Amobarbital

Objectives: To determine the characteristics, seizure outcomes, and quality-of-life outcomes for military beneficiaries undergoing partial temporal lobectomy for refractory epilepsy at the only U.S. military medical center with a comprehensive epilepsy surgery program. Methods: The records of all 84 patients treated with partial temporal lobectomy between 1986 and 2000 at Walter Reed Army Medical Center were retrospectively reviewed. Outcome measures included seizure frequency according to the Engel classification system, driving, employment, anticonvulsant use, and military service. Results: The study cohort consisted of 72 military dependents, 10 active duty military members, and 2 military retirees. Two years after surgery, 65 (92%) of 71 patients had seizure improvement (Engel classes I-III) and 46 (66%) of 71 had seizure remission (Engel class I). Driving and employment rates increased after surgery, whereas anticonvulsant use decreased. Five (50%) of 10 active duty patients achieved seizure remission postoperatively and continued to serve in the Armed Forces. Active duty patients had a later age of seizure onset, shorter duration of epilepsy, and greater proportion of lesional epilepsy, compared with nonactive duty patients. Conclusions: Epilepsy surgery outcomes in the U.S. military are similar to those reported from nonmilitary centers, with the majority of patients experiencing seizure remission and improvements in quality-of-life measures. Complete seizure remission after successful anterior temporal lobectomy enables some active duty military members to continue service in the U.S. Armed Forces.

Introduction

Anterior temporal lobectomy is an established treatment for refractory temporal lobe seizures, the most common type of intractable epilepsy among adults, with approximately 50 to 70% of patients being rendered seizure-free by this procedure,1-5 A recent controlled trial of surgical treatment versus medical treatment for refractory temporal lobe epilepsy demonstrated the superiority of surgery, with 58% of patients being seizure-free 1 year after surgery compared with only 8% of patients who received medication alone.4 Improvements in quality-of-life measures after temporal lobectomy have also been reported.1,5-7

Epilepsy surgery outcomes have not been described for a military population. We report the characteristics, seizure outcomes, quality-of-life outcomes, pathological findings, and prognostic factors for patients undergoing partial temporal lobectomy for refractory temporal lobe epilepsy in a major U.S. military hospital. The findings are discussed in terms of their implications for the management of intractable epilepsy among military members.

Methods

Patients

Walter Reed Army Medical Center has been designated by the U.S. Department of Defense as the Center of Excellence within the military health care system for epilepsy surgery. It is currently the only U.S. military medical center with a comprehensive epilepsy surgery program. Between 1986 and 2000, 84 patients underwent epilepsy surgery on the temporal lobe at this center. All patients had complex-partial seizures, with or without secondarily generalized seizures, refractory to at least two medications. Seizures were present for at least 1 year and occurred more than once per month. All patients were determined to have seizures arising from a single temporal lobe based on an extensive preoperative evaluation (described below).

Preoperative Evaluation

All patients underwent a standard preoperative evaluation consisting of a comprehensive history and neurological examination, interictal scalp electroencephalography (EEG), videoEEC monitoring with surface electrodes, neuropsychological testing, intracarotid amobarbital testing (Wada), and brain imaging. Brain magnetic resonance imaging (MRI) was performed for 80 patients. Brain computed tomography (CT) was performed for four patients who were evaluated before MRI availability. Fifteen of 18 patients without evident abnormalities on brain MRI scans also underwent an interictal/ictal single-photon emission CT study using hexamethylpropyleneamine oxime. Subdural recording was performed for 37 patients with lateralizing but poorly localizing surface EEG monitoring results. The subdural recording covered the lateral frontal cortex and lateral, medial, and inferior temporal cortex. When surgery was to be performed on the language-dominant side, the language cortex was mapped either with cortical stimulation of the awake patient in the operating room or, more often, with subdurally implanted grid electrodes on the ward with video-EEG recording. Informed consent was obtained for all invasive procedures.

Surgery

Epilepsy surgeons (R.G.E., K.K., L.M.) assigned to Walter Reed Army Medical Center performed the surgery. Piecemeal resections were performed for the majority of patients. Seven patients had en bloc resections. Intraoperative electrocorticography was used for more than one-half of the patients, especially in earlier cases. The procedure in the majority of cases was standard anterior temporal lobectomy and included medial temporal structures. The margins extended posteriorly 3.5 to 4 cm in dominant lobe resections and 5 to 6 cm in nondominant lobe resections. Eight patients had selective amygdalohippocampectomy.

Outcomes

All patients were evaluated preoperatively and monitored postoperatively by a single neurologist (B.J.). Postoperative follow-up evaluations were performed bimonthly in the epilepsy clinic for the first 6 months, then twice per year for 2 years, and then yearly. Another neurologist (J.C.E.) retrospectively reviewed all charts for outcome measures. Seizure outcomes were assessed according to the Engel classification system,8 in which class I indicates an absence of seizures impairing consciousness during the previous year, class II indicates rare disabling seizures, class III indicates more than rare seizures but at least a 50% reduction in seizures compared with baseline, and class IV indicates no improvement.

Employment status was determined in the year before surgery and then again at the last follow-up assessment. Employment was considered to be any job performed outside the individual's residence, either part time or full time, for which monetary payment was received. Voluntary homemakers and students were not considered. Driving status was determined by patient self-report for the year before surgery and then again postoperatively at the time of the last follow-up evaluation.

Pathology

Tissue specimens were examined by a panel of at least two staff neuropathologists at the Armed Forces Institute of Pathology (Washington, DC).

Statistical Analyses

Fisher's exact test or χ^sup 2^ test was used for categorical data and the t test was used for continuous data. A p

Results

Patient characteristics are summarized in Table I. Most of the patients were female and were dependents of military personnel. Ten patients were on active duty in the Armed Forces at the time of surgery, with severe restrictions on their duties in accordance with epilepsy.

Seizure outcomes were available for 81 (96%) of 84 patients after a follow-up period of 1 year and for 71 (88%) of 81 patients after a follow-up period of 2 years. The mean follow-up period was 4.2 years. Seizure outcomes according to postoperative year are shown in Table II. Two years after surgery, 65 (92%) of 71 patients had significantly improved seizures (Engel class I, II, or III) and 46 (66%) of 71 had seizure remission (Engel class I).

At least one seizure occurred during the follow-up period for 34 (42%) of 81 patients. The initial seizure recurrence occurred within 6 months after surgery for 15 (44%) of 34 patients, within 1 year for 22 (65%) of 34, within 2 years for 29 (86%) of 34, and within 3 years for 33 (97%) of 34. The latest seizure recurrence occurred 5 years after surgery. Four (80%) of five patients whose initial seizure recurrence occurred more than 2 years postoperatively subsequently became seizure-free for at least 2 years, enabling them to be reclassified as Engel class I. In contrast, only 8 (27%) of 30 patients whose initial seizure relapse occurred within 2 years after surgery had seizure remission at the last follow-up evaluation (p

Several correlations between preoperative diagnostic tests and postoperative seizure outcomes were observed. Forty-five (75%) of 60 patients with unilateral interictal spikes on surface EEG scans had class I outcomes, whereas only 6 (46%) of 13 patients with bilateral temporal lobe spikes had class I outcomes (p = 0.04). Forty-nine (78%) of 63 patients with a temporal lobe abnormality on any imaging study (MRI, CT, or single-photon emission CT) had class I outcomes compared with only 8 (50%) of 16 patients with no temporal lobe abnormality on imaging (p = 0.014). The probability of postoperative seizure remission was highest for patients with concordant interictal EEG and neuroimaging abnormalities (41 of 47 patients, 87%). Invasive EEG recording defined the seizure focus for several patients with failed surface EEG, but there was no significant difference in seizure outcomes between this group and the group with only surface EEG recording.

Neuropathological findings of resected tissue were available for 80 (95%) of 84 patients. The most common pathological diagnosis was mesial temporal sclerosis-gliosis (38 of 80 patients, 47.5%), followed by neoplasm (18 of 80 patients, 22.5%; 9 astrocytomas, 4 gangliogliomas, 3 dysembryonic neuroepithelial tumors, 1 oligodendroglioma, and 1 hamartoma), vascular malformation (9 of 80 patients, 11.3%; 5 cavernous angiomas, 3 arteriovenous malformations, and 1 unspecified venous anomaly), dysplasia (5 of 80 patients, 6.3%), and ischemia (2 of 80 patients, 2.5%). No pathology was identified in 8 (10%) of 80 cases. Seizure outcomes according to pathology are summarized in Table III. Mesial temporal sclerosis correlated with postoperative seizure remission (p

Quality-of-life indicators are summarized in Table IV. Driving and employment rates significantly increased after surgery, whereas anticonvulsant use significantly decreased. Postoperative driving status was strongly associated with seizure outcomes, with 23 (96%) of 24 driving having favorable seizure outcomes compared with only 5 (31%) of 16 not driving (p

No deaths occurred in the perioperative period or during the follow-up period. Significant long-term adverse effects occurred for 4 (5%) of 84 patients, including hemiparesis for 2 patients, disabling memory impairment for 1 patient, and dysphasia for 1 patient. Both cases of postoperative hemiparesis occurred with en bloc resections.

As summarized in Table V, there were several differences between active duty patients and non-active duty patients. Active duty patients had a later onset of epilepsy and a shorter latency to surgery. No active duty patients had seizure onset in infancy or childhood. The proportion of patients with lesional epilepsy (i.e., epilepsy attributable to a tumor or vascular anomaly) was greater in the active duty group (6 of 10 patients, 3 with low-grade neoplasms and 3 with vascular malformations). No active duty members had mesial temporal sclerosis.

All 10 of the active duty patients were in the process of being medically discharged from the military at the time of surgery, in accordance with military retention standards pertaining to epilepsy. However, 5 (50%) of 10 military members achieved complete postoperative seizure remission without adverse effects and were therefore retained on active duty. Their duty restrictions were gradually reduced over a 2-year period. We are not aware of any adverse effects of epilepsy surgery on their military duty performance. In contrast, the 5 (50%) of 10 active duty patients who had incomplete seizure remission, and were therefore incapable of full military duty, were discharged from the military for failure to meet medical retention standards.

Discussion

This is the first report of epilepsy surgery outcomes in a military population. We found that 2 years after partial temporal resection, 66% of patients experienced seizure remission and an additional 26% experienced seizure improvement. Surgery also improved several quality-of-life indicators. The seizure outcomes, complication rates, and quality-of-life outcomes were similar to those reported in contemporary studies from nonmilitary centers.1-7

The small proportion of active duty military members in our series reflects current military guidelines stating that medically refractory epilepsy is disqualifying for both enrollment and retention in the U.S. Armed Forces.9-11 Prospective military enlistees who have a history of seizures must be seizure-free without medications for 5 years and must have recent normal EEG results to qualify for enlistment. Soldiers in the U.S. Army who develop epilepsy may remain on active duty if their seizures are fully controlled with a single medication, without significant side effects.9 Strict restrictions on their military duties, activities, and assignments are imposed for 1 year, followed by another year of no assignment to areas where medical care is unavailable.9 In contrast, a diagnosis of epilepsy is grounds for medical discharge from the U.S. Navy. Air Force members with seizures are strictly disqualified from flying duty and must undergo a medical evaluation board hearing to determine whether they are retained on active duty.11

Current U.S. Army medical retention standards, which were last updated before wide implementation of surgical treatments for epilepsy, do not specifically address the role of surgery in the management of medically refractory seizures among soldiers.9 It has been our experience that most active duty military members with medically refractory epilepsy, especially those with nonlesional epilepsy, are medically discharged from the military without consideration for epilepsy surgery.

The relatively small number of active duty service members in our surgical cohort may also reflect a perception among neurologists caring for military members that epilepsy surgery either is ineffective or is associated with side effects incompatible with military service. To the contrary, we found that one-half of the active duty military members who underwent temporal lobectomy became seizure-free without adverse effects and were thereby able to continue their service in the Armed Forces, with gradual lessening of their activity limitations and assignment restrictions. These results suggest that surgical treatment of medically refractory epilepsy is a practical option for selected active duty military members.

Military members who are medically discharged from active duty because of epilepsy are eligible for care through the Veterans Affairs health care system. Several Veterans Affairs hospitals have comprehensive epilepsy surgery centers. Maganti et al.12 recently reported the outcomes of anterior temporal lobectomy for a series of U.S. veterans with medically refractory epilepsy, many of whom had been medically discharged from active duty because of epilepsy. They found that 66% of veterans had seizure remission after surgery. A number of such patients might have been eligible for retention on active duty if they had been treated with surgery before medical discharge from the military.

Most (86%) of the patients in our cohort were dependents (mostly wives) of active duty military members. In many respects, these patients do not differ significantly from those treated by civilian epilepsy centers. However, military dependents with epilepsy may be confronted with psychological, emotional, and social factors unique to the military population. Frequent geographic relocation, sometimes to remote regions of the world where specialized medical care is not readily available, may perpetuate the medical and psychosocial disability of military dependents with epilepsy by fragmenting medical care, disrupting the patient's social support network, and diminishing employment and education opportunities. The long duration of epilepsy before surgery (19.7 years) observed for military dependents in our cohort might be a manifestation, in part, of discontinuous neurological care associated with frequent geographic relocation. The Exceptional Family Member Program, a Department of Defense initiative established in 1996 that attempts to accommodate military dependents with special medical needs by assigning their military sponsor to geographic regions where specialized medical care is available, should facilitate the treatment of refractory epilepsy among military dependents.13

Another challenge faced by military spouses with epilepsy is the regular prolonged absence of their military sponsor, who is usually the only family member with driving privileges. Reinstatement of driving privileges after successful epilepsy surgery, which occurred for 60% of the patients in our cohort, is therefore expected to have a major beneficial impact on the military spouse's functional independence.

Predicting long-term seizure outcomes is critical for military physicians who must determine whether, and in what capacity, military members treated for epilepsy can safely serve on active duty. Similar to previous studies from nonmilitary centers, we found seizure outcomes during the first 2 postoperative years to be the strongest predictor of long-term seizure outcomes.1,3,14-17 The presence of unilateral, interictal, epileptiform discharges on surface EEG scans, concordant imaging abnormalities, and mesial temporal sclerosis in pathology examinations were all associated with high rates of postoperative seizure remission, reinforcing the previously reported prognostic value of these findings.5,14-16 Based on the aforementioned data, we recommend that patients serving in the Armed Forces remain on restricted duty for at least 2 years following temporal lobectomy for refractory epilepsy. Those who are seizure-free during this 2-year period have a low likelihood of future seizure relapse and could reasonably be returned to duty. Conversely, individuals who experience seizure recurrences within 2 years after surgery, especially those with a paucity of other positive prognostic factors, are unlikely to achieve long-term seizure remission and should be medically discharged from the military. These empirical (and unofficial) guidelines for the administrative management of active duty patients undergoing epilepsy surgery are concordant with current U.S. Army medical retention standards for epilepsy.9

In conclusion, the current study provides evidence that temporal lobectomy is an effective, well-tolerated treatment for refractory temporal lobe epilepsy for selected military service members, military dependents, and military retirees. The observation that some military members successfully resume military service, under the demanding conditions of full active duty, is a remarkable testament to the potential benefits of epilepsy surgery. Current military guidelines for managing military members with epilepsy could be amended to include a role for epilepsy surgery in appropriately selected cases.

References

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2. Walczak TS, et al: Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases. Neurology 1990; 40: 413-18.

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4. Wiebe S, et al: A randomized, controlled trial of surgery for temporal lobe epilepsy. N Engl J Med 2001; 345: 311-18.

5. Spencer SS: Long-term outcome after epilepsy surgery. Epilepsia 1996; 37: 807-13.

6. Markand ON, Salanova V, Whelihan E, Emsley CL: Health-related quality of life outcome in medically refractory epilepsy treated with anterior temporal lobectomy. Epilepsia 2000; 41: 749-59.

7. Kellet MW, Smith DF, Baker GA, Chadwick DW: Quality of life after epilepsy surgery. J Neurol Neurosurg Psychiatry 1997; 63: 52-8.

8. Engel J Jr: Outcome with respect to epileptic seizures. In: Surgical Treatment of the Epilepsies, pp 553-71. Edited by Engel J Jr. New York, NY, Raven Press, 1987.

9. Standards of Medical Fitness, Army Regulation 40-501. Washington, DC, Department of the Army, 1989.

10. Gunderson CH: Administrative management of the soldier with seizures. Milit Med 1991; 156: 328-30.

11. Medical Examinations and Standards, Air Force Instruction 48-123. Washington, DC, Department of the Air Force, 2000.

12. Maganti RK, Rutecki PA, Bell BD, et al: Epilepsy surgery outcome among US veterans. Epilepsy Behav 2003; 4: 723-8.

13. Exceptional Family Member Program, Army Regulation 608-75. Washington, DC, Department of the Army, 1996.

14. Radhakrishnan K, et al: Predictors of outcome of anterior temporal lobectomy for Intractable epilepsy: a multivariate study. Neurology 1998: 51: 465-71.

15. Berkovic SF, et al: Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis. Neurology 1995; 45: 1358-63.

16. Garcia PA, Laxer KD, Barbara NM, Dillon WP: Prognostic value of qualitative MRI hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures. Epilepsia 1994; 35: 520-4.

17. Salanova V, Markand O, Worth R: Longitudinal follow-up in 145 patients with medically refractory temporal lobe epilepsy treated surgically between 1984 and 1995. Epilepsia 1999; 40: 1417-23.

Guarantor: MAJ Jay C. Erickson, MC USA

Contributors: MAJ Jay C. Erickson, MC USA*; Richard G. Ellenbogen, MD[dagger]; Kaveh Khajevi, MD; LCDR Lisa Mulligan, MC USN; Gwendolyn C. Ford, MD*; COL Bahman Jabbari, MC USA (Ret.)[double dagger]

Departments of Neurology and Neurosurgery, Walter Reed Army Medical Center, Washington, DC 20307, and Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

* Current address: Neurology Service, Madigan Army Medical Center, Tacoma, WA 98431.

[dagger] Current address: Department of Neurosurgery, University of Washington, Seattle, WA 98195.

[double dagger] Current address: Department of Neurology, Yale University, New Haven, CT 06520.

Presented at the American Epilepsy Society Meeting, December 11, 2002, Seattle, WA.

The views and opinions contained herein are the private ones of the authors and are not to be construed as representing the views of the Department of Defense, the Department of the Army, or Uniformed Services University of the Health Sciences.

This manuscript was received for review in February 2004. The revised manuscript was accepted for publication in April 2004.

Reprint & Copyright © by Association of Military Surgeons of U.S., 2005.

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