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This review examines the clinical and neuroradiological features of traumatic brain injury that are most frequently associated with persistent cognitive complaints. Neuropsychological outcomes do not depend solely on brain injury severity but result from a complex interplay between premorbid factors, the extent and nature of the underlying structural damage, the person’s neuropsychological reserve and the impact of non-neurological factors in the recovery process. Brain injury severity is only one of these factors and has limited prognostic significance with respect to neuropsychological outcome. We examine the preinjury and postinjury factors that interact with the severity of a traumatic brain injury to shape outcome trajectories. We aim to provide a practical base on which to build discussions with the patient and their family about what to expect following injury and also to plan appropriate neurorehabilitation.

Objective Problem gambling results from the complex interaction of neurological factors with psychological, demographic, and socioeconomical influences. The vulnerabilities of people with epilepsy to many of these influences may increase their susceptibility to developing problematic gambling behaviors. The aim of this study was to establish the frequency of gambling participation and the clinical correlates of problem gambling behaviors in people with epilepsy. Methods Lifestyle questions, including the Lie/Bet screening questionnaire were administered to 250 consecutive attendees at a neurology clinic. Valid data were available for 174 adults with epilepsy and 65 adults with other neurological conditions. Results With the exception of people with frontal lobe epilepsy (FLE), gambling participation rates in people with epilepsy and those with other neurological conditions were lower than those reported in the general population. While the overall levels of gambling participation were relatively low in this sample, the number of gamblers who responded positively to the lie/bet questionnaire was ten times higher than that seen in the general population, with one in three gamblers in our series reporting signs of escalation. All had epilepsy and were more likely to be taking Levetiracetam or Brivaracetam than the other gamblers in our series. While epilepsy classification was not related to gambling escalation, patients with FLE were overrepresented in this group due to their significantly higher baseline levels of participation in gambling. Conclusions People with FLE may have a heightened vulnerability to developing problem gambling behaviors. The role of the neurological consultation in managing these risks is discussed.

Objectives To investigate the clinical characteristics, final diagnosis, investigation results, management, response to anti-seizure medications (ASMs) and clinical outcomes of individuals assessed in a First Seizure service over a 5-year period. Methods Retrospective analysis of 772 individuals who were clinically assessed in a dedicated First Seizure service at National Hospital for Neurology & Neurosurgery (NHNN), Queen Square over a 5-year period. Results 772 individuals were assessed following a suspected or reported first seizure (median age of 54, average age of 39.4, range 16–96). 393 (50.9 %) were ultimately diagnosed with a definite seizure of which 183 (46.5 %) had experienced seizures previously which had not been recognised or diagnosed. 250 (32 %) had vasovagal syncope and 69 (18.2 %) were diagnosed with psychogenic non-epileptic seizures. EEGs in 16.6 % of individuals who had a first unprovoked seizure demonstrated epileptiform discharges, whilst 33.6 % had abnormal MRI findings felt to be clinically relevant. Conclusions Seizure mimics represent a significant proportion of attendees to a ‘first seizure’ service. Improved recognition and more education of this issue could facilitate earlier management of these other diagnostic entities and ensure that only appropriate cases are referred to the first seizure service. Almost half of ‘first seizure’ cases had previous seizures, highlighting the importance of obtaining this relevant history and in reviewing ASM-naive individuals in a timely manner with the primary aim of preventing further recurrences.

Cognitive complaints in people with epilepsy are usually multifactorial in their nature and origin. While antiepileptic medications are an important consideration, we explore other ways in which neurologists can address cognitive problems in this population. It is never too early to ask about cognitive impairment, and the answers can have diagnostic significance. Understanding and accepting that cognitive problems may result, at least in part, from the same pathological process that generates seizures is an important part of the rehabilitation process. Patients referred for neurorehabilitation for cognitive difficulties who have realistic expectations and goals tend to benefit more from the intervention than those expecting a cure. Developing an understanding of this and managing patient expectations should start in the neurology clinic. Although we focus primarily on memory function, the principles we discuss in this paper apply to the broad spectrum of cognitive and neurobehavioral problems that accompany the many diagnoses of epilepsy.

BackgroundBright light therapy is an effective treatment for seasonal affective disorder and non-seasonal depression. Depression and anxiety are common psychiatric comorbidities in epilepsy.AimsTo examine the efficacy of bright light therapy for symptoms of anxiety and depression in adults with focal epilepsy (trial registration at ClinicalTrials.gov: NCT01028456).MethodWe recruited 101 adults with medically intractable focal epilepsy. Participants completed the Hospital Anxiety and Depression Scale (HADS) at the beginning (T1) and end of a 12-week baseline period (T2) and again after 12 weeks of daily light therapy (T3), with 51 participants using a high-intensity light box and 50 using a low-intensity one. Seizure diaries were kept throughout the baseline and trial period.ResultsA total of 58 patients completed the trial. Anxiety and depression scores were significantly reduced following the light therapy at T3in both the high- and low-intensity groups.ConclusionsLight therapy resulted in a significant reduction in symptoms of anxiety and depression but we did not find any differences between high- v. low-intensity treatment This may, therefore, be an effective treatment for symptoms of low mood in epilepsy at lower intensities than those typically used to treat seasonal affective disorder. Further work is needed to investigate this possibility with an adequate placebo condition.

Background Bright light therapy (BLT) influences the regulation of melatonin and is an established treatment for seasonal affective disorder (SAD). This study was designed to examine the efficacy of BLT for seizure control in adults with focal epilepsy. Design 101 adults with medically intractable focal epilepsy were recruited to a parallel-design, double-blind, randomized trial of BLT as an add on treatment for epilepsy. Methods All patients monitored their seizure frequency at home for a 12‐week baseline period (September 2010 to December 2010). 51 of the participants were allocated with a high-intensity (HI) light box emitting 10,000 lx using an automated permuted block randomization grid. 50 were allocated with a cosmetically identical box emitting 2000 lx (low-intensity — LI), a subtherapeutic dose in other patient populations. Both groups were instructed to use their box for 20–30 min, upon waking every day for 12 weeks (January–March 2011). The primary outcome measure for the trial was seizure frequency. Results 77 participants (39 high-intensity/38 low-intensity) completed the trial and returned adequate data for analyses. Median reduction of seizures during the treatment phase was 1.5 in the LI group and 3 in the HI group (p > 0.05). 6 patients (15%) in the high-intensity condition experienced an overall reduction of 50% or more in the frequency of complex partial seizures compared to 9 (24%) patients who used the low intensity light box. Response rates in the HI and LI treatment conditions were not significantly different (p > 0.05). Patients with hippocampal sclerosis were more likely to respond to BLT at either intensity than patients with other focal epilepsies (risk ratio = 1.7 95% CI lower limit = 0.6, upper limit = 4.6). Conclusions We did not find a significant difference in the responder rates in the low- vs. high-intensity arms of the trial. Some patterns within the data suggest that BLT may warrant further investigation as a treatment for people with hippocampal pathology. Our initial findings suggest that caution should be exercised in using BLT in people with extra temporal focal epilepsy as it may result in an increase in seizures for some.

Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trials, few studies have addressed long-term outcome in large groups of patients. A cohort of patients attending a tertiary referral centre for epilepsy was identified as having started taking PGB. Patients' data were obtained through medical records. Of 402 patients included, 42% of patients were still taking PGB at last follow-up. The estimated 2.5-year retention rate was 32%. Males appeared more likely to continue on PGB therapy than females. The common adverse experiences (AEs) leading to withdrawal were CNS-related, psychiatric AEs and weight gain. Published retention rates for levetiracetam appear to be higher, and those for gabapentin lower, than the rates estimated for PGB.

The decision to treat or not treat individuals who have suffered a single epileptic seizure is based on clinical factors, which are considered within the individual's social, cultural, and emotional environment. Even if optimally communicated, individuals and their carers will make different decisions about first seizures and their treatment, as they will judge the risks and benefits of treatment (or its deferment) in this wider context. There is a significant body of literature that describes the impact of established epilepsy on aspects of an individual's overall quality of life (QoL), and more recently evidence is emerging about the factors that may be important in 2 years after a single seizure on and off treatment. Little research, however, has considered the importance of nonclinical factors in individual's choices at the time of a first seizure, and in particular in an individual's decision to use or not use treatment. Understanding these issues may improve communication of risks and benefits to individuals, and may offer insight into the mechanisms by which social and socioeconomic disadvantage occur in epilepsy.

Summary Background Intravenous steroids are routinely used to treat disabling relapses in multiple sclerosis, and can be administered in an outpatient or home setting. We developed a rating scale that allowed us to compare the two strategies formally in a trial setting. Methods Patients who had a clinically significant multiple-sclerosis relapse within 4 weeks of onset were randomly assigned administration of a 3-day regimen of intravenous methylprednisolone either in an outpatient clinic (n=69) or at home (n=69). The MS relapse management scale (MSRMS) was developed to measure patients' experiences of relapse management as the primary outcome. Efficacy of the two treatment modalities was compared in terms of traditional measures and economic cost. A cost-minimisation analysis was also done. Analysis was by intention to treat. Findings Of 149 eligible patients, 138 consented to participate in the trial and were randomly assigned to a treatment group. Coordination of care was significantly better in the home-treatment group (median score 4·5 [IQR 3·0–11·4]) than in the hospital-treatment group (12·1 [3·0–18·6]; p=0·024). The other dimensions of the MSRMS did not differ between groups (p>0·10). Administration of steroids was equally safe and effective in either location, and cost was either the same or cheaper when delivered at home than when delivered in hospital. Interpretation Treatment of relapses in multiple sclerosis with intravenous steroids can be effectively and safely administered at home, from both patient and economic perspectives. Moreover, the trial indicates the importance of explicit and valid outcome measures of all aspects of service delivery when making decisions about health policy. This finding has implications for complex service delivery care models for long-term diseases.

Carbamazepine is widely recommended as a first-line antiepileptic drug for new-onset partial seizures with or without generalization. Branded carbamazepine remains commonly prescribed. Newer antiepileptic drugs have higher acquisition costs than carbamazepine, but may offer advantages in terms of tolerability and side-effect profile that may offset their additional cost. Furthermore, generic carbamazepine is often cheaper than branded forms, and many argue for a policy of prescribing the cheapest available generic form. This study reviews the scant health economic data concerning the use of carbamazepine to treat epilepsy to establish whether use of this drug is cost effective. Carbamazepine would appear to be a cost-effective treatment for epilepsy in certain contexts, although evidence from a prospective, randomized, controlled trial is awaited and this assertion may not be true for certain patient subgroups, or in developing world health services. Furthermore, at this time there is insufficient evidence to support policies of cheapest generic or brand-only prescribing.

We describe a 38-year-old woman with a predominantly sensory axonal polyneuropathy in whom a nerve biopsy demonstrated sarcoid granulomas. The neuropathy did not respond to oral steroid therapy but there was a rapid and repeated response to intravenous immunoglobulin, which gradually diminished over subsequent treatments, but remained beneficial. The systemic sarcoidosis remained active.

Objective: To determine the incidence of epilepsy in a general practice population and its variation with socioeconomic deprivation. Design: Prospective surveillance for new cases over an 18 or 24 month period. Participants: All patients on practice registers categorised for deprivation with the Carstairs score of their postcode. Setting: 20 general practices in London and south east England. Main outcome measure: Confirmed diagnosis of epilepsy. Results: 190 new cases of epilepsy were identified during 369 283 person years of observation (crude incidence 51.5 (95% confidence interval 44.4 to 59.3) per 100 000 per year). The incidence was 190 (138 to 262) per 100 000 in children aged 0-4 years, 30.8 (21.3 to 44.6) in those aged 45-64 years, and 58.7 (42.5 to 81.0) in those aged 65 years. There was no apparent difference in incidence between males and females. The incidence showed a strong association with socioeconomic deprivation, the age and sex adjusted incidence in the most deprived fifth of the study population being 2.33 (1.46 to 3.72) times that in the least deprived fifth (P=0.001 for trend across fifths). Adjustment for area (London v outside London) weakened the association with deprivation (rate ratio 1.62 (0.91 to 2.88), P=0.12 for trend). Conclusions: The incidence of epilepsy seems to increase with socioeconomic deprivation, though the association may be confounded by other factors. What is already known on this topic Epilepsy is associated with a wide range of markers of social and economic disadvantage A small number of epidemiological studies have confirmed this association but have not established the direction of causality What this study adds The incidence of epilepsy, adjusted for age and sex, in the most deprived fifth of the study population was 2.3 times that in the least deprived fifth Socioeconomic deprivation is an important risk factor for the development of epilepsy, though the results may partly reflect differences in incidence within and outside London

Objective In the general population, obesity is associated with accelerated age-related cognitive decline. The impact of obesity on cognitive function in neurological populations who already have a heightened risk of cognitive decline is unknown. This study explored the relationship between obesity and cognitive underfunction in people with medically intractable epilepsy. Methods Eighty-one consecutive patients admitted for evaluation for medically intractable epilepsy (36 females and 45 males) underwent tests of memory and intellectual function. Optimal level of function was assessed using the National Adult Reading Test — Revised. Measures of underfunction were calculated by subtracting current measures of intellectual ability from the NART IQ. Body mass index (BMI) was used as an index of obesity. Results Twenty-nine people had a BMI in the healthy range (36%), 31 were overweight (38%), and 21 were obese (26%). The healthy weight, overweight, and obese groups did not differ in age at the time of assessment, age at seizure onset, or optimal level of function (NART IQ). The obese group had a greater degree of suboptimal processing speed and demonstrated a greater degree of underfunction on the Full Scale IQ (FSIQ) measure compared to the healthy weight group. Body mass index accounted for 14% of the variance in underfunction in processing speed and 10% of the variance in underfunction in FSIQ. Controlling for the effects of age, all measures of memory function were significantly correlated with BMI, with poorer scores associated with higher BMIs. Significance A small but significant proportion of the variance in memory function and intellectual underfunction in people with epilepsy is explained by BMI. Further work is needed to establish whether a reduction in BMI to within healthy limits is associated with improvements in cognitive function in this group.

To observe the degree to which prices for medical services and anti-epileptic drugs (AEDs) vary between eight European Union (EU) countries, to identify the factors that are likely to contribute to these variations and to consider the validity of international cost-of-illness comparisons. Cost-of-illness study methodology has been used to estimate the national cost of epilepsy in several developed countries. The validity of comparing these studies is unknown. Eight EU member countries were selected. Charges and prices were obtained for important aspects of medical care of patients with epilepsy including AEDs. The perspective taken was that of the major health care payer within each country. Prices were validated by a local panel of doctors expert in treating epilepsy. Prices for similar services were compared between countries. Charges and prices levied to health service payer vary widely between the eight countries considered. The cheapest and most expensive medical services vary by as much as 24 times, whereas the price of AED varies up to 4.4 times. These wide variations suggest that prices do not reflect the true cost of providing these important aspects of epilepsy treatment. International comparisons between national cost-of-illness estimates relying on such prices should be interpreted with caution.

We undertook an economic appraisal of four drugs used in monotherapy during the first 2 years of treatment for newly diagnosed patients with epilepsy: carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), and valproate (VPA). We adopted the cost-minimization model because, although no single trial compares all four drugs directly, the clinical trials comparing two or more of these drugs in newly diagnosed cases show no significant difference in efficacy between the drugs in terms of seizure frequency. Considered in the cost analyses were frequency of side effects, retention rates, medical consultations, inpatient and accident and emergency costs, laboratory investigations, and drug changes. A Delphi panel provided the treatment pathways, including frequency of clinical consultations, second-line monotherapy, and side-effects management. A sensitivity analysis was performed, varying the assumptions on which the calculations were based. Analysis was completed for a prospective, intention-to-treat perspective and also for those patients continuing the initial drug. The direct medical costs of 2-years therapy (intention-to-treat analysis) calculated for each trial were pound sterling 795-829 for CBZ, pound sterling 1,525-2,076 for LTG, pound sterling 736-768 for PHT, and pound sterling 868-884 for VPA. A sensitivity analysis provided similar relative estimates. We found that LTG for newly diagnosed patients is significantly more expensive in direct health service costs incurred. This analysis incorporated seizure control, side effects, and tolerability. We recommend that a similar type of analysis be considered as part of all clinical trials of antiepileptic drugs in which efficacy of outcome is similar as a guide to assess optimal cost effectiveness.

Epilepsy is an important health problem throughout the world. In order to best manage epilepsy within a population, its epidemiological profile should be established. Epidemiological studies have shown that epilepsy is a very common, chronic condition that particularly affects the young and those in developing countries. Although the reported rates vary widely, the annual incidence rate of epilepsy is estimated to be approximately 40 to 70 per 100 000 population, and the prevalence is estimated to be approximately 4 to 10 per 1000 population.

Objectives: To examine the influence of side of pathology and gender on changes in cognitive function across the adult lifespan in a homogenous sample of patients with mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS). Methods: We retrospectively examined the neuropsychological profiles of 382 patients in 3 cohorts: cohort 1 aged 18–30 (n = 171), cohort 2 aged 31–45 (n = 170), and cohort 3 aged 46–65 (n = 41). All participants had medically intractable seizures associated with unilateral HS and an onset of epilepsy in childhood, with an average onset at 7 years. Results: There were no significant differences between the age cohorts on the measures of intellect, language, or memory. Duration of epilepsy (years) was not related to IQ, memory, or language scores in any group. Male subjects performed better than female subjects on verbal IQ, performance IQ, and naming tasks. Verbal learning and recall scores were worse in those with left than right HS. Conclusions: Our findings suggest that the profile of cognitive deficits associated with MTLE is already established as children with temporal lobe epilepsy enter adulthood. While memory and language skills are maximally affected, intellectual function is also compromised in MTLE. This profile appears to remain stable across the adult lifespan, at least until 60 years of age, despite the intractable nature of the seizures. Side of pathology and gender are significant mediating factors in shaping the profile of cognitive deficits associated with childhood-onset MTLE, with people with left-sided HS and female subjects particularly vulnerable to more widespread cognitive dysfunction.

Introduction: Guidelines from the National Institute for Health and Clinical Excellence (NICE) and the International League Against Epilepsy recommend long term EEG monitoring (LTM) in patients for whom seizure or syndrome type is unclear, and in patients for whom it is proving difficult to differentiate between epilepsy and non-epileptic attack disorder (NEAD). The purpose of this study was to evaluate this recommended use of LTM in the setting of an epilepsy tertiary referral unit. Methods: This study reviewed the case notes of all admissions to the Sir William Gowers Unit at the National Society for Epilepsy in the years 2004 and 2005. A record was made of the type, duration and result of all LTM performed both prior to and during the admission. Pre- and post-admission diagnoses were compared, and patients were divided according to whether LTM had resulted in a change in diagnosis, refinement in diagnosis or no change in diagnosis. The distinction between change and a refinement in the diagnosis was made on the basis of whether or not this alteration resulted in a change in management. Results: 612 patients were admitted during 2004 and 2005, 230 of whom were referred for diagnostic clarification. Of these, LTM was primarily responsible for a change in diagnosis in 133 (58%) and a refinement of diagnosis in 29 (13%). In 65 (29%) patients the diagnosis remained the same after LTM. In those patients in whom there was a change in diagnosis, the most common change was in distinguishing epilepsy from NEAD in 73 (55%) and in distinguishing between focal and generalised epilepsy in 47 (35%). LTM was particularly helpful in differentiating frontal lobe seizures from generalised seizures and non-epileptic attacks. Inpatient ambulatory EEG proved as effective as video telemetry in helping to distinguish between NEAD, focal and generalised epilepsy. Discussion: The study revealed that LTM led to an alteration in the diagnosis of 71% of patients referred to a tertiary centre for diagnostic clarification of possible epilepsy. Although LTM is relatively expensive, time consuming and of limited availability, this needs to be balanced against the considerable financial and social cost of misdiagnosed and uncontrolled seizures. This service evaluation supports the use of performing LTM (either video or ambulatory) in a specialist setting in patients who present diagnostic difficulty.

Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for iatrogenic transmission of prion infection. Possible explanations include coincidental occurrence, common exposure to an unidentified environmental source of prions, horizontal transmission of disease, or the presence of unknown shared genetic predisposition.

Multiple sclerosis (MS) is the most common neurological cause of disability in young people. The disease-modifying treatments, IFN-beta and glatiramer acetate, have been widely available over the last decade and have shown a beneficial effect on relapse rate and magnetic resonance imaging parameters of disease activity; however, their effect on disease progression and disability is modest. Therefore, the search for alternative treatment strategies continues. As understanding of the heterogeneous pathophysiology of MS has increased, emphasis has shifted to more selective therapy that targets components of the inflammatory cascade and the promotion of remyelination and neuroprotection. These agents target the blood-brain barrier, systemic immune dysfunction, local inflammation and neurodegeneration. Combination therapies are being investigated for patients who fail first-line treatments. Many new drugs are being developed and tested that address these issues with the aim of finding a more effective and convenient therapy. These include humanized monoclonal antibodies such as daclizumab (IL-2 antagonist), oral immunomodulators such as sirolimus and statins and neuroprotective agents such as NMDA antagonists and Na+-channel blockers. Many of the treatments discussed in this review are still at early stages of development, but provide exciting potential treatment options; others have proved disappointing in larger extended-phase studies.

We read with interest the recent paper on network meta-analysis [1] in which efficacy and tolerability of selected anti-epileptic drugs in people with refractory focal epilepsy were compared. Whilst network meta-analysis may be a powerful tool, the validity of the results must depend on the selection of studies included. In this respect, we are curious about several methodological points. The authors include some studies but not others that are of the same nature. The authors deem as appropriate doses those that most experienced epilepsy clinicians would consider unusual and the results that emerge would be considered misleading by most experienced epilepsy clinicians. Only one of the four drugs the authors suggest have efficacy and tolerability in focal epilepsies would be accepted as such by experienced epilepsy clinicians. Their recommendation of vigabatrin in this category is most surprising, given the significant adverse effects associated with its use. The paper illustrates the importance of ensuring that the results of any complex statistical process should always be checked against actual clinical experience. The authors selected for comparison only people receiving doses of the target drugs which they deemed appropriate. Despite the authors’ claim that they chose the selected doses based on their clinical experience, the choice seems arbitrary, is out of keeping with clinical experience and is not based on any stated evidence. For instance, only someone with little clinical experience of oxcarbazepine would consider doses over 1800 mg day−1 as appropriate. The dose of 2400 mg is poorly tolerated by most people. It is also unlikely that many people would tolerate doses of topiramate over 300 mg day−1. Several relevant studies were not included, without clear explanation. For instance, a key lacosamide study [2] was not included. The same apply for studies with topiramate [3] and levetiracetam [4]. Two relevant lamotrigine studies [5, 6] were also excluded. One could suggest that these were excluded as they were crossover studies, but then other crossover studies were included, such as a levetiracetam study [7]. It is imperative that consistent criteria are applied for study selection if this type of analysis is to be meaningful. The authors conclude that in their mixed-treatment network meta-analysis, levetiracetam, vigabatrin, sodium valproate and gabapentin emerge as the anti-epileptic drugs with the best combination of short term efficacy and tolerability. As experienced epilepsy clinicians having seen many thousands of patients, we do not consider that valproate and gabapentin should be considered as first line anti-epileptic drugs for people with focal epilepsy, whilst any epilepsy clinician would know that the risk of visual field loss with vigabatrin is far too high to contemplate its regular use. The authors’ recommendation on valproate appears to emanate from one old study comparing vigabatrin with valproate, in which a small number of people with epilepsy not controlled by carbamazepine were given either valproate or vigabatrin [8]. It is not clear why better quality data [9] were omitted from the analysis. For these reasons, the conclusions cannot be considered particularly helpful. The need for answers to the questions the authors set out to address remains. One important thing to remember is that epilepsy, a symptom-complex, is not a single disease but a collection of many different conditions for which the current clinical trials paradigm is completely inappropriate [10, 11].

*School of Public Health, University of Texas-Houston, Houston, Texas, U.S.A.; †Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; ‡Epilepsy Research and Services, Chatswood, Australia; §Institute of Psychiatry, Kings College London, England; Department of Neurology, Comprehensive Epilepsy Program, University of Rochester Medical Center, Rochester, New York, U.S.A.; §§Swiss Epilepsy Centre, Zurich, Switzerland; **Department of Neurosurgery, University Hospital, Umea, Sweden; ††Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A; and ‡‡Department of Clinical Neurological Sciences, University Hospital, London, Ontario, Canada