Epilepsia, 44(12):1568���1572, 2003 Blackwell Publishing, Inc. C 2003 International League Against Epilepsy Long-term Outcome of Nonsurgical Candidates with Medically Refractory Localization-related Epilepsy ���Linda M. Selwa, ���Shelley L. Schmidt, ���Beth A. Malow, and ���Ahmad Beydoun ���Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, ���Department of Neurology, Vanderbilt University, Nashville, Tennessee, both in U.S.A. Summary: Purpose: Epilepsy surgery can result in complete seizure remission rates of upto 80% in patients with mesial tem- poral 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 re- fractory localization-related epilepsy cannot be offered surgical resection because of inadequate localization of the epileptogenic zone, documentation of bilateral ictal onsets, or functionally im- portant 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 refrac- tory partial epilepsy who were evaluated for possible epilepsy surgery but deemed to be inadequate surgical candidates. Methods: 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 ulti- mately offered surgical treatment at the University of Michigan from 1990 through 1998. We assessed changes in seizure fre- quency and type, imaging characteristics, ictal recordings, in- terim medication history, and subjective changes in quality of life. Results: 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 evalua- tion. 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. Conclusions: A surprisingly large number of patients we sur- veyed, 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. Key Words: Epilepsy���Partial���Temporal lobe���Efficacy���Quality of life. Although the natural history of localization-related epilepsy is incompletely understood, recent data indicate that treatment response is likely to correlate with the eti- ology of the epilepsy. Temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) seems to be the most re- fractory to medical treatment (1), with the likelihood of complete remission ranging from 11% (2) to 42% (3). A better prognosis with medical management has been asso- ciated with other types of partial epilepsies. For instance, cryptogenic partial epilepsy remitted at a rate of 45% (2), and patients with lesional epilepsy secondary to arteri- ovenous malformations had a 78% chance of becoming seizure free (3). Other prognostic variables include age Accepted August 4, 2003. Address correspondence and reprint requests to Dr. L.M. Selwa at University of Michigan, Department of Neurology, 1500 East Medical Center Drive, 1914/0316 Taubman, Ann Arbor, MI 48109-0316, U.S.A. E-mail: lmselwa@umich.edu at seizure onset, number of generalized seizures, duration of epilepsy, and severity of associated cognitive or psy- chiatric disturbances (4���7). Secondary epileptogenesis is thought to be most relevant to cases of bilateral tempo- ral epilepsy and secondary bilateral synchrony (8), and some concern is expressed that partial epilepsy may be a progressive disease in these cases. For patients with MTS, surgical removal of the epilep- togenic zone is associated with seizure remission in 70��� 80% (9). In the only controlled trial (10), surgical manage- ment was shown to be clearly superior to medical man- agement in a group of patients with TLE. In this care- fully selected mesial temporal epilepsy group, only 8% had seizure control at 1 year with aggressive medication trials. However, surgical management does not yet deliver as much of an advantage in other types of localization- related epilepsy. For instance, only 32% (11) to 36% (12) of patients with independent bilateral temporal ictal 1568

LONG-TERM OUTCOME WITH LRE 1569 onsets achieved seizure freedom after unilateral palliative resections of the more active side. Comparable estimates of seizure freedom after surgery were reported for patients with nonlesional extratemporal epilepsy, with a range be- tween 42 and 45% (13,14). We undertook this study to evaluate the outcome of medical treatment in a group of patients with medically refractory localization-related epilepsy who were evalu- ated for possible epilepsy surgery but deemed to be inade- quate surgical candidates. This type of group has not previ- ously been evaluated. We specifically analyzed changes in seizure frequency, as well as the patients��� own perceptions of their overall quality of life. We also tried to identify pre- dictive factors that could help discriminate between those with the best and the poorest outcomes. METHODS Selection of patients Study candidates were identified by using the Epilepsy Surgery Database from the Department of Neurology at the University of Michigan. The database includes all patients with medically refractory localization-related epilepsy being considered for surgical intervention. The target population for this study consisted of patients evalu- ated for possible epilepsy surgery between 1990 and 1998 and deemed to be inappropriate surgical candidates. Pa- tients who declined surgery on the basis of the likelihood of remission quoted, or on the basis of improvement in their condition were not included. At our center, the deci- sion about surgical management is based on a consensus decision at a refractory epilepsy conference. Some patients with unilaterally predominant (usually ������70%) bilateral TLE have been offered palliative resections. Study design This study was approved by the University of Michigan Institutional Research Review Board. For each patient, we collected the variables of interest by reviewing the med- ical records, and after informed consent, we conducted a follow-up telephone interview. The data collected from the medical records included demographic variables, risk factors for epilepsy, and re- sults of the diagnostic workup. Specifically, we collected the age at seizure onset, age at enrollment into the study, and the time since evaluation for epilepsy surgery. Risk factors for epilepsy, including febrile seizures, closed head injury, or CNS infections were ascertained. In addition, we evaluated the monthly seizure frequency, epilepsy treat- ment regimen, employment, and driving status at or near the time of their first admission for the inpatient CCTV- EEG monitoring. We also recorded the results of diagnos- tic tests, including neuropsychometric testing, ictal and in- terictal CCTV-EEG, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT if performed), and positron emission tomography (PET if performed). Based on those data, we noted the reason those patients were not deemed to be appropriate surgical candidates. We conducted a telephone interview with patients and family members to assess their situation at the time of follow-up. We specifically inquired about their current monthly seizure frequency, changes in seizure semiology, current treatment regimen for epilepsy, and whether a va- gus nerve stimulator (VNS) was implanted. We defined seizure freedom as ���1 year without any seizures recog- nized by the patient or family. We also assessed quality of life including driving status, current employment status, and asked the patients to rate on a 5-point global categor- ical scale their current level of satisfaction with life since their evaluation for possible epilepsy surgery. In addition, we inquired about psychiatric intervention and availability of psychosocial support. Analysis We analyzed the change in seizure frequency at the time of follow-up compared with those at the time of presur- gical evaluation with paired t tests. Correlations between specific variables and likelihood of remission were ana- lyzed with one-way analysis of variance (ANOVA). Sta- tistical significance was set at p values of 0.05. We used a Pearson���s test to analyze the possible significance of sex to outcome, and used the Mann���Whitney test to evaluate the correlation of seizure frequency with outcome. RESULTS Demographics A total of 47 patients identified through our surgical database qualified for participation in the study. At the time of follow-up, four patients could not be located, seven refused or were unable to participate in the phone survey, and two patients were deceased. The remaining 34 patients (19 women, 15 men) were the subjects of this study. The reasons for rejection of surgical candidacy included diffuse or inadequately localizing ic- tal onsets, often associated with uninformative SPECT or PET studies (18 of 34 53%), bilateral independent tem- poral ictal onset, (usually very close to 50% onset in each hemisphere with invasive monitoring), with normal or bi- laterally abnormal neuroimaging studies (13 of 34 38%), epileptogenic zones involving primary language cortex (two of 34 6%), and one (3%) with evidence for bilateral temporal dysfunction who failed Wada testing even after a repeated superselective injection. Twenty-three (68%) of the 34 patients underwent invasive intracranial monitoring in unfruitful attempts to localize the epileptogenic zone. Eight of the invasive monitoring procedures involved grid or strip electrodes in the frontal (four), occipital (one), lat- eral temporal (two), and insular (one) regions. Fifteen of the intracranially studied patients had bilateral temporal depth electrodes. Epilepsia, Vol. 44, No. 12, 2003