Population-Based Analysis of Morbidity and Mortality Following Surgery for Intractable Temporal Lobe Epilepsy in the United States FREE

Accounting for approximately 1% of the global burden of disease due to disability, with a burden of illness similar to that of lung cancer in men and breast cancer in women, epilepsy affects 0.5% to 1% of the world's population and is the second leading cause of mental health disability in the United States.^1- 3Despite the efficacy and availability of antiepileptic drugs, as many as 40% of patients with epilepsy will continue to have seizures even after at least 2 adequate trials of antiepileptic drugs; this accounts for more than 75% of the cost of epilepsy in the United States.^4- 7

Temporal lobe epilepsy (TLE) is both the most common form of epilepsy and the most likely to remain refractory to medication.^8- 9 Patients with intractable TLE often benefit from surgical management via temporal lobectomy. Results from several observational studies and the only randomized controlled trial all demonstrate that surgical intervention is far superior to continued medical treatment in this patient population.^1,10 Unfortunately, despite these data, only a small number of patients are referred for epilepsy surgery evaluation, most of whom have already had many years of seizures.^10- 12

A possible impediment to increased referrals for epilepsy surgery evaluation may be the perceived degree of morbidity and mortality following temporal lobectomy. To address this issue on a nationwide level, a large inpatient database was used to evaluate the overall morbidity following temporal lobectomy for intractable TLE in the United States over an extended period. Subset analyses of morbidity were performed to assess the existence of racial disparities among this patient population because racial disparities have recently been reported regarding access to surgical treatment for intractable TLE.^13- 14

The Nationwide Inpatient Sample (NIS) hospital discharge database (overview available at http://www.hcup-us.ahrq.gov/nisoverview.jsp) covering 1988 through 2003, obtained from the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality (Rockville, Maryland), was used as the data source for this study.¹⁵ The NIS represents approximately 20% of all inpatient admissions to nonfederal hospitals in the United States. For these years, the NIS contains data on 100% of discharges from a stratified random sample of nonfederal hospitals in 8 to 35 states (number of states increased year to year from 1988-2003), approximating a 20% representative subsample of all US nonfederal hospital discharges. Because the NIS contains data on all patients discharged from sampled hospitals during the year (regardless of payer or patient age), it can be used to obtain the annual total volume of specified procedures at individual hospitals. Additionally, the surgeon who performed the principal procedure following admission is identified by a unique masked code.

The NIS database was searched to identify an admission to undergo temporal lobectomy for intractable TLE. Admissions having a patient age of 18 years or older, a diagnosis code of 345.41 (intractable partial epilepsy with impairment of consciousness) or 345.51 (intractable partial epilepsy with mention of impairment of consciousness), and a primary procedure code of 01.53 (brain lobectomy) were included.

In addition to race, patient age, sex, median household income for postal (zip) code of residence, primary payer (Medicare, Medicaid, private insurance, self-pay, no charge, or other), type of admission (emergency, urgent, or elective), and admission source (emergency department, transfer from another hospital, transfer from long-term care, or routine) were coded in the NIS data. The subset analysis focused on comparisons between that subset and nonsubset persons included (eg, Hispanic vs non-Hispanic); any patient with missing race was viewed as white.

The number of available beds (small, medium, large), teaching status, hospital region (Northeast, Midwest, South, West), and location (rural, urban) were coded in the NIS data. Surgeon volumes of anterior temporal lobectomy (ATL) for intractable TLE were derived by counting the cases for each identified surgeon in the database. Surgeon volume was analyzed as either low caseload (<3 ATL per year) or high caseload (≥3 ATL per year).

The characteristics of patients, providers, and hospitals were summarized by descriptive statistics. Results were expressed as mean (standard deviation, median, and range) for continuous variables and frequency (percentage) for categorical variables. Rao-Scott modified χ² tests for the univariate comparisons were performed on the categorical variables using PROC SURVEYFREQ from SAS version 9.1 (SAS Institute, Cary, North Carolina). To examine the association between the outcomes of postoperative morbidity or adverse discharge disposition and the characteristics of patient age, sex, race, payer, admission type, income, and caseload of hospital, we first fitted a separate logistic regression model for each characteristic against the outcome and reported the odds ratio (OR) with 95% confidence interval (CI) for each characteristic. We then fitted a multiple logistic regression model on the outcome with the aforementioned characteristics as covariates and reported the adjusted ORs with 95% CIs for each characteristic in the multivariate analysis. Extrapolations to the entire US population were adjusted for the NIS stratified survey method in the logistic regression models by using PROC SURVEYLOGISTIC in the SAS statistical software program. All probability values shown are 2-tailed. A P value less than .05 was accepted as significant.

Patients were evaluated examining TLE as a primary diagnosis, 1 of the top 3 diagnoses, and 1 of the top 15 diagnoses. Overall morbidity was evaluated as a summation of postoperative morbidity, in-hospital mortality, and adverse discharge disposition. Adverse discharge disposition was defined as hospital discharge to any place other than home (eg, short-term rehabilitation, long-term rehabilitation, hospice).

For subset analysis, ORs were assessed for in-hospital mortality, postoperative morbidity, and adverse discharge disposition individually and in combination for assessment of morbidity. Potential complications of temporal lobectomy were identified using the following codes: postoperative neurological complications (including those secondary to infarction or hemorrhage), 997.00 to 997.09; hematoma complicating a procedure, 998.1 to 998.13; bilateral visual field defects, 368.46 and 368.47; diplopia, 368.2; postoperative infection, 998.5, 998.51, and 998.59; hydrocephalus, 331.3 to 331.4; ventriculostomy placement, 02.2; deep vein thrombosis, pulmonary embolism, or inferior vena cava filter placement, 415, 415.11 to 415.19, 453.8, 453.9, and 38.7; and transfusion of packed red blood cells, 99.04. The effect of general medical comorbidity was assessed using a set of 25 medical comorbidity markers previously described, which were tabulated to provide a single comorbidity score ranging from 0 to 25.^16- 17

From 1988 through 2003, the NIS database contained 10 723 admissions for adults with intractable TLE, of whom 736 received ATL. Patients were treated at a total of 190 hospitals; 70% of hospitals were classified as large bed size, and approximately two-thirds received care by a surgeon performing at least 3 temporal lobectomies per year; the remaining clinical characteristics are depicted in Table 1. Information on the treating surgeon was available for 51.8% of the admissions, with 84 treating surgeons identified in the database. The vast majority of patients receiving ATL had no medical comorbidities, and fewer than 3% had more than 1 comorbidity (Table 2). No patient receiving ATL had a comorbidity score higher than 3.

Of the 677 patients with available discharge data, 3 required short-term rehabilitation and 24 required long-term rehabilitation, yielding a total adverse discharge disposition of 4% (27 of 677). The incidence of postoperative morbidity was 8% (Table 3). Of the postoperative complications following ATL for TLE, the most common was postoperative neurological complications (2.7%), followed by transfusion of packed red blood cells (2.3%), hematoma (1.2%), homonymous or heteronymous hemianopsia (1.1%), postoperative infection (0.8%), diplopia (0.7%), hydrocephalus (0.4%), and ventriculostomy placement (0.1%). No patient had a deep vein thrombosis or pulmonary embolism or required inferior vena cava filter placement, and there was no mortality (Table 3). The incidence of postoperative morbidity directly correlated with increasing patient comorbidity score (Table 2). The overall morbidity, defined as patients with postoperative morbidity and/or adverse discharge disposition, was 10.8% (73 of 677).

Multivariate analysis revealed that private insurance (OR = 0.52; 95% CI = 0.28-0.98; P = .04) and routine admission type (OR = 0.36; 95% CI = 0.18-0.73; P = .005) independently predicted significantly reduced morbidity (Table 4). Conversely, older age independently predicted increased postoperative morbidity (OR = 1.04; 95% CI = 1.01-1.07; P = .03); each year of age affected the likelihood of postoperative morbidity by [(1.04^{Age of Patient − Age of Comparison Patient}) − 1] × 100, such that a 40-year-old was 4% more likely to have postoperative morbidity than a 39-year-old, 32% less likely than a 50-year-old, and 48% more likely than a 30-year-old. Neither surgeon volume, hospital bed size, sex, African American race, Hispanic race, or income was predictive of postoperative morbidity (Table 4 and Table 5).

Examination of adverse discharge disposition revealed that only private insurance (OR = 0.31; 95% CI = 0.12-0.81; P = .02) and patient age (OR = 1.08; 95% CI = 1.02-1.13; P = .004) were independently predictive of adverse discharge disposition; each year of age affected the likelihood of adverse discharge disposition by [(1.08^{Age of Patient − Age of Comparison Patient}) − 1] × 100. No other variable was predictive of adverse discharge disposition (Table 6 and Table 7).

Despite the success of temporal lobectomy in the treatment of intractable TLE, a large majority of patients with TLE are not referred for epilepsy surgery evaluation.^10- 11 Although previous analysis of a large number of temporal lobectomy series places the risk of permanent postoperative morbidity at 1% to 10% (without including adverse discharge disposition), there may be a reticence among some providers to refer patients for surgical intervention.^10,18 Furthermore, recent studies have indicated that racial disparities exist with regard to access to temporal lobectomy among patients with TLE.^13- 14 Consequently, this study sought to evaluate the morbidity of temporal lobectomy on a nationwide scale and to assess the presence or absence of health care disparities in postsurgical morbidity.

The findings of this study reveal that the incidence of postoperative morbidity following temporal lobectomy for TLE is 8%, well within the range quoted by several studies, and includes several complications that may be transient in nature. The incidence of adverse discharge disposition is 4%, and the overall morbidity (postoperative morbidity and/or adverse discharge disposition) is 10.8%, with no mortality. The risk of postoperative morbidity increases with increasing medical comorbidity and independently increases with increasing patient age, lack of private insurance, and nonroutine hospital admission.

As intriguing as these results are, it is important that they be tempered by the limitations of this study. The first and most obvious limitation is the retrospective nature of the study, which necessitated the use of ORs instead of relative risk for statistical interpretation of the data. The second limitation is the incompleteness of the NIS in representing the United States; although it is by far the most comprehensive database available spanning 1988 to 2003, it only represents 20% of all inpatient admissions in the United States and does not include federal hospitals. Another limitation is the inpatient nature of the database, which limits the ability of this study to identify delayed postoperative complications. A fourth limitation is that the nature of the database limits the ability of this study to determine whether morbidity results in transient or permanent postoperative deficits. Finally, because more than 99% of patients in this study had fewer than 3 medical comorbidities, the results from this study should not be applied universally without regard to a prospective patient's underlying comorbidity status.

Despite the limitations of this study, the results shed light on an important fact: temporal lobectomy for intractable TLE in the United States had low morbidity, with no mortality over a 16-year period. This finding, in combination with those of several other studies, confirms that ATL should be viewed by the general medical and societal community as safe and that patients with intractable TLE should be referred for epilepsy surgery evaluation, particularly if they have 3 or fewer medical comorbidities. Furthermore, because neither African American nor Hispanic race predisposes toward increased postoperative morbidity, increased measures should be taken to address previously reported racial disparities in access to ATL.^13- 14

Morbidity following temporal lobectomy for intractable TLE in the United States is low and should not preclude patients with TLE from being referred for epilepsy surgery evaluation regardless of sex, race, insurance status, or income. Medical comorbidity correlates with the incidence of postoperative morbidity. Younger age and private insurance status independently predict decreased postoperative morbidity and better hospital discharge disposition.

Correspondence: Shearwood McClelland III, MD, Department of Neurological Surgery, Boston University School of Medicine, 88 E Newton St, Robinson 4, Boston, MA 02118 (drwood@post.harvard.edu).

Accepted for Publication: December 9, 2010.

Published Online: February 14, 2011. doi:10.1001/archneurol.2011.7

Author Contributions: Dr McClelland had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: McClelland, Guo, and Okuyemi. Acquisition of data: McClelland and Okuyemi. Analysis and interpretation of data: Guo and Okuyemi. Drafting of the manuscript: McClelland, Guo, and Okuyemi. Critical revision of the manuscript for important intellectual content: McClelland, Guo, and Okuyemi. Statistical analysis: Guo. Obtained funding: Okuyemi. Administrative, technical, and material support: Okuyemi. Study supervision: McClelland.

Financial Disclosure: None reported.

Funding/Support: Funding for statistical analysis was provided by the Department of Family Medicine and Community Health, University of Minnesota Medical School (Dr Guo).