Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus.

BACKGROUND: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied. METHODS: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death. RESULTS: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant. CONCLUSIONS: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).

Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6.

OBJECTIVE: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). METHODS: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. RESULTS: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1-56.8) years. Patients had discontinued a median (range) of 4 (0-15) antiseizure medications and were currently taking 3 (0-5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p < .049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. SIGNIFICANCE: Onset of treatment effect occurred within 6-10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16-week trial in most patients.

Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial.

BACKGROUND: Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. METHODS: In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075. FINDINGS: Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. INTERPRETATION: Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. FUNDING: National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.

OBJECTIVE: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline-recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second-line agent. RESULTS: Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second-line medications in these benzodiazepine-refractory seizures. SIGNIFICANCE: Benzodiazepines as first-line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.).

The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus.

The Established Status Epilepticus Treatment Trial was a blinded, comparative-effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine-refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight-based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight-normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54-1.51) or >90 kg (OR = 0.85, 95% CI = 0.42-1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings.

Valproate risk form-Surveying 215 clinicians involving 4775 encounters.

OBJECTIVES: Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications. MATERIALS AND METHODS: Study design-national online survey distributed to clinical specialists throughout the United Kingdom via their national organizations. Participants-clinicians qualified to counsel and administer the valproate RAF (as defined by the Medicines and Healthcare products Regulatory Agency). Main outcome measures-quantitative and qualitative responses regarding identification, uptake, effects and reactions to the RAF. Trial registration-registered at the Clinical Governance and Audit Committee at Royal Free London NHS Foundation Trust Hospital. RESULTS: 215 respondents covering more than 4775 patient encounters were captured. Most patients continued on valproate, 90% with epilepsy as the indication. Respondents reported that seizure control deteriorated when switched to levetiracetam (33%) and lamotrigine (43%), compared to 7% when continuing valproate (P < .001). CONCLUSIONS: 33%-43% of clinicians reported seizure control deterioration in women changed to alternatives to valproate. Informed consent requires women considering a change are given this information. Systematic capture of data automated through online RAFs and linked to patient outcomes is needed. There remains little data on valproate given for indications other than epilepsy.

Epilepsy deaths: Learning from health service delivery and trying to reduce risk.

Two recent UK reports have highlighted data of concern in relation to potentially preventable epilepsy deaths. Public Health England, an executive agency of the Government Department of Health, using National Health Service data from 2001 to 2014 reported a rise in direct age-standardised mortality for epilepsy-associated deaths, in contrast to a reduction in all-cause deaths over the same period. Premature death was seen in people aged below 50 years, especially in men, and where epilepsy was a contributory cause rather than an association. The Scottish Epilepsy Deaths Study, analysing deaths between 2009 and 2016, similarly found death in those with epilepsy was significantly higher than the matched population below the age of 54, especially between the ages of 16 and 24 (6 times higher). Sudden unexpected death in epilepsy accounted for 38% of epilepsy-related deaths under the age of 45. Both studies found a strong relationship between risk of death and deprivation; we discuss the implications of these and other data for planning service delivery and improving epilepsy care. This paper is for the Special Issue: Prevent 21: SUDEP Summit - Time to Listen.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

Brivaracetam in adults with drug-resistant epilepsy and psychiatric comorbidities.

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities who started on brivaracetam (BRV) at St George's University Hospitals and Frimley Health in London. Median BRV dose was 150 mg for a median follow-up period of 8 months. Twenty had focal epilepsy, four had generalized epilepsies, and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior, and 12% psychoses. Forty percent of patients presented at least 50% seizure reduction, but none of them became seizure-free. A total of 44% of patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy, and 4% because of both. Depression was reported by 8%, aggressive behavior by 8%, while 4% reported both. A total of 91.6% had received levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. Seventy-seven percent of patients who developed PAEs with LEV did not do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the synaptic vesicle glycoprotein 2A (SV2A) protein modulation is unlikely to be implicated in LEV-related PAEs.

Lessons from the Established Status Epilepticus Treatment Trial.

Convulsive status epilepticus (SE) is a relatively common emergency condition affecting individuals of all ages. The primary goal of treatment is prompt termination of seizures. Where first-line treatment with benzodiazepine has failed to achieve this, a condition known as established SE (ESE), there is uncertainty about which agent to use next. The Established Status Epilepticus Treatment Trial (ESETT) is a 3-arm (valproate (VPA), fosphenytoin (FOS), levetiracetam (LEV)), phase III, double-blind randomized comparative effectiveness study in patients aged 2 years and above with established convulsive SE. Enrollment was completed in January 2019, and the results are expected later this year. We discuss lessons learnt during the conduct of the study in relation to the following: ethical considerations; trial design and practical implementation in emergency settings, including pediatric and adult populations; quality assurance; and outcome determination where treating emergency clinicians may lack specialist expertise. We consider that the ESETT is already informing both clinical practice and future trial design. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Seizure-alerting behavior in dogs owned by people experiencing seizures.

INTRODUCTION: The unpredictability of epileptic seizures is considered an important threat to the quality of life of a person with epilepsy. Currently, however, there are no tools for seizure prediction that can be applied to the domestic setting. Although the information about seizure-alert dogs - dogs that display changes in behavior before a seizure that are interpreted by the owner as an alert - is mostly anecdotal; living with an alerting dog (AD) has been reported to improve quality of life of the owner by reducing the stress originating from the unpredictability of epileptic seizures and, sometimes, diminishing the seizure frequency. AIM OF THE STUDY: The aim of the study was to investigate, at an international level, the behaviors displayed by trained and untrained dogs that are able to anticipate seizures and to identify patient- and dog-related factors associated with the presence or absence of alerting behavior. METHODOLOGY: An online questionnaire for dog owners with seizures was designed. Information about the participants (demographics, seizure type, presence of preictal symptoms) and their dogs (demographics, behavior around the time of seizures) was collected. In addition, two validated scales were included to measure the human-dog relationship (Monash Dog-Owner Relationship scale (MDORS)) and five different traits of the dogs' personality (Monash Canine Personality Questionnaire refined (MCPQ-R)). RESULTS: Two hundred and twenty-seven responses of people experiencing seizures were received from six participant countries: 132 from people with dogs that had started alerting spontaneously, 10 from owners of trained AD, and the rest from owners of dogs that did not display any alerting behavior (nonalerting dog (NAD)). Individuals' gender, age, or seizure type did not predict the presence of alerting behavior in their dogs. People who indicated that they experience preictal symptoms were more likely to have a spontaneously AD. The owner-dog bond was significantly higher with ADs compared with NADs, and ADs scored significantly higher than NADs in the personality traits "Amicability", "Motivation", and "Training focus". CONCLUSION: This study collected a large group of dog owners with seizures reporting behavioral changes in their dogs before their seizures occurred. This was associated with the presence of preictal symptoms. The seizure-alerting behavior of the dog may have a positive influence on the bond between the owner and the dog.

Implementing clinical guidelines.

Clinical guidelines that support practice and improve care are essential in this era of evidence-based medicine. However, implementing this guidance often falls short in practice. Sharing knowledge and auditing practice are important, but not sufficient to implement change. This article brings together evidence from the study of behaviour, education and clinical practice and offers practical tips on how practising neurologists might bring about change in the healthcare environment. Common themes include the importance of team working, multidisciplinary engagement, taking time to identify who and what needs changing, and selecting the most appropriate tool(s) for the job. Engaging with the challenge is generally more rewarding than resisting and is important for the effective provision of care.

Vitamin D supplementation.

Vitamin D testing and supplementation is of great interest to neurologists and their patients. Recommended nutritional intakes of vitamin D in the UK remain focused on bone health, despite increasing evidence for a role outside this area. Here we discuss how neurologists might approach vitamin D testing and supplementation, focusing on two conditions associated with vitamin D deficiency that have an increased risk of downstream complications resulting from these: multiple sclerosis and epilepsy. We set out a rationale for testing serum 25-hydroxyvitamin D concentrations and discuss our personal practice in terms of supplementation, with evidence where available.

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

PURPOSE: To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. METHODS: Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. RESULTS: Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). CONCLUSIONS: One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

eLearning resources to supplement postgraduate neurosurgery training.

BACKGROUND: In an increasingly complex and competitive professional environment, improving methods to educate neurosurgical residents is key to ensure high-quality patient care. Electronic (e)Learning resources promise interactive knowledge acquisition. We set out to give a comprehensive overview on available eLearning resources that aim to improve postgraduate neurosurgical training and review the available literature. MATERIAL AND METHODS: A MEDLINE query was performed, using the search term "electronic AND learning AND neurosurgery". Only peer-reviewed English-language articles on the use of any means of eLearning to improve theoretical knowledge in postgraduate neurosurgical training were included. Reference lists were crosschecked for further relevant articles. Captured parameters were the year, country of origin, method of eLearning reported, and type of article, as well as its conclusion. eLearning resources were additionally searched for using Google. RESULTS: Of n = 301 identified articles by the MEDLINE search, n = 43 articles were analysed in detail. Applying defined criteria, n = 28 articles were excluded and n = 15 included. Most articles were generated within this decade, with groups from the USA, the UK and India having a leadership role. The majority of articles reviewed existing eLearning resources, others reported on the concept, development and use of generated eLearning resources. There was no article that scientifically assessed the effectiveness of eLearning resources (against traditional learning methods) in terms of efficacy or costs. Only one article reported on satisfaction rates with an eLearning tool. All authors of articles dealing with eLearning and the use of new media in neurosurgery uniformly agreed on its great potential and increasing future use, but most also highlighted some weaknesses and possible dangers. CONCLUSION: This review found only a few articles dealing with the modern aspects of eLearning as an adjunct to postgraduate neurosurgery training. Comprehensive eLearning platforms offering didactic modules with clear learning objectives are rare. Two decades after the rise of eLearning in neurosurgery, some promising solutions are readily available, but the potential of eLearning has not yet been sufficiently exploited.

Medical student perceptions of clinical neurosurgery teaching in an undergraduate medical school curriculum.

AIM: The aim of this study was to evaluate undergraduate medical student perceptions as to the value of different types of neurosurgical teaching to their general neuroscience education, delivered in the penultimate year of a U.K medical school. METHODS: We surveyed penultimate-year medical students at St George's Hospital Medical School, University of London (SGUL), who were undertaking their clinical neuroscience attachment from August 2014 to July 2015. A questionnaire comprising closed Likert scale questions and an open question inviting participants to comment freely was used to assess student perception about the value of Neurosurgical sessions within their overall neuroscience education. RESULTS: Of the 316 students in the year we surveyed 247 (78.2%), of whom 201 responded (response rate 81.4%). On average, 82.8% of students either agreed or strongly agreed that neurosurgical teaching sessions made a valuable contribution to their learning. In particular, lectures by neurosurgeons, clinical teaching on the Glasgow Coma Scale in neuro-ITU, bedside teaching and neurosurgical clinics were considered the most beneficial. The majority of students felt the sessions improved their understanding of neurological examination, signs, and 'red-flags'. The sessions were also beneficial for learning neuro-imaging and understanding of neurosurgical emergencies. Over two thirds felt that theatre sessions were beneficial, significantly more so amongst students invited to 'scrub-in'. CONCLUSIONS: Students rated neurosurgical sessions highly and valued the contribution they made not only to their learning of neurosurgical conditions and emergencies, but also to their learning of general neurology and clinical neurosciences overall. Student perceived learning from theatre sessions was significantly correlated with whether or not the student had been invited to 'scrub-in'. Expert neurosurgical teaching can make a valuable, and arguably essential contribution to the undergraduate medical curriculum.

Different attachment styles correlate with mood disorders in adults with epilepsy or migraine.

PURPOSE: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. METHODS: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). RESULTS: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p<0.001) and Preoccupation with relationships (p<0.001). Age correlated with the Relationships as secondary (r=0.322; p<0.001) and Need for approval (r=0.217; p=0.019) subscales while age at onset correlated only with Relationships as secondary (r=0.225; p=0.015). Seizure-free patients presented lower scores for Need for approval (p=0.003). Patients with migraine and a lifetime history of mood disorders presented lower scores in Confidence (p=0.002) and higher scores in Discomfort with closeness (p=0.026). CONCLUSIONS: An anxious-preoccupied attachment correlated with mood disorders in epilepsy while it was an avoidant pattern in migraine. Our results bring further data on the role of psychological variables in mood disorders in epilepsy. Further studies will allow early identification of patients at risk and the development of preventive strategies.

Depression correlates with quality of life in people with epilepsy independent of the measures used.

PURPOSE: A number of studies have suggested that depressed mood is one of the most important predictors of quality of life (QoL) in patients with epilepsy. However, the QoL measure used in previous studies was limited to the Quality of Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of QOLIE with measures of depression is influenced by the properties of the instruments used rather than being a valid effect. By using visual analogue scales, the current study aimed to clarify whether depression and QoL are truly correlated in patients with epilepsy. METHODS: Data from a sample of 261 outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley Outpatient Department, St George's Hospital in London, were analyzed. Patients were screened using the European Quality-of-Life scale (EQ-5D-3L) which includes an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), the Beck Depression inventory-II (BDI-II), the Hospital Anxiety and Depression scale (HADS), and the Major Depression inventory (MDI). RESULTS: Depression was found to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42 to 0.51 and r(2) coefficients ranging between 0.18 and 0.26. In addition, we identified patients who were depressed according to DSM-IV criteria (MD) and those with atypical forms of depression (AD). The EQ-5D-3L scores in these subjects compared with those without depression (ND) showed a different impact of AD and MD on QoL. CONCLUSIONS: The relationship between depression and QoL in people with epilepsy has been demonstrated to be a robust and valid effect, not a result of potential bias of the specific measures used. However, the strength of the association is influenced by the individual instrument. Atypical or subsyndromic forms of depression are as relevant as DSM-based depression in terms of impact on QoL.

Stress and epilepsy: fact or fiction, and what can we do about it?

People with epilepsy report that stress is their most common trigger for seizures and some believe it caused their epilepsy in the first place. The extensive preclinical, epidemiological and clinical studies examining the link between stress and epilepsy have given confusing results; the clinical studies in particular are fraught with confounders. However stress is clearly bad for health, and we now have substantial preclinical evidence suggesting that chronic stress worsens epilepsy; in selected cases it may even be a causal factor for epilepsy. Healthcare professionals working with people with epilepsy should pay more attention to stress in clinical practice. This review includes some practical advice and guidance for stress screening and management.