this study provides class iii evidence that more patients are seizure - free and have stopped aed treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients . in sweden , all epilepsy surgery procedures are reported to the snesur , which was initiated in 1990 . an internal control system rejects certain impossible combinations of data and regular external quality controls are performed by an independent controller . since 2005 , the follow - up has been extended from 2 years to 5 , 10 , and 15 years postoperatively . snesur contains baseline information on patient 's epilepsy history , preoperative seizure types and syndromes , mean monthly seizure frequency during the year preceding the presurgical investigation , aeds , preoperative investigations , psychosocial data , surgical data ( type and location of surgery ) , histopathologic diagnoses , and postoperative complications . two - year follow - up data cover seizure situation , aeds , and psychosocial data . the 5- , 10- , and 15-year follow - ups are structured telephone interviews regarding seizure situation , aeds , psychosocial aspects , and driving . in this study , we analyzed seizure outcome and aed medication 5 and 10 years after resective epilepsy surgery in patients who had 5- and 10-year follow - ups in 2005 to 2007 ( and hence were operated on in 2000 to 2002 and 1995 to 1997 ) . the cohort comprises the 327 patients who had resective surgery during these time periods . in 2005 to 2007 , 144/176 patients operated on in 1995 to 1997 ( 98/116 adults and 46/60 children 18 years ) had a 10-year follow - up , and 134/151 patients operated on in 2000 to 2002 ( 92/103 adults and 42/48 children 18 years ) had a 5-year follow - up . seventeen patients were reoperated before long - term follow - up and there were 11 deaths . twenty - one patients ( 6.4% ) were lost to follow - up ( for details , see figure e-1 on the neurology web site at www.neurology.org ) . as a control group , consecutive patients who underwent presurgical investigations during the same time periods but were not operated were identified at 3 of the 6 operating centers ( gteborg , uppsala , and lund ) . eighty adults and 13 children out of 94 adults and 13 children underwent a cross - sectional long - term follow - up in 2008 after a mean of 9.3 years ( adults ) and 8.8 years ( children ) using the same structured telephone interview as for the surgical group . thirteen adult patients had died ( 4 epilepsy - related deaths ) and 1 was lost to follow - up ( 1% ) . reasons for not having surgery were nonconclusive workup ( n = 41 ) , multifocality ( n = 27 ) , patient declined surgery ( n = 12 ) , seizure onset within eloquent cortex ( n = 11 ) , and neuropsychological reasons ( n = 2 ) . seizure freedom ( without or with aura , international league against epilepsy [ ilae ] class i and ii ) is reported for the year preceding the follow - up except for patients with sustained seizure freedom since surgery , which is separately reported . for patients with continuing seizures or seizure relapse postoperatively , the mean monthly seizure frequency in the last year of follow - up is categorized as follows : 75% reduction in seizure frequency ; 50%74% reduction in seizure frequency ; 0%49% reduction in seizure frequency ; and increased seizure frequency . for comparison between 2 groups , fisher exact test was used for dichotomous variables , mann - whitney u test for continuous variables , and mantel - haenszel  test for ordered categorical variables . logistic regression analysis was performed for each independent variable to predict seizure - free outcome . a forward stepwise multiple logistic regression was used to select independent predictors to outcome . only univariate predictors attaining a p value of < 0.10 this study was approved by the regional board of medical ethics at the university of gothenburg . consent for research was obtained from all controls . for operated patients , the board considered long - term follow - up as a quality control measure not necessitating individual consent . primary research questions were as follows : are more patients seizure - free and without aed in the long term after resective epilepsy surgery compared to nonoperated patients ? this longitudinal observational study provides class iii evidence that 41% of adults and 44% of children have sustained seizure freedom in the long term after surgery compared to none of the nonoperated patients ( p < 0.0005 ) . also , 43% of seizure - free adults and 86% of seizure - free children had stopped aeds after 10 years compared to none of the nonoperated patients ( p < 0.0005 ) . this study was approved by the regional board of medical ethics at the university of gothenburg . consent for research was obtained from all controls . for operated patients , the board considered long - term follow - up as a quality control measure not necessitating individual consent . primary research questions were as follows : are more patients seizure - free and without aed in the long term after resective epilepsy surgery compared to nonoperated patients ? this longitudinal observational study provides class iii evidence that 41% of adults and 44% of children have sustained seizure freedom in the long term after surgery compared to none of the nonoperated patients ( p < 0.0005 ) . also , 43% of seizure - free adults and 86% of seizure - free children had stopped aeds after 10 years compared to none of the nonoperated patients ( p < 0.0005 ) . table 1 shows baseline characteristics of the operated patients and the controls , children ( 18 years ) and adults . the only adult who underwent hemispherectomy at age 20 was added to the pediatric hemispherectomy group . none of the baseline characteristics differed between operated and nonoperated patients , except for number of previously tried aeds in adults ( p < 0.001 ) and iq in children ( p = 0.042 ) . baseline data of operated patients and nonoperated controls there was no significant difference in seizure outcome between the operated patients who had follow - up after 5 years compared to 10 years . in order to enable comparison with the nonoperated group , who had a mean long - term follow - up of 9.1 years ( range 514 ) , the results from 5- and 10-year follow - ups in the operated patients were merged ( figure 1 ) . two - year and long - term ( mean follow - up time 7.6 years , range 510 ) seizure situation for patients after resective epilepsy surgery compared to long - term follow - up of nonoperated controls ( mean follow - up time 9.2 years , range 514 ) . seizure - free patients include those with sustained seizure freedom with or without aura since surgery ( blue ) and patients seizure - free at least the last year before follow - up ( green ) . overall , 117 ( 62% ) of the operated adults were seizure - free at long - term follow - up compared to 11 ( 14% ) of the controls ( p < 0.001 ) . fifty percent ( n = 93 ) of the operated adults had sustained seizure freedom at the 2-year and 41% ( n = 78 ) at the long - term follow - up . none of the controls was seizure - free for the whole time period . for the children , 44 ( 50% ) in the operated group were seizure - free the year before long - term follow - up , compared to 5 ( 38% ) in the control group ( not significant ) . fifty - three percent ( n = 46 ) of the operated children had sustained seizure freedom since surgery at the 2-year and 44% ( n = 39 ) at the long - term follow - up , compared to none in the control group . for both adults and children , the proportion with sustained seizure freedom at long term was significantly higher compared to the nonoperated patients ( p < 0.0005 ) . details on seizure outcome for the operated patients at 2 , 5 , and 10 years after epilepsy surgery are shown in table e-1 . eighty - seven percent of the adults as well as of the children who were seizure - free after 2 years were seizure - free at the 5- or 10-year follow - ups ( 95% confidence interval [ ci ] 7794 and 8095 , respectively ) . seizure outcomes for adults and children after different resection types are illustrated in table 2 . the most common resection type was tlr ( 81% in adults , 43% in children ) followed by frontal lobe resection ( flr ) in adults ( 12% ) and multilobe resection in children ( 20% ) . in adults , the best long - term seizure outcome was after tlr ( 63% seizure - free , sustained seizure freedom since surgery in 44% ) . in children the tlr outcome ( 60% seizure - free , 55% with sustained seizure freedom ) was matched by the long - term hemispherectomy results ( 60% seizure - free , all with sustained seizure freedom ) . if the extratemporal procedures are summed up , 31% of adults had sustained seizure freedom at long - term follow - up , compared to 36% of the children . seizure outcomes in the long term related to resection type the main histopathologic diagnoses were categorized as follows : hippocampal sclerosis ( hs , n = 45 ) , neurodevelopmental tumors ( n = 34 ) , low - grade astrocytomas ( n = 21 ) , cavernous hemangiomas ( n = 21 ) , malformations of cortical development ( n = 52 ) , gliosis ( n = 65 ) , and other ( n = 40 ) . highest seizure freedom rates were seen in hs ( 60% , 47% sustained since surgery ) and epileptogenic lesions ( 72% , 57% sustained since surgery ) ( table e-2 ) . the univariate relationship between long - term seizure freedom and the following baseline variables was explored for both operated patients and controls : epilepsy duration in percent of life length ( relative epilepsy duration , in odds ratio [ or ] increment units of 10% ) , 30 seizures / month , and presence of secondarily generalized tonic - clonic seizures ( sgtcs ) . for the operated patients , additional variables were positive mri , resection types , and histopathology ( figure 2 ) . for the controls , the univariate associations were nonsignificant although in the same direction as for the operated patients ( relative epilepsy duration , or 0.89 [ 95% ci 0.731.09 ] , 30 seizures / month , or 0.88 [ 95% ci 0.223.47 ] , and sgtcs , or 0.56 [ 95% ci 0.181.68 ] ) . in the surgical group , multivariate analysis was performed , where 30 seizures / month , or 0.40 ( 95% ci 0.230.69 ) , and relative epilepsy duration , or 0.91 ( 95% ci 0.831.00 ) , were negative predictors , while positive mri , or 1.96 ( 95% ci 1.083.55 ) , was a positive predictor of seizure - free long - term outcome . the auc value ( goodness of fit ) for the final multiple model was 0.66 . for the categorical variables with more than 2 categories ( resection type and histopathology ) , temporal lobe resections ( tlr ) and epileptogenic lesions ( epi les ) were chosen as reference categories . ci = confidence interval ; epi dur ( per 10% of life ) = epilepsy duration in percentage of life length , odds ratio units per 10% of life ; epileptogenic lesions = gangliogliomas , dysembryoplastic neuroepithelial tumors , cavernomas , and low - grade astrocytomas ; flr = frontal lobe resection ; he = hemispherectomy ; hs = hippocampal sclerosis ; mcd = malformations of cortical development ; mlr = multilobe resection ; or = odds ratio ; other = vascular malformations other than cavernomas , cysts , tuberous sclerosis , unknown histopathology ; p / olr = parietal or occipital lobe resection ; sgtcs = secondarily generalized tonic - clonic seizures . at baseline , 183 ( 66% ) of the patients had 2 aeds , 85 ( 31% ) had 1 aed , and 8 ( 3% ) had no aeds . the number of aeds used by the operated seizure - free patients decreased over time ( figure 3 ) . overall , 45 ( 54% ) patients who were seizure - free at 10-year follow - up had stopped aeds , compared to none of the seizure - free controls ( p < 0.0005 ) . more children than adults had stopped aeds ( 86% of the children and 43% of the adults , p = 0.002 ) . there was no significant association between the proportion of seizure - free patients who stopped aeds and resection type . among patients with seizures , the proportion with 2 aeds had increased from 77% preoperatively to 82% 10 years after surgery . number of antiepileptic drugs at the start of preoperative investigations , and after 2 , 5 , and 10 years for patients who were seizure - free at 5- or 10-year follow - up . table 1 shows baseline characteristics of the operated patients and the controls , children ( 18 years ) and adults . the only adult who underwent hemispherectomy at age 20 was added to the pediatric hemispherectomy group . none of the baseline characteristics differed between operated and nonoperated patients , except for number of previously tried aeds in adults ( p < 0.001 ) and iq in children ( p = 0.042 ) . there was no significant difference in seizure outcome between the operated patients who had follow - up after 5 years compared to 10 years . in order to enable comparison with the nonoperated group , who had a mean long - term follow - up of 9.1 years ( range 514 ) , the results from 5- and 10-year follow - ups in the operated patients were merged ( figure 1 ) . two - year and long - term ( mean follow - up time 7.6 years , range 510 ) seizure situation for patients after resective epilepsy surgery compared to long - term follow - up of nonoperated controls ( mean follow - up time 9.2 years , range 514 ) . seizure - free patients include those with sustained seizure freedom with or without aura since surgery ( blue ) and patients seizure - free at least the last year before follow - up ( green ) . overall , 117 ( 62% ) of the operated adults were seizure - free at long - term follow - up compared to 11 ( 14% ) of the controls ( p < 0.001 ) . fifty percent ( n = 93 ) of the operated adults had sustained seizure freedom at the 2-year and 41% ( n = 78 ) at the long - term follow - up . none of the controls was seizure - free for the whole time period . for the children , 44 ( 50% ) in the operated group were seizure - free the year before long - term follow - up , compared to 5 ( 38% ) in the control group ( not significant ) . fifty - three percent ( n = 46 ) of the operated children had sustained seizure freedom since surgery at the 2-year and 44% ( n = 39 ) at the long - term follow - up , compared to none in the control group . for both adults and children , the proportion with sustained seizure freedom at long term was significantly higher compared to the nonoperated patients ( p < 0.0005 ) . details on seizure outcome for the operated patients at 2 , 5 , and 10 years after epilepsy surgery are shown in table e-1 . eighty - seven percent of the adults as well as of the children who were seizure - free after 2 years were seizure - free at the 5- or 10-year follow - ups ( 95% confidence interval [ ci ] 7794 and 8095 , respectively ) . seizure outcomes for adults and children after different resection types are illustrated in table 2 . the most common resection type was tlr ( 81% in adults , 43% in children ) followed by frontal lobe resection ( flr ) in adults ( 12% ) and multilobe resection in children ( 20% ) . in adults , the best long - term seizure outcome was after tlr ( 63% seizure - free , sustained seizure freedom since surgery in 44% ) . in children the tlr outcome ( 60% seizure - free , 55% with sustained seizure freedom ) was matched by the long - term hemispherectomy results ( 60% seizure - free , all with sustained seizure freedom ) . if the extratemporal procedures are summed up , 31% of adults had sustained seizure freedom at long - term follow - up , compared to 36% of the children . seizure outcomes in the long term related to resection type the main histopathologic diagnoses were categorized as follows : hippocampal sclerosis ( hs , n = 45 ) , neurodevelopmental tumors ( n = 34 ) , low - grade astrocytomas ( n = 21 ) , cavernous hemangiomas ( n = 21 ) , malformations of cortical development ( n = 52 ) , gliosis ( n = 65 ) , and other ( n = 40 ) . highest seizure freedom rates were seen in hs ( 60% , 47% sustained since surgery ) and epileptogenic lesions ( 72% , 57% sustained since surgery ) ( table e-2 ) . the univariate relationship between long - term seizure freedom and the following baseline variables was explored for both operated patients and controls : epilepsy duration in percent of life length ( relative epilepsy duration , in odds ratio [ or ] increment units of 10% ) , 30 seizures / month , and presence of secondarily generalized tonic - clonic seizures ( sgtcs ) . for the operated patients , additional variables were positive mri , resection types , and histopathology ( figure 2 ) . for the controls , the univariate associations were nonsignificant although in the same direction as for the operated patients ( relative epilepsy duration , or 0.89 [ 95% ci 0.731.09 ] , 30 seizures / month , or 0.88 [ 95% ci 0.223.47 ] , and sgtcs , or 0.56 [ 95% ci 0.181.68 ] ) . in the surgical group , multivariate analysis was performed , where 30 seizures / month , or 0.40 ( 95% ci 0.230.69 ) , and relative epilepsy duration , or 0.91 ( 95% ci 0.831.00 ) , were negative predictors , while positive mri , or 1.96 ( 95% ci 1.083.55 ) , was a positive predictor of seizure - free long - term outcome . the auc value ( goodness of fit ) for the final multiple model was 0.66 . for the categorical variables with more than 2 categories ( resection type and histopathology ) , temporal lobe resections ( tlr ) and epileptogenic lesions ( epi les ) were chosen as reference categories . ci = confidence interval ; epi dur ( per 10% of life ) = epilepsy duration in percentage of life length , odds ratio units per 10% of life ; epileptogenic lesions = gangliogliomas , dysembryoplastic neuroepithelial tumors , cavernomas , and low - grade astrocytomas ; flr = frontal lobe resection ; he = hemispherectomy ; hs = hippocampal sclerosis ; mcd = malformations of cortical development ; mlr = multilobe resection ; or = odds ratio ; other = vascular malformations other than cavernomas , cysts , tuberous sclerosis , unknown histopathology ; p / olr = parietal or occipital lobe resection ; sgtcs = secondarily generalized tonic - clonic seizures . at baseline , 183 ( 66% ) of the patients had 2 aeds , 85 ( 31% ) had 1 aed , and 8 ( 3% ) had no aeds . the number of aeds used by the operated seizure - free patients decreased over time ( figure 3 ) . overall , 45 ( 54% ) patients who were seizure - free at 10-year follow - up had stopped aeds , compared to none of the seizure - free controls ( p < 0.0005 ) . more children than adults had stopped aeds ( 86% of the children and 43% of the adults , p = 0.002 ) . there was no significant association between the proportion of seizure - free patients who stopped aeds and resection type . among patients with seizures , the proportion with 2 aeds had increased from 77% preoperatively to 82% 10 years after surgery . number of antiepileptic drugs at the start of preoperative investigations , and after 2 , 5 , and 10 years for patients who were seizure - free at 5- or 10-year follow - up . since long - term results of epilepsy surgery can not be obtained from rcts , observational studies with defined quality criteria are needed . a number of requirements for studies on the prognosis after epilepsy surgery have been suggested . studies based on snesur meet many of these requirements , with a prospective design , representative study populations , a standard protocol for outcome measures , and prolonged longitudinal follow - up with few patients lost to follow - up . we found 63% of adults and 60% of children to be seizure - free after tlr at the long - term follow - up and most had continuous seizure freedom since surgery ( adults 41% , children 44% ) . as expected , the results were not as good after flr , with 44% of adults seizure - free ( sustained in 35% ) , and in children 27% seizure - free ( all sustained ) . this is still substantially better than for the patients who could not be operated ( 14% seizure - free adults , none sustained and 38% seizure - free children , none sustained ) . the adults who underwent other types of resections ( posterior or multilobar ) were few , and only 3 had sustained long - term seizure freedom . children who had undergone posterior resections or hemispherectomies had long - term seizure freedom in 55% and 60% , respectively ( sustained in 46% vs 60% ) . long - term outcome after resective epilepsy surgery is often reported cross - sectionally . in a meta - analysis from 2005 based on 78 studies , 66% of tlr patients , 46% of parietal or occipital lobe resection patients , and 27% of flr patients were seizure - free at follow - up 5 years postsurgery , but the authors point out that few studies reported sustained seizure freedom from surgery . a number of recent longitudinal long - term outcome studies report sustained seizure freedom after tlr . sustained seizure freedom is reported as engel 1 , engel 1a , or engel 1a+b and in a few studies as ilae class i and ii . sustained seizure freedom around 5 years postoperatively varies between 46% and 55% and 60% to 80% . among the studies with moderate rates of sustained seizure freedom , 2 of 4 are prospective , and our prospective study with 41% sustained seizure freedom at long - term follow - up after tlr in adults and 44% in children supports these results . a number of studies report cross - sectional long - term follow - up of pediatric epilepsy surgery , with seizure freedom in 50% to 82% of patients 5 to 12 years after tlr . only one study is longitudinal and reports sustained seizure freedom ( engel 1 ) in 54% of patients 5 years after tlr . there are few retrospective reports of long - term outcomes in patients after flr or other extratemporal resections . sustained seizure freedom 5 years after surgery varies in these studies from 15% and 27% to 52% , which can be compared to 31% ( adults ) vs 36% ( children ) in our cohort of 86 patients with varying extratemporal resections . long - term reports from population - based cohorts are sparse . in a retrospective cross - sectional comprehensive audit from ireland , national long - term seizure outcome data were reported . forty - four percent of patients were seizure - free 10 years after resective surgery , but the total number of operated patients could not be accounted for . a recent norwegian retrospective questionnaire study in children with a response rate of 70% reported 58% seizure - free after a mean of 7 years . however , sustained seizure freedom was not reported in these studies . in a recent systematic review , 20 studies comparing surgical results to those of a nonsurgical control group were identified ; 13 had a follow - up of at least 4 years . the controls were in general patients evaluated for surgery who for various reasons were not operated . overall 44% of surgical patients were seizure - free at follow - up ( in 90% of the studies , seizure freedom was reported at last follow - up or last year ) compared to 12% of medically treated patients . this is well in line with our findings of 58% seizure - free at last year of follow - up in the surgical group and 17% in the nonsurgical group , children and adults together . it must be remembered that patients who after preoperative investigations are considered ineligible for epilepsy surgery are not comparable to surgically treated patients , and they may have another disease course . it is difficult though to identify other reasonable controls for long - term follow - up studies , and from a clinical point of view they match the operated patients in many baseline variables . predictors for seizure freedom in the long term ( 4 years ) have been sought by several investigators . while some found no remaining predictors in multivariate analysis , the most commonly identified predictors are sgtcs at baseline and epilepsy duration or age at surgery . we found high baseline seizure frequency and relative epilepsy duration to be negatively and positive mri to be positively related with long - term seizure freedom . epilepsy duration before undertaking presurgical investigation  has repeatedly been shown not to have shortened significantly over the years . these results from long - term outcome studies underline the importance of earlier identification of good candidates for resective epilepsy surgery . there is no common swedish protocol for discontinuation of aeds in seizure - free patients . most adults continue aeds the first 2 postoperative years ; further decisions about withdrawal are taken individually . we found that 43% of seizure - free adults and as many as 86% of seizure - free children had discontinued aeds after 10 years . the reasons for this difference are unknown ; possibly , social consequences of seizure relapse are of greater importance to adults ( e.g. , driving or occupation ) , who therefore may choose to continue aeds . by contrast , more concern about adverse effects of aeds on the developing brain in children may lead to earlier decisions about withdrawal . the proportion of seizure - free adults and children in whom aeds have been withdrawn after successful epilepsy surgery varies widely across studies . in a meta - analysis from 2007 , 9 studies were identified and a pooled analysis showed that 27% of seizure - free children and 19% of seizure - free adults had discontinued aeds at a mean follow - up of 7 years . however , in an indian study , aed withdrawal was systematically planned for all seizure - free patients after tlr and was successful in 63% of 258 patients who were followed for 5 years . very similar to our results in children , a canadian study found that 82% of seizure - free children had stopped aeds 10 years after surgery . possible reasons for these differences in patient decisions about aed cessation may include socioeconomic and cultural differences , as well as how doctors inform their patients , which partly depends on their own assessment of recurrence risk . the timetostop study showed that early withdrawal of aed in children did not influence the long - term seizure outcome but could unmask incomplete surgical success sooner , and the authors suggest that it is now time to plan an rct of aed withdrawal after epilepsy surgery in children . like most , if not all , observational outcome studies after epilepsy surgery , we had no masking in seizure outcome assessment . our nonoperated control group was recruited from the 3 largest of the swedish epilepsy surgery centers and is hence not a national sample . on the other hand , we have a regional referral system and it is reasonable to assume that this sample is representative of the population of patients who are evaluated for surgery in sweden but not operated . patients need detailed counseling before deciding to undergo irrevocable brain surgery . realistic expectations concerning long - term outcomes are part of the information they need to consider . this prospective population - based study contributes to this knowledge and supports seizure outcome data from prospective single - center studies , and also shows that a greater proportion of seizure - free patients than in most studies had stopped aed treatment 10 years after surgery . funded by grants from the swedish research council ( grant 521 - 2011 - 169 ) , the sahlgrenska academy at gothenburg university through the lua / alf agreement ( grant alfgbg137431 ) , the gothenburg foundation for neurological research , the gothenburg medical society , the margaretahem foundation , and an unconditional research grant from glaxosmithkline to anna edelvik . k. malmgren served on an educational advisory board for ucb and has received speaker 's honoraria from ucb .