informants, where traditional beliefs continue to shape definitions and treatment. Societal differences within these communities set boundaries on knowledge acquisition. Plotted against these differences, we suggest strategies for proposed educational/psychosocial intervention programs.

Glycerol Hydrogen-Bonding Network Dominates Structure and Collective Dynamics in a Deep Eutectic Solvent.

The deep eutectic solvent glyceline formed by choline chloride and glycerol in 1:2 molar ratio is much less viscous compared to glycerol, which facilitates its use in many applications where high viscosity is undesirable. Despite the large difference in viscosity, we have found that the structural network of glyceline is completely defined by its glycerol constituent, which exhibits complex microscopic dynamic behavior, as expected from a highly correlated hydrogen-bonding network. Choline ions occupy interstitial voids in the glycerol network and show little structural or dynamic correlations with glycerol molecules. Despite the known higher long-range diffusivity of the smaller glycerol species in glyceline, in applications where localized dynamics is essential (e.g., in microporous media), the local transport and dynamic properties must be dominated by the relatively loosely bound choline ions.

A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial.

OBJECTIVES: To compare clinicians' choice of one of the standard epilepsy drug treatments (carbamazepine or valproate) versus appropriate comparator new drugs. DESIGN: A clinical trial comprising two arms, one comparing new drugs in carbamazepine and the other with valproate. SETTING: A multicentre study recruiting patients with epilepsy from hospital outpatient clinics. PARTICIPANTS: Patients with an adequately documented history of two or more clinically definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option. INTERVENTIONS: Arm A was carbamazepine (CBZ) versus gabapentin (GBP) versus lamotrigine (LTG) versus oxcarbazepine (OXC) versus topiramate (TPM). Arm B valproate (VPS) versus LTG versus TPM. MAIN OUTCOME MEASURES: Time to treatment failure (withdrawal of the randomised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two) and time to achieve a 12-month remission of seizures. Time from randomisation to first seizure, 24-month remission of seizures, incidence of clinically important adverse events, quality of life (QoL) outcomes and health economic outcomes were also considered. RESULTS: Arm A recruited 1721 patients (88% with symptomatic or cryptogenic partial epilepsy and 10% with unclassified epilepsy). Arm B recruited 716 patients (63% with idiopathic generalised epilepsy and 25% with unclassified epilepsy). In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC. Some 12% and 8% fewer patients experienced treatment failure on LTG than CBZ, the standard drug, at 1 and 2 years after randomisation, respectively. The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinically inferior to CBZ for measures of its efficacy. No consistent differences in QoL outcomes were found between treatment groups. Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality-adjusted life-year gained. In Arm B for time to treatment failure, VPS, the standard drug, was preferred to both TPM and LTG, as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission. QoL assessments did not show any between-treatment differences. The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy, although there is a suggestion that TPM is a cost-effective alternative to VPS. CONCLUSIONS: The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing standard drug treatment, CBZ, for patients diagnosed as having partial seizures. For patients with idiopathic generalised epilepsy or difficult to classify epilepsy, VPS remains the clinically most effective drug, although TPM may be a cost-effective alternative for some patients. Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy (levetiracetam, zonisamide and pregabalin), therefore these drugs should be compared in a similarly designed trial.

Treatments for non-epileptic attack disorder.

BACKGROUND: Psychogenic non-epileptic seizures (NES) have the outward appearance of epilepsy in the absence of physiological or electroencephalographic correlates. Non-epileptic seizures can occur in isolation or in combination with epileptic seizures. The development and maintenance of non-epileptic seizures has been well documented and there is a growing literature on the treatment of NES which includes non-psychological (including anti-anxiety and antidepressant pharmacological treatment) and psychological therapies (including cognitive behavioural therapy (CBT), hypnotherapy and paradoxical therapy). Various treatment methodologies have been tried with variable success. The purpose of this Cochrane review was to establish the evidence base for the treatment of NES. OBJECTIVES: To assess whether treatments for NES result in a reduction in frequency of seizures and/or improvement in quality of life, and whether any treatment is significantly more effective than others. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialised Register (September 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to July 2005), and PsycINFO (1806 to July 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies SELECTION CRITERIA: Randomised or quasi-randomised studies were included that assessed one or more types of psychological or non-psychological interventions for the treatment of NES. Studies of childhood NES were excluded from our review. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the trials for inclusion and extracted data. Outcomes included reduction in seizure frequency and improvements in quality of life. MAIN RESULTS: Three small studies met our inclusion criteria and were of poor methodological quality. Two assessed hypnosis and the other paradoxical therapy. There were no detailed reports of improved seizure frequency or quality of life outcomes, and these trials provide no reliable evidence of a beneficial effect of these interventions. AUTHORS' CONCLUSIONS: In view of the methodological limitations and the small number of studies, we have no reliable evidence to support the use of any treatment including hypnosis or paradoxical injunction therapy in the treatment of NES. Randomised studies of these and other interventions are needed.

Self-management education for adults with epilepsy.

BACKGROUND: Self-management education has been shown to improve the quality of life of people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for adults with epilepsy. SEARCH STRATEGY: We searched MEDLINE (Ovid) (1966 to April 2005), EMBASE (Ovid) (1980 to April 2005), CINAHL (Dialog) (1980 to April 2005), PsycINFO (Dialog) (1887 to April 2005), and the Cochrane Epilepsy Group's Specialised Register (April 2005). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. We did not impose any language restriction. We re-ran the searches in February 2007 and added the identified references to the 'Studies awaiting assessment' table. SELECTION CRITERIA: Randomised trials of self-management education programmes for adults with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Two trials evaluated the effect of self-management education for adults with epilepsy, neither of which assessed as being of high quality. In total, 483 adults with epilepsy were randomised. Both trials showed improvements in seizure frequency and other outcomes, such as knowledge. However, we were not able to estimate a summary effect for seizure frequency due to a lack of data. AUTHORS' CONCLUSIONS: Self-management education programmes, based on increasing understanding through psychosocial methods, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency. It is, however, not clear how effective self-management programmes of epilepsy would be in a more general population of adults with epilepsy, as both trials had higher proportions of people with partial seizures than would be expected in a community sample.

Self-management education for children with epilepsy.

BACKGROUND: Self-management education has been shown to improve the quality of life of children and young people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in children and young people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for children and young people with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialised Register (April 2007), MEDLINE (Ovid) (1966 to February 2007), EMBASE (Ovid) (1980 to February 2007), CINAHL (Dialog) (1980 to February 2007), and PsycINFO (Dialog) (1887 to February 2007). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. No language restriction was imposed. SELECTION CRITERIA: Randomised trials of self-management education programmes for children or young people with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Only one trial involving 167 children was identified that evaluated the effect of a child-centred model of training for the self-management of two chronic illnesses, asthma and epilepsy. The trial was not assessed as being of high quality and the methods used to analyse and report the data did not enable us to precisely determine the effect of the intervention. However, improvements were seen in seizure frequency and other outcomes, such as knowledge and behaviour. AUTHORS' CONCLUSIONS: Self-management education programmes that deliver a child-centred model of training, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency in children and young people with epilepsy. However, based on the evidence reviewed, we are not able to determine how effective it is, or what the key components of the programme should be.

Sensitivity of the UK Clinical Practice Research Datalink to Detect Neurodevelopmental Effects of Medicine Exposure in Utero: Comparative Analysis of an Antiepileptic Drug-Exposed Cohort.

INTRODUCTION: Electronic healthcare data have several advantages over prospective observational studies, but the sensitivity of data on neurodevelopmental outcomes and its comparability with data generated through other methodologies is unknown. OBJECTIVES: The objectives of this study were to determine whether data from the UK Clinical Practice Research Datalink (CPRD) produces similar risk estimates to a prospective cohort study in relation to the risk of neurodevelopmental disorders (NDDs) following prenatal antiepileptic drug (AED) exposure. METHODS: A cohort of mother-child pairs of women with epilepsy (WWE) was identified in the CPRD and matched to a cohort without epilepsy. The study period ran from 1 January 2000 to 31 March 2007 and children were required to be in the CPRD at age 6 years. AED exposure during pregnancy was determined from prescription data and children with an NDD diagnosis by 6 years were identified from Read clinical codes. The prevalence and risk of NDDs was calculated for mother-child pairs in WWE stratified by AED regimen and for those without epilepsy. Comparisons were made with the results of the prospective Liverpool and Manchester Neurodevelopment Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years. RESULTS: In the CPRD, 1018 mother-child pairs to WWE and 6048 to women without epilepsy were identified. The CPRD identified a lower prevalence of NDDs than the prospective study. In both studies, NDDs were more frequently reported in children of WWE than women without epilepsy, although the CPRD risk estimate was lower (2.16 vs. 0.96%, p < 0.001 and 7.46 vs. 1.87%, p = 0.0128). NDD prevalence differed across AED regimens but the CPRD data did not replicate the significantly higher risk of NDDs following in utero monotherapy valproate exposure (adjusted odds ratio [ORadj] 2.02, 95% confidence interval [CI] 0.52-7.86) observed in the prospective study (ORadj 6.05, 95% CI 1.65-24.53). CONCLUSION: It was possible to identify NDDs in the CPRD; however, the CPRD appears to under-record these outcomes. Larger studies are required to investigate further.

Psychological treatments for epilepsy.

BACKGROUND: Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. OBJECTIVES: To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), and MEDLINE (1966 to March 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. MAIN RESULTS: We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies. AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited number of individuals studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.

The detection of malingering in memory performance: the sensitivity and specificity of four measures in a UK population.

OBJECTIVES: To investigate the validity of a clinical neuropsychological battery for the detection of malingering on tests of memory. METHODS: A simulated scenario design was developed to investigate the effectiveness of a battery of four neuropsychological tests in the detection of malingering; the Coin in the Hand Test (CIH), Autobiographical Memory Index (AMI), Rey I 5-Item Test (RIT),and the Wechsler Mental Control Test (MCT). The performances of patients with an acquired brain injury (N = 40) were compared with two groups of controls instructed either to simulate a head injury performance (N = 40) or do their best (N = 40). RESULTS: The CIH and MCT demonstrated good validity and displayed high sensitivity and specificity. The RIT and the AMI was relatively poor in distinguishing between simulators and patients. CONCLUSIONS: The sensitivity and specificity of all four tests to the detection of malingering has been assessed. Two of the tests the CIH and MCT would be useful as a quick and accurate screening tool for detecting malingering.

Effect of psychotropic agents upon the blastogenic response of human t-lymphocytes.

Antischizophrenic agents, phenothiazine and nonphenothiazine, inhibit the transformation of the T-lymphocyte in vitro. This inhibition occurs only in the early event and is neither competitive with dopamine, nor appears to involve Na+/K+ adenosine triphosphatase. RNA synthesis is more sensitive to the inhibitory effect than DNA or protein synthesis. This leads to the conclusion that chlorpromazine may act by inhibiting the synthesis of newly formed RNA, and subsequently, transformation, rather than by alteration of the cell membrane.

Health-related quality-of-life issues: optimizing patient outcomes.

Quality of life has emerged as an important health care outcome for patients with chronic illnesses requiring long-term therapy. Disease-specific quality-of-life instruments have been developed as outcome measures for several chronic diseases, and the number of studies that have used quality of life as an outcome measure has increased dramatically in the past 10 years. Quality-of-life measures have not been widely applied in epilepsy, however. Because seizure severity is an important measure of quality of life, seizure severity scales that quantify seizure severity in the evaluation of medical and surgical treatments of epilepsy have been developed for use in clinical trials. The development of a health-related quality-of-life model for epilepsy, including previously validated scales, and its application to the assessment of treatment effects in a clinical trial are described.

Significance of radiocontaminants in 123I for dosimetry and scintillation camera imaging.

Estimates of absorbed radiation dose and qualitative assessments of image resolution were compared for pure 131I and for 123I produced by the 122Te(d,n), 124Te(p,2n), and 127I(p,5n) 123Xe reactions. A substantial reduction in radiation dose is indicated when 123I replaces 131I, in spite of the radiocontaminants typically present 30-35 hr after the production of 123I by any of these methods. Only a marginal further reduction in radiation dose was noted with use of the most "pure" 123I as opposed to the least "pure" 123I. Comparable scintillation camera resolution was obtained for all 123I preparations at 30-35 hr after bombardment when the medium-energy and pinhole collimators were used. However, the radiocontaminants in the 123I produced from tellurium affected image resolution when the low-energy collimator was used.

Quality of life and epilepsy: the Liverpool experience.

The use of quality of life (QOL) measures in epilepsy research is relatively recent compared with that in other chronic conditions such as coronary heart disease and diabetes. However, in recent years much research has been undertaken to develop and validate QOL measures for use in various groups of people with epilepsy, including children, the elderly, and newly diagnosed patients. QOL measures are now available for use in both clinical trials and primary care. The Liverpool Group is one of the leading research teams in this field and is probably best known for developing the Liverpool Seizure Severity Scale. However, the group has also developed a number of other QOL measures, with an emphasis on keeping the measures appropriate, practical, and responsive, and always considering the burden to patients. This review describes some of the measures the Liverpool Group has developed, outlines their application in clinical trials of a number of aspects of antiepileptic drugs, and details the importance of some of the findings. The diversity of the group's approach and of its involvement in assessing the QOL of people with epilepsy are emphasized.

The Neurotoxicity Scale--II. Results of a patient-based scale assessing neurotoxicity in patients with epilepsy.

The Neurotoxicity Scale was devised as a patient-based report scale to assess the adverse effects of antiepileptic drugs on cognitive function. In a previous report we reported the clinical validity of the scale, tested in a double-blind randomized study, using a benzodiazepine in normal volunteers. In the present study, the clinical sensitivity, construct validity and reliability of the scale was tested in patients with epilepsy. Patients (n = 189), selected from both participating centres, representative for the patients with chronic epilepsy were included in the study. Reliability was tested with Cronbachs alpha and yields an almost maximal score (.95). Clinical sensitivity was compared with the previous normal volunteer study and was evaluated as satisfactory. Construct validity showed a five-factor structure, explaining 66.5% of the variance, with 'fatigue and slowing' as the dominant factor. In line with the assumptions for this scale and with the results obtained in normal volunteers, the scale appears to be unsuitable for differential assessment of type or severity of drug-induced impairment. The most valid primary outcome measure is the overall score that renders a global ('all or nothing') evaluation indicating that a subject experiences cognitive impairment and associates this with the antiepileptic treatment. Other factors that may impair cognitive function, such as seizure frequency do not influence this score. The scale has therefore maximal applicability as a screening instrument in outpatient practice and in early (phase II, IIIa) drug trials.

Cognitive and behavioural assessments in clinical trials: what type of measure?

This paper provides an overview of the types of neuropsychological and behavioural measures used in randomised controlled trials (RCTS) of antiepileptic drugs (AEDs) in patients with epilepsy. The results of previous systematic reviews are reported in respect of the methods used in clinical trials to assess cognitive and behavioural effects of AED treatment. There were 46 trials incorporating behavioural measures and 40 trials incorporating neuropsychological measures. The evidence supporting the choice of test, and their reliability, validity, and sensitivity to change was minimal. It is concluded that poor reporting of methods and a plethora of both neuropsychological and behavioural measures make it difficult to provide any meaningful comments about the effects of AED treatment. A much more standardised approach to assessing these effects is necessary.