Gail S. Bell

The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study

BACKGROUND Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery. METHODS We report long-term outcome of surgery for epilepsy in 615 adults (497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and seven palliative procedures [corpus callosotomy, subpial transection]), with prospective annual follow-up for a median of 8 years (range 1-19). We used Kaplan-Meier survival analysis to estimate time to first seizure, and investigated patterns of seizure outcome. FINDINGS We used survival methods to estimate that 52% (95% CI 48-56) of patients remained seizure free (apart from simple partial seizures [SPS]) at 5 years after surgery, and 47% (42-51) at 10 years. Patients who had extratemporal resections were more likely to have seizure recurrence than were those who had anterior temporal resections (hazard ratio [HR] 2·0, 1·1-3·6; p=0·02); whereas for those having lesionectomies, no difference from anterior lobe resection was recorded. Those with SPS in the first 2 years after temporal lobe surgery had a greater chance of subsequent seizures with impaired awareness than did those with no SPS (2·4, 1·5-3·9). Relapse was less likely the longer a person was seizure free and, conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. 104 of 365 (28%) seizure-free individuals had discontinued drugs at latest follow-up. INTERPRETATION Neurosurgical treatment is appealing for selected people with refractory focal epilepsy. Our data provide realistic expectations and indicate the scope for further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy. FUNDING UK Department of Health National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme, Epilepsy Society, Dr Marvin Weil Epilepsy Research Fund.

ArticlesThe long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study

BACKGROUND Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery. METHODS We report long-term outcome of surgery for epilepsy in 615 adults (497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and seven palliative procedures [corpus callosotomy, subpial transection]), with prospective annual follow-up for a median of 8 years (range 1-19). We used Kaplan-Meier survival analysis to estimate time to first seizure, and investigated patterns of seizure outcome. FINDINGS We used survival methods to estimate that 52% (95% CI 48-56) of patients remained seizure free (apart from simple partial seizures [SPS]) at 5 years after surgery, and 47% (42-51) at 10 years. Patients who had extratemporal resections were more likely to have seizure recurrence than were those who had anterior temporal resections (hazard ratio [HR] 2·0, 1·1-3·6; p=0·02); whereas for those having lesionectomies, no difference from anterior lobe resection was recorded. Those with SPS in the first 2 years after temporal lobe surgery had a greater chance of subsequent seizures with impaired awareness than did those with no SPS (2·4, 1·5-3·9). Relapse was less likely the longer a person was seizure free and, conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. 104 of 365 (28%) seizure-free individuals had discontinued drugs at latest follow-up. INTERPRETATION Neurosurgical treatment is appealing for selected people with refractory focal epilepsy. Our data provide realistic expectations and indicate the scope for further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy. FUNDING UK Department of Health National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme, Epilepsy Society, Dr Marvin Weil Epilepsy Research Fund.

Progressive neocortical damage in epilepsy

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow‐up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions. Ann Neurol 2003

The long-term risk of premature mortality in people with epilepsy

People with epilepsy have an increased risk of premature death. The risk is highest soon after onset of seizures. We report the findings of a long-term follow-up population-based study of people with epilepsy with regards to premature mortality. The National General Practice Study of Epilepsy is a prospective study flagged at the National Health Service Information Centre in the UK. Over 1000 people with new onset seizures were followed from the mid 1980s until April 2009. Of these, 564 people were classified at 6 months as having definite epileptic seizures, 228 as having possible epileptic seizures and 220 as having febrile seizures. The remainder were excluded (n=104 because of an unknown prior diagnosis of epilepsy or neonatal seizures) or classified as not having epilepsy (n=79). At median follow-up of 22.8 years there had been 301 deaths in the cohort; 300 of these were in people with definite or possible seizures. Death certificates were obtained for all but three of those who died. The overall standardized mortality ratio for those with definite or possible epilepsy was 2.2 (95% confidence interval 1.97-2.47), and was higher in those with definite seizures (2.6). In those who were alive at 20 years follow-up, the standardized mortality ratio in the subsequent years remained significantly elevated (2.2, 95% confidence interval 1.6-3.2). Pneumonia (standardized mortality ratio 6.6, 95% confidence incidence 5.1, 8.4) was a common cause of death with a consistently elevated standardized mortality ratio throughout follow-up. The standardized mortality ratio for ischaemic heart disease was significantly elevated for the first time in the last 5 years of follow-up (3.3, 95% confidence interval 1.6-7.0). Few people died from epilepsy-related causes. The risk of premature death remains significantly elevated at 20-25 years after the index seizure despite most of the cohort being in terminal remission (defined as 5 years or more seizure-free, on or off anti-epileptic medication) at the last follow-up. Further studies are needed to explore the reasons for this long-term increase in premature mortality.

A longitudinal study of brain morphometrics using quantitative magnetic resonance imaging and difference image analysis

Serial quantitative magnetic resonance imaging (MRI) allows the detection of subtle volumetric changes in brain volume. We used serial volumetry and voxel-based difference image analysis to quantify and characterize longitudinal changes in the hippocampus, cerebellum, and neocortex in younger and middle-age individuals. Paired volumetric MRI brain scans 3.5 years apart were performed on 90 healthy subjects 14 to 77 years old. Quantitative assessment of registered images included hippocampal volumetry, cerebellar volumetry, and automatically determined regional brain volumes. Longitudinal volume changes in three age epochs (<35, 35-54, >54 years) were compared and neocortical changes beyond regions of interest were visualized using filtered difference images. Cross-sectional analysis revealed a significant association between age and reduction in all brain volumes except hippocampal volume. Changes in normalized hippocampal and white matter volume were significantly different among the three groups. Individual analysis revealed 5 subjects with significant longitudinal volume changes lying outside the normative range. Difference image analysis showed global involutional changes in the >54 age group. Our findings suggest that cross-sectional observations in intracranial volume, cerebellar volume, and gray matter volume are likely to reflect uniform rates of volume loss or secular changes. Accelerated brain atrophy was seen from the age of 35-54 and increased rates of hippocampal atrophy from the age of 54. Our findings emphasize the importance of controlling for age effects when studying pathological brain changes over a wide age range.

CPD - Education and self-assessment. The epidemiology of epilepsy: The size of the problem

The prevalence of epilepsy is generally taken as between 5 and 10 cases per 1000 persons, and the overall incidence as about 50 cases per 100,000 persons. The rates are dependent on case ascertainment and on definitions used. The prognosis depends on many factors, including the number of seizures at presentation, the seizure type and the use of anti-epileptic drugs. Epilepsy carries an excess mortality; the cause of death can be unrelated to epilepsy, related to the underlying disease causing epilepsy, or related to epilepsy itself.

Omega-3 fatty acid supplementation in patients with chronic epilepsy: A randomized trial

Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.7 g docosahexaenoic acid (DHA) daily, 57 patients completed a 12-week double-blind phase. Seizure frequency was reduced over the first 6 weeks of treatment in the supplement group, but this effect was not sustained. The supplementation produced a significant increase in EPA and DHA concentrations and a reciprocal fall in arachidonic and linoleic acid concentrations. No change in serum AED concentrations was detected. Further studies are required to examine different omega-3 FA preparations, different doses, longer treatment duration, and larger sample sizes.

Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: A case-control study

Purpose:  To determine whether abnormal cardiac repolarization and other electrocardiography (ECG) predictors for cardiac mortality occur in epilepsy patients and whether they are associated with an increased risk for sudden unexpected death in epilepsy (SUDEP).

Suicide in people with epilepsy: How great is the risk?

Purpose:  Suicide is more common in populations with epilepsy, but estimates vary concerning the magnitude of the risk. We aimed to estimate the risk using meta‐analysis.

Prevalence and Pattern of Epilepsy Treatment in Different Socioeconomic Classes in Brazil

Summary:  Purpose: The worldwide prevalence of epilepsy is variable, estimated at 10//1,000 people, and access to treatment is also variable. Many people go untreated, particularly in resource‐poor countries.