Seizure Remission Rates Research Articles

A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: Seizure response, adverse events, and verbal memory

The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale-Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having "significant improvement," "no change," and "significant impairment" based on relative change indices. Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy.

Seizure Remission in Adults with Intractable Epilepsy: Not Just a Pipe Dream

Likelihood of Seizure Remission in an Adult Population with Refractory Epilepsy. Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Ann Neurol 2007;62(4):382–389. OBJECTIVE: We aimed to determine the likelihood of remission and its clinical predictors in adult patients meeting a strict definition of refractory epilepsy. We also wanted to investigate the influence of treatment regimen on remission. METHODS: A total of 246 patients with treatment refractory epilepsy (having at least 1 seizure per month and having not responded positively to at least 2 antiepileptic drugs) were identified in 2000 and followed for 3 years. We used Kaplan-Meier methods to estimate the rate of achieving a 6-month terminal seizure remission and Cox regression analysis to evaluate clinical predictors for seizure remission. RESULTS: The estimated 6-month terminal seizure remission rate was 19% (95% confidence interval, 14–26%) for all cases and 14% (95% confidence interval, 10–21%) when limited to those treated only with medication. Negative predictors for remission included a history of status epilepticus, younger age at intractability, number of failed drug therapies, and presence of mental retardation. No specific drug was significantly associated with remission, and frequently, no clear intervention led to terminal remission. INTERPRETATION: Fifteen percent (approximately 5% per year) of a drug refractory epilepsy population obtained a 6-month terminal seizure remission. Our results signify that no matter how many antiepileptic drug therapies have failed, there is always hope of a meaningful seizure remission in this population. Furthermore, we have elucidated four clinical predictors that can aid the epileptologist in prognostication.

Likelihood of seizure remission in an adult population with refractory epilepsy

We aimed to determine the likelihood of remission and its clinical predictors in adult patients meeting a strict definition of refractory epilepsy. We also wanted to investigate the influence of treatment regimen on remission. A total of 246 patients with treatment refractory epilepsy (having at least 1 seizure per month and having not responded positively to at least 2 antiepileptic drugs) were identified in 2000 and followed for 3 years. We used Kaplan-Meier methods to estimate the rate of achieving a 6-month terminal seizure remission and Cox regression analysis to evaluate clinical predictors for seizure remission. The estimated 6-month terminal seizure remission rate was 19% (95% confidence interval, 14-26%) for all cases and 14% (95% confidence interval, 10-21%) when limited to those treated only with medication. Negative predictors for remission included a history of status epilepticus, younger age at intractability, number of failed drug therapies, and presence of mental retardation. No specific drug was significantly associated with remission, and frequently, no clear intervention led to terminal remission. Fifteen percent (approximately 5% per year) of a drug refractory epilepsy population obtained a 6-month terminal seizure remission. Our results signify that no matter how many antiepileptic drug therapies have failed, there is always hope of a meaningful seizure remission in this population. Furthermore, we have elucidated four clinical predictors that can aid the epileptologist in prognostication.

Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy.

Epilepsy surgery can result in complete seizure remission rates of upto 80% in patients with mesial temporal sclerosis and unilateral seizures. The seizure-free rate after surgery for patients with extratemporal nonlesional epilepsy has ranged between 30% and 40%. Some patients with medically refractory localization-related epilepsy cannot be offered surgical resection because of inadequate localization of the epileptogenic zone, documentation of bilateral ictal onsets, or functionally important areas of cortex that prohibit resection. The short-term rate of complete remission with medications in temporal lobe epilepsy is poor. Less is known about remission rates in patients who are not surgical candidates. In this study, we evaluated the outcome of medical treatment in patients with medically refractory partial epilepsy who were evaluated for possible epilepsy surgery but deemed to be inadequate surgical candidates. A retrospective chart review and telephone survey with a self-rating questionnaire were completed for all patients who underwent epilepsy surgery evaluation but were not ultimately offered surgical treatment at the University of Michigan from 1990 through 1998. We assessed changes in seizure frequency and type, imaging characteristics, ictal recordings, interim medication history, and subjective changes in quality of life. Thirty-four subjects were available for follow-up study, at an average of >4 years after surgical evaluation. A significant reduction in seizure frequency was noted at the time of follow-up compared with that at the time of surgical evaluation. Of patients, 21% achieved seizure remission and remained seizure free for an average of 2.5 years. Four of the seven seizure-free patients attributed their remission to new antiepileptic drugs (AEDs). On a global self-rating item, 15 of 34, or 44%, felt more or much more satisfied with their lives, and 41% felt their quality of life was stable. A surprisingly large number of patients we surveyed, with refractory partial epilepsy not eligible for surgical management, reported reduced seizure frequency at follow-up, and 21% were seizure free. Our findings suggest that the long-term prognosis in patients with refractory partial epilepsy who are not surgical candidates may be more positive than might be generally expected.

Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex.

Epilepsy is a common neurologic complication of tuberous sclerosis complex (TSC) and it is often refractory to treatment. Therefore, treating physicians are often reluctant to discontinue antiepileptic drugs (AEDs) in individuals with TSC who have attained seizure remission. To our knowledge, seizure remission and AED discontinuation in children with TSC has not been studied. To characterize seizure remission and AED discontinuation in children with TSC. Retrospective medical record and neuroimaging analysis of 15 children with TSC and epilepsy who had seizure remission, with a subsequent trial of discontinuation of AED treatment. The seizure remission rate for the group of patients with TSC and epilepsy was 14.2%. From the group of 15 patients who had a remission, the absolute relapse rate was 26.7% after a mean follow-up of 5 years 7 months. Patients with sustained remission were more likely to have normal intelligence and only a few cortical or subcortical lesions on neuroimaging. The proportion of children with TSC and epilepsy who achieve seizure remission is small. Nevertheless, some do attain seizure remission, and AEDs may be successfully discontinued. Mild cerebral involvement is a general clinical marker for seizure remission. The relapse rate in those who have undergone a trial of discontinuation of AED therapy is comparable with the rate in the general pediatric population with epilepsy.

A study of mortality after temporal lobe epilepsy surgery.

To determine early and late mortality in a cohort of 305 consecutive patients who had temporal lobe epilepsy (TLE) surgery over a 20-year period. Survival status, cause of death, and postoperative clinical details of those who died were ascertained in a cohort of 305 patients who had TLE surgery. Mortality was related to postoperative seizure status, operative pathology, and side of resection. The survival status of 299 patients was established. Twenty deaths occurred. Mortality was 1 per 136 person-years, with a standardized mortality ratio (SMR) of 4.5 (95% confidence interval [CI], 3.2 to 6.6). Six deaths were sudden and unexpected (SUDEP). The SUDEP rate was 1 per 455 person-years. The overall death and SUDEP rates were lower than those reported for similar patient populations with chronic epilepsy. Mortality in patients who had right-sided resections for mesial temporal sclerosis (MTS) remained considerably elevated with a mortality rate of 1 per 54 person-years, an SMR of 32.0 (95% CI, 24.7 to 40.5), and a SUDEP rate of 1 per 134 person-years. These patients had significantly lower seizure remission rates than left-sided patients, but the excess mortality was not simply explained by those patients whose partial seizures were uninfluenced by surgery. Patients who died had more severe or convulsive seizures despite an overall reduction in seizure frequency. The present findings confirm previous reports that TLE surgery lowers but does not normalize the overall mortality associated with chronic epilepsy. In patients with right-sided MTS, however, the postoperative mortality has remained similar to other groups with medically intractable seizures.

Innovative monotherapy trial designs for the assessment of antiepileptic drugs: a critical appraisal.

Although new antiepileptic drugs are assessed initially by adding them to pre-existing treatment, it is only through monotherapy studies that their therapeutic potential can be characterized in full. Since long-term treatment with a placebo alone is ethically unacceptable in epilepsy, the classical monotherapy assessment of antiepileptic drugs involves randomization of newly diagnosed patients to treatment with the investigational drug or an established active control, followed by long-term monitoring to determine seizure remission rates and potential adverse effects. These protocols, however, are time-consuming and they are unlikely to demonstrate a superior efficacy of the new agent over a comparator. In turn, a "no-difference" outcome in terms of seizure control does not allow one to exclude the possibility that all the treatments were equally ineffective, and may therefore not be regarded as proof of efficacy by regulatory authorities. To circumvent these problems, innovative designs for the early monotherapy evaluation of new antiepileptic drugs have been developed in recent years. These protocols, often referred to as "regulatory trials", involve short-term studies in which a full dosage of the investigational agent is compared with a placebo or with a suboptimal dosage of an active control (possibly the investigational agent itself). To minimize the risks associated with an ineffective treatment, provisions are made that require exit from the trial if seizures are inadequately controlled. Efficacy endpoints are time to the n(th) seizure and patients' retention on the allocated treatment. These studies have been conducted in patients undergoing discontinuation of treatment for presurgical assessment, in newly diagnosed patients, and in patients whose concomitant anticonvulsants were withdrawn for trial purposes. While these trials allow statistical demonstration of superior efficacy over a comparator, allocation of patients to ineffective or suboptimal treatments raises serious ethical concerns. The scientific value of these studies is also doubtful, because dosing schedules and duration of treatment are hardly relevant to routine clinical practice. Clinicians do not need to know whether a new drug given for a few days is better than nothing, but how that drug compares with established agents given in optimized dosages for long periods of time. The ethical and scientific justification for regulatory trials should be reassessed, and steps are urgently needed to stimulate implementation of long-term randomized comparative trials under conditions that are more relevant to clinical needs.

National General Practice Study of Epilepsy (NGPSE): partial seizure patterns in a general population.

The National General Practice Study of Epilepsy (NGPSE) is a prospective community-based study of newly diagnosed epileptic seizures. Of 594 patients with definite epileptic seizures, 160 (26.9%) had seizures with a clinically localizable onset: 36 (22.5%) frontal, 52 (32.5%) central sensorimotor, 43 (27%) temporal, nine (5.6%) frontotemporal, and 10 each (6.3%) parietal and other posterior cortex. There was no difference among these groups in seizure frequency or remission rate; 46.5% were seizure free and 6.9% had severe epilepsy. Etiology was identifiable in 41% and focal CT and EEG abnormalities in 33% and 19%, with results discordant with the clinical seizure localization in 21% and 20%. Temporal lobe epilepsy may be underreported, as it may be more difficult to localize clinically. Extratemporal seizures are extremely common in the general population, especially frontal and central sensorimotor, in relation to cerebrovascular disease. Prognoses are similar for partial epilepsies with different clinical patterns and regions of onset and are much better than suggested in hospital-based studies. The clinical, EEG, and CT localizations may frequently be discordant in this nonrefractory group.