Acta Neurol Scand 2015: 131: 58–62 DOI: 10.1111/ane.12311
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
The prognosis of refractory epilepsy patients rejected from epilepsy surgery Gonen OM, Gandelman-Marton R, Kipervasser S, Neufeld MY. The prognosis of refractory epilepsy patients rejected from epilepsy surgery. Acta Neurol Scand 2015: 131: 58–62. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. Methods – The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. Results – Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. Conclusions – A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.
Introduction
In spite of adequate treatment with two or more anti-epileptic drugs (AEDs), about one-third of individuals diagnosed as having epilepsy are not seizure-free and considered as being refractory to medical treatment (1–4). The chance of subsequent freedom from seizures with further drug adjustments in those patients is around 5–25% per year (5). They are often referred for evaluation to consider their suitability for resective epilepsy surgery (2). Vagus nerve stimulator (VNS) implantation is a viable treatment option for those who are not surgical candidates (6). Little is known about the group of patients who had 58
O. M. Gonen1, R. GandelmanMarton2,3, S. Kipervasser3, 4, M. Y. Neufeld3, 4 1 Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel; 2Epilepsy and EEG Unit, Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel; 3Sackler School of Medicine, TelAviv University, Tel-Aviv, Israel; 4Epilepsy and EEG Unit, Department of Neurology, Tel-Aviv Medical Center, Tel-Aviv, Israel
Key words: epilepsy surgery; prognosis; refractory epilepsy; vagus nerve stimulation O. M. Gonen, The Neurology Department, Assaf Harofeh Medical Center, Zerifin, 70300 Israel Tel.: +972-8-9779181 Fax: +972-8-9779183 e-mail: [email protected] Accepted for publication August 27, 2014
been rejected from epilepsy surgery, and there are few reports describing their long-term outcome (7–10). Most of the patients described as being rejected from surgery in the above-cited studies had been evaluated more than a decade ago: ~5– 20% of them reported that they had become seizure-free, and up to 76% reported a reduction in seizure frequency over time (8). We assumed that new AEDs and refined VNS techniques might have contributed to an improvement in seizure control. The aim of our study was to compare the outcome and clinical characteristics of patients, who had been rejected from or chose not to undergo epilepsy surgery following evaluation for their
Prognosis of refractory epilepsy suitability for surgery in the Epilepsy Unit at the Tel-Aviv Sourasky Medical center (TASMC) and were either treated with AEDs only or also underwent VNS implantation. Methods
The study was approved by the TASMC Institutional Review Board. The medical records of adult patients (>18 years of age) who were referred for presurgical evaluation and subsequently deemed to be inappropriate candidates for resective epilepsy surgery between 2007 and 2011 were reviewed. Inclusion criteria for consideration of epilepsy surgery, and hence for the study, included suffering from pharmacoresistant seizures with a deleterious effect on the quality of life, as reported by the patients. Pharmacoresistance was defined as the failure to achieve seizure control despite the trial of at least two appropriate AEDs with adequate dosage. Patients who were referred for VNS implantation were, in addition, patients who were deemed not suitable for resective surgery, or who elected to undergo a less invasive procedure. All of these patients either continued medical therapy only or underwent VNS implantation in addition to the medical treatment and had at least 1 year of follow-up after the video-EEG monitoring they had undergone as part of their presurgical evaluation. Exclusion criteria included prior epilepsy surgery and refusal to participate in the telephone interview. In cases of mentally retarded individuals, refusal of the family or legal guardian was considered a reason for exclusion from the study. Data on demographic characteristics, medical history, results of video-EEG monitoring, imaging studies, and neuropsychological evaluations were collected from the medical records in the departmental database. Baseline information on seizure frequency and use of AEDs was based on the information collected from the records at admission to the video-EEG monitoring unit. If no such information was available, baseline information for the VNS-implanted group was taken on the date of the implantation procedure, and regarded as ‘missing’ in the medically treated group. The patients or their first-degree adult relatives or legal guardians were contacted by telephone. After giving verbal informed consent, they were questioned about current AEDs and seizure frequency during the previous 3 months. Seizure frequency was scored from 1 to 4: 0 = seizure-free (no seizures during the previous 3 months); 1 = ≥1 seizures during the last 3 months, but not within the past month; 2 = ≥1
seizures per month; 3 = ≥1 seizures per week; and 4 = ≥1 seizures per day. Statistics
The statistical analysis was performed with IBM SPSS version 21.0 (SPSS Inc., Chicago, IL, USA). Mean differences between demographic characteristics of the two groups were calculated using Student’s t-test for continuous variables and chisquare test or Fisher’s exact test for categorical data. The Wilcoxon signed-rank test was used to compare the data on seizure frequency and medication use within each group between the evaluation period and the follow-up telephone interview. The Mann–Whitney U-test was used for nonparametric evaluations of the mean differences between the groups regarding seizure frequency and drug treatment at both time points. The level of significance was set to a = 0.05 (two sided). Results
Eighty-seven patients were initially included in the analysis: 52 were treated with AEDs only, and 35 were treated with combined AEDs and VNS. Forty-seven of the medically treated patients and 33 of the VNS-implanted patients agreed to be interviewed by telephone. The 7 non-participants either could not be reached by telephone or language difficulties precluded holding the interview. The study patients’ demographic and clinical data and the reasons for rejection from surgery are presented in Table 1. In the VNS-implanted group 39.4% of the patients were mentally retarded, in comparison with 10.6% of the AEDs only group (P = 0.005). Fewer patients from the VNS group worked or studied independently (55.3% at baseline; 46.8% at follow-up) in comparison with the AEDs only group (29.0% at baseline; 30.3% at follow-up; P = 0.014 and P = 0.005, respectively). There was a statistically significant difference between the groups with regard to the reason for not undergoing resective surgery, leading to an overall P-value
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
The prognosis of refractory epilepsy patients rejected from epilepsy surgery Gonen OM, Gandelman-Marton R, Kipervasser S, Neufeld MY. The prognosis of refractory epilepsy patients rejected from epilepsy surgery. Acta Neurol Scand 2015: 131: 58–62. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. Methods – The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. Results – Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. Conclusions – A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.
Introduction
In spite of adequate treatment with two or more anti-epileptic drugs (AEDs), about one-third of individuals diagnosed as having epilepsy are not seizure-free and considered as being refractory to medical treatment (1–4). The chance of subsequent freedom from seizures with further drug adjustments in those patients is around 5–25% per year (5). They are often referred for evaluation to consider their suitability for resective epilepsy surgery (2). Vagus nerve stimulator (VNS) implantation is a viable treatment option for those who are not surgical candidates (6). Little is known about the group of patients who had 58
O. M. Gonen1, R. GandelmanMarton2,3, S. Kipervasser3, 4, M. Y. Neufeld3, 4 1 Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel; 2Epilepsy and EEG Unit, Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel; 3Sackler School of Medicine, TelAviv University, Tel-Aviv, Israel; 4Epilepsy and EEG Unit, Department of Neurology, Tel-Aviv Medical Center, Tel-Aviv, Israel
Key words: epilepsy surgery; prognosis; refractory epilepsy; vagus nerve stimulation O. M. Gonen, The Neurology Department, Assaf Harofeh Medical Center, Zerifin, 70300 Israel Tel.: +972-8-9779181 Fax: +972-8-9779183 e-mail: [email protected] Accepted for publication August 27, 2014
been rejected from epilepsy surgery, and there are few reports describing their long-term outcome (7–10). Most of the patients described as being rejected from surgery in the above-cited studies had been evaluated more than a decade ago: ~5– 20% of them reported that they had become seizure-free, and up to 76% reported a reduction in seizure frequency over time (8). We assumed that new AEDs and refined VNS techniques might have contributed to an improvement in seizure control. The aim of our study was to compare the outcome and clinical characteristics of patients, who had been rejected from or chose not to undergo epilepsy surgery following evaluation for their
Prognosis of refractory epilepsy suitability for surgery in the Epilepsy Unit at the Tel-Aviv Sourasky Medical center (TASMC) and were either treated with AEDs only or also underwent VNS implantation. Methods
The study was approved by the TASMC Institutional Review Board. The medical records of adult patients (>18 years of age) who were referred for presurgical evaluation and subsequently deemed to be inappropriate candidates for resective epilepsy surgery between 2007 and 2011 were reviewed. Inclusion criteria for consideration of epilepsy surgery, and hence for the study, included suffering from pharmacoresistant seizures with a deleterious effect on the quality of life, as reported by the patients. Pharmacoresistance was defined as the failure to achieve seizure control despite the trial of at least two appropriate AEDs with adequate dosage. Patients who were referred for VNS implantation were, in addition, patients who were deemed not suitable for resective surgery, or who elected to undergo a less invasive procedure. All of these patients either continued medical therapy only or underwent VNS implantation in addition to the medical treatment and had at least 1 year of follow-up after the video-EEG monitoring they had undergone as part of their presurgical evaluation. Exclusion criteria included prior epilepsy surgery and refusal to participate in the telephone interview. In cases of mentally retarded individuals, refusal of the family or legal guardian was considered a reason for exclusion from the study. Data on demographic characteristics, medical history, results of video-EEG monitoring, imaging studies, and neuropsychological evaluations were collected from the medical records in the departmental database. Baseline information on seizure frequency and use of AEDs was based on the information collected from the records at admission to the video-EEG monitoring unit. If no such information was available, baseline information for the VNS-implanted group was taken on the date of the implantation procedure, and regarded as ‘missing’ in the medically treated group. The patients or their first-degree adult relatives or legal guardians were contacted by telephone. After giving verbal informed consent, they were questioned about current AEDs and seizure frequency during the previous 3 months. Seizure frequency was scored from 1 to 4: 0 = seizure-free (no seizures during the previous 3 months); 1 = ≥1 seizures during the last 3 months, but not within the past month; 2 = ≥1
seizures per month; 3 = ≥1 seizures per week; and 4 = ≥1 seizures per day. Statistics
The statistical analysis was performed with IBM SPSS version 21.0 (SPSS Inc., Chicago, IL, USA). Mean differences between demographic characteristics of the two groups were calculated using Student’s t-test for continuous variables and chisquare test or Fisher’s exact test for categorical data. The Wilcoxon signed-rank test was used to compare the data on seizure frequency and medication use within each group between the evaluation period and the follow-up telephone interview. The Mann–Whitney U-test was used for nonparametric evaluations of the mean differences between the groups regarding seizure frequency and drug treatment at both time points. The level of significance was set to a = 0.05 (two sided). Results
Eighty-seven patients were initially included in the analysis: 52 were treated with AEDs only, and 35 were treated with combined AEDs and VNS. Forty-seven of the medically treated patients and 33 of the VNS-implanted patients agreed to be interviewed by telephone. The 7 non-participants either could not be reached by telephone or language difficulties precluded holding the interview. The study patients’ demographic and clinical data and the reasons for rejection from surgery are presented in Table 1. In the VNS-implanted group 39.4% of the patients were mentally retarded, in comparison with 10.6% of the AEDs only group (P = 0.005). Fewer patients from the VNS group worked or studied independently (55.3% at baseline; 46.8% at follow-up) in comparison with the AEDs only group (29.0% at baseline; 30.3% at follow-up; P = 0.014 and P = 0.005, respectively). There was a statistically significant difference between the groups with regard to the reason for not undergoing resective surgery, leading to an overall P-value
