Posttraumatic Epilepsy in Operation Enduring Freedom/Operation Iraqi Freedom Veterans

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1 MILITARY MEDICINE, 179, 5:492, 2014 Posttraumatic Epilepsy in Operation Enduring Freedom/Operation Iraqi Freedom Veterans Leo L. K. Chen, MD* ; Christine B. Baca, MD, MSHS ; Jessica Choe, MD ; James W. Chen, MD, PhD ; Miriam E. Ayad, MPH ; Eric M. Cheng, MD, MS ABSTRACT Penetrating traumatic brain injury (TBI) is a well-established risk factor for post-traumatic epilepsy (PTE). However, many veterans in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) who suffer from TBI do so from blast injury, and its consequences are not fully known. Two neurologists performed a chart review to describe patterns of injury and health care among all 16 OEF/OIF veterans at the VA Greater Los Angeles Healthcare System who were assigned an outpatient diagnosis of both epilepsy and TBI in All Veterans were male, and the mean age was 30 years. Blast exposure was the most common mechanism of TBI (81%). Although all Veterans were assigned a diagnosis code of seizures, the diagnosis of PTE was clinically confirmed in only 3 veterans. On the other hand, the diagnosis of post-traumatic stress disorder was confirmed in 81% of the sample and a diagnosis of nonepileptic seizures was suspected in 44% of the sample. Researchers who study PTE among the OEF/OIF population using administrative data also should perform chart reviews to account for the prevalence of psychogenic nonepileptic seizures. INTRODUCTION Moderate to severe traumatic brain injury (TBI) is a wellestablished risk factor for post-traumatic epilepsy (PTE). 1 5 However, the TBI suffered by soldiers in the recent Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) in Iraq and Afghanistan is different from prior wars. Up to 20% of the 1.6 million U.S. soldiers deployed in these operations has suffered a TBI. 6 Soldiers are now more likely to survive from a TBI because of improvements in body armor and frontline surgical stabilization. 7 In addition, the mechanism of TBI in the more recent deployments is now more likely to be nonpenetrating blast injury instead of penetrating TBI as studied in previous conflicts. 6,8,9 Improvised explosive devices (IEDs) account for the majority of the blast injuries. 10 The risk of PTE is directly associated with the severity of the TBI. Most blast-related TBI would be classified as mild severity, and studies have not shown an increase in PTE among patients with TBI of mild severity. However, blastrelated, mild severity TBI may have different sequelae from *Department of Neurology, Kaiser Permanente Foundation Hospital, 2025 Morse Avenue Sacramento, CA Department of Neurology, UC Davis Health System, 4860 Y Street Sacramento, CA Department of Neurology, University of California, San Diego, 200 West Arbor Drive, San Diego, CA Department of Neurology, VA Greater Los Angeles Healthcare System, Wilshire Boulevard ML 127, Los Angeles, CA kdepartment of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, C167 RNRC, Los Angeles, CA This article was presented at the 65th American Epilepsy Society Annual Meeting, Baltimore, MD, December 6, The views expressed in this article are those of the authors and do not necessarily represent the position or policy of the Department of Veterans Affairs or the U.S. Government. doi: /MILMED-D mild-severity TBI experienced in the civilian population who were enrolled in well-known epidemiology studies. We performed a chart review to determine the frequency of PTE and patterns of clinical characteristics and health care utilization among OEF/OIF veterans with TBI in one VA health care system. MATERIALS AND METHODS Setting and Sample This study was carried out at VA Greater Los Angeles Healthcare System, which comprises one hospital and 14 outpatient clinics. In 2008, there were over 1,073,560 visits in this system and there were 77,642 unique patients receiving care during this year. The inclusion criteria of our study was all OEF/OIF veterans with an outpatient International Classification of Disease-9 diagnosis codes of both seizures and TBI assigned during the 2-year period of October 1, 2007 to September 30, 2009 (Fig. 1). We reviewed the medical literature to find a consensus set of codes. For epilepsy, we used codes of epilepsy (345) or convulsions (780.3). 11 ForTBI, we used codes of head trauma (339.2: post-traumatic headache; : skull or facial bone fracture; : intracranial injury or open wound of head; 907: late-effect, intracranial injury; 959: unspecified face and neck injury) Medical Record Review Two neurologists (L. Chen, J. Choe) reviewed the VA medical record, starting from the start of the electronic health record in 1998 to April 2011 to confirm the diagnoses of TBI and seizures. We defined seizures to encompass both epileptic seizures and psychogenic nonepileptic seizures (PNES). The chart reviewers did not form their own clinical interpretation of the medical record, but instead, 492

2 FIGURE 1. Inclusion and exclusion criteria used to identify study sample. they abstracted the literal assessments documented by the treating clinicians. The neurologists then abstracted demographic and clinical data on these veterans, including neuroimaging, electroencephalograms (EEG), the use of antiepileptic drugs (AED), and the presence of comorbidities. Starting in April 2007, all newly enrolled OEF/OIF Veterans complete a four-question TBI screener. 7,16,17 If Veterans screen positive, they are asked to make a follow-up appointment with a health professional to complete the 25-item TBI Comprehensive Evaluation. That survey has items about injury etiology; exposure to primary, secondary, tertiary, and quaternary blast; distance from blast; duration of disorientation, confusion, amnesia, or unconsciousness; neurobehavioral symptoms; and quality of life. 18 There are no questions to assess the presence of seizures. When the neurologists were able to find the responses of the screener and the TBI Comprehensive Evaluation in the medical record, they abstracted the information about TBI. However, even when the responses were available, the neurologists also reviewed the clinical notes for additional information. TBI severity was defined according to definitions from the Department of Veterans Affairs and Department of Defense in Mild TBI was defined as normal imaging and loss of consciousness (LOC) less than 30 minutes, alteration of consciousness (AOC) less than 24 hours, or post-traumatic amnesia (PTA) less than 1 day. Moderate TBI was defined as LOC greater than 30 minutes but less than 24 hours, AOC greater than 24 hours, or PTA from 1 to 7 days. Severe TBI was defined as LOC greater than 24 hours, AOC greater than 24 hours, or PTA greater than 7 days. The data abstracted by the two neurologists were compared. Disagreement was resolved by a further review of the medical charts. The analysis consisted of descriptive statistics. This research was approved by the Institutional Review Board of the VA Greater Los Angeles, and a waiver of consent was granted. 493

3 RESULTS A query of the local administrative database identified 235 veterans with diagnosis codes for epilepsy and head trauma. 216 veterans served in theaters other than OEF/OIF, such as World War II, Korea, or Vietnam. Of the 19 OEF/OIF veterans, the chart reviewers were unable to find any documentation of either TBI or seizures for 3 veterans, thus a chart review was completed in only 16 veterans. The demographics of the sample are shown in Table I. All were male, and the mean age was 30.3 years. The clinical characteristics are shown in Table II. In our sample, 9 veterans (56%) completed the comprehensive TBI evaluation. The most common mechanism of TBI was blast injury as documented in 13 (81%) veterans. Among those with blast injuries, IEDs were identified as the cause in 10 (77%) veterans. The severity of TBI was about equally divided among mild (38%), severe (31%), and unknown (31%) categories. The diagnostic workup for epilepsy is also shown in Table II. Among the 12 veterans who underwent a scalp EEG, 7 (58%) were reported as normal, 3 (25%) with epileptiform activity, and 2 (17%) with nonspecific abnormalities. Among the 4 veterans who underwent inpatient continuous video EEG monitoring, 2 veterans had confirmed nonepileptic seizures, and the other 2 veterans did not have any seizures captured during their admission, and testing was thus, nondiagnostic. There were 14 veterans who underwent brain imaging. Among this group, 9 (64%) were reported as normal. Only TABLE I. Demographic Characteristics of OIE/OEF Veterans With TBI and Post-traumatic Seizures N = 16 (%) Male 16 (100) Age, Years, Mean (SD), Range (At Time of Chart Review) Years, Mean 30.3 Race White 12 (75) Asian 1 (6) Black 1 (6) Unknown 2 (13) Education ³College (Ex. Bachelor s Degree) 2 (13) Some college (Ex. 4Year College, 6 (38) Associate Degree or Technical Degree) ³High School (Includes General 6 (38) Educational Development) Unknown 2 (13) Employment Status Employed (Full or Part-Time) 3 (19) Unemployed 9 (56) Student (Full or Part-Time) 3 (19) Unknown 1 (6) Marital Status Married 5 (31) Divorced 2 (13) Living With Domestic Partner 2 (13) Never Married 6 (38) Unknown 1 (6) 3 veterans had findings (either metal fragments or hemorrhage) that have been associated with increased risk of developing PTE, whereas the remaining 2 veterans had nonspecific findings. The abstractors identified only 3 veterans (cases 2, 6, and 13 in Table II) for whom treating clinicians documented a working diagnosis of epilepsy. Case no. 2 suffered from a bullet wound, resulting in metal fragments found on neuroimaging. Even though it was a penetrating injury, we classified the TBI as unknown severity because we did not have information on duration of LOC, AOC, and PTA. He had epileptiform activity on an EEG. He was treated with an AED and has been seizure-free for the past year at the last available clinic visit. Case no. 6 had unknown severity of TBI because of blast. We were unable to find results of neuroimaging, but he had a normal EEG. He was treated on an AED and has been seizure-free for the past year at the last available clinic visit. Case no. 13 had mild TBI because of blast. Although magnetic resonance imaging (MRI) of the brain was normal, the EEG showed epileptiform activity. At the last clinic visit, he was not taking an AED and has been seizure-free for the past year at the last available clinic visit. Although the diagnosis of PTE was clinically confirmed in only 3 veterans, the diagnosis of PNES was suspected in 7 (44%) other veterans. Psychiatric comorbidities were common. Post-traumatic stress disorder (PTSD) was reported in 13 (81%) veterans, followed by depression in 7 (44%) veterans and anxiety disorder in 4 (25%) veterans. Although 10 (63%) veterans were prescribed AEDs, only 5 were prescribed AEDs exclusively for epilepsy. Indications for AED other than epilepsy include management of migraine, impulsivity, mood, and pain. DISCUSSION In our study, the majority of OEF/OIF veterans with a diagnosis code of TBI suffered blast injuries, and the cause of TBI was usually due to IEDs. However, we had difficulty confirming the diagnosis of epilepsy. Instead, we found documentation about the suspicion of PNES in about half of the charts that we reviewed. Determining whether episodic alterations of memory or concentration are a manifestation of epileptic seizures, nonepileptic seizures, TBI, or PTSD can be challenging given their overlapping symptomatology and frequent comorbid presentation. 19,20 Because TBI raises the risk of PTE, PNES, and PTSD, it may be quite difficult to establish a definitive diagnosis Studies have reported that PNES was diagnosed between 24% and 33% of the time in cohorts with head trauma being evaluated at epilepsy centers However, we stress that even if Veterans are diagnosed with PNES, they still have a high level of medical needs. Although such Veterans may not benefit from medical treatments for epilepsy, they would benefit from being managed by clinicians familiar with PNES. 494

4 TABLE II. Cohort of OEF/OIF Veterans With Diagnosis Codes of Seizures and Head Trauma ID TBI Severity and Mechanism Seizure (Event) Frequency Neuroimaging EEG Results Nonepileptic Events Suspected Ever Treated with AED 1 Severe; Blunt Trauma Seizure-Free a MRI = Metal Fragment, None No No No Focal Encephalomalacia CT = Hematoma, Skull Fracture 2 Unknown; Bullet Seizure-Free CT = Metal fragment, Atrophy, Epileptiform No Yes Yes Focal Encephalomalacia 3 Unknown; Blast >Daily MRI = Normal Normal No No Yes 4 Mild; Blast/MVA/Fall N/A MRI = Normal Normal No Yes Yes 5 Mild; Blast/MVA Weekly Monthly MRI = Normal Normal; No Yes Yes Video: No Events Captured 6 Unknown; Blast Seizure Event N/A Normal; No Yes Yes Video: No Events Captured 7 Mild; Blast/MVA <Yearly MRI = Normal N/A No No Yes 8 Severe; Blast/MVA Seizure-Free MRI = Normal N/A Yes No Yes 9 Severe; Blast Seizure-Free MRI = Atrophy (L Temporal) Normal Yes Yes Yes CT = Hemorrhage (L Temporal) 10 Unknown; Blast/MVA/Fall Daily Weekly MRI = Normal Normal Yes No Yes 11 Severe; MVA Daily Weekly MRI = Nonspecific Subcortical Hypointensity Consistent With Diffuse Axonal Injury CT = normal 12 Unknown; Blast N/A MRI = Normal CT = normal Epileptiform Video: Nonepilepiform Events PTSD Yes Yes Yes Nonspecific Yes No Yes 13 Mild; Blast/MVA/Fall Seizure-Free MRI = Normal Epileptiform No Yes No 14 Mild; Blast N/A MRI = Normal Nonspecific; Yes Yes Yes Video: Nonepileptic Events 15 Mild; Blast Seizure-Free MRI = Normal Normal Yes No Yes 16 Severe; Blast Weekly Monthly N/A N/A No No No Mild TBI = normal imaging, 0 to 30 minutes LOC, momentary 24 hours AOC, or 0 to 1 day PTA; Moderate TBI = normal or abnormal imaging, 30 minutes 24 hours LOC, momentary 24 hours AOC, or > 1 to 7 days PTA; Severe TBI = normal or abnormal imaging, > 24 hours LOC, > 24 hours LOC, > 24 hours AOC, or > 7 days PTA. CT = computed tomography; MVA = motor vehicle accident. a Seizure-free = no seizures in >1 year. Given the large number of OEF/OIF Veterans who have reported TBI, the use of administrative databases may be the only option for tracking the development of PTE. The accuracy of codes for epilepsy is quite high and better than most other neurological conditions. 11,28 When analyzing PTE using administrative datasets, one may think that the barrier is accurately identifying patients with TBI. We acknowledge that there are fewer validation studies of TBI, and that the accuracy is lower. 14,28 In our results, we were a bit surprised that we had a greater problem in confirming epilepsy than TBI. We speculate that this is because the symptoms of epilepsy and PNES overlap with the sequela of TBI. We recommend adding a single question about seizures to the 25-item TBI Comprehensive Evaluation so that patients can be identified for further clinical evaluation or research. A previous study determined that a single-item question had a good combination of sensitivity, specificity, and positive predictive value. 29 Adapting that question to patients with TBI would be: Since your head trauma, have you ever had, or has anyone ever told you that you had a seizure, convulsion, fit, or spell under any circumstance? Our study has several limitations. First, the documentation in the medical chart may be incomplete for a variety of reasons. The Veterans Administration does not contain the clinical notes written at the onset of TBI. Therefore, some key clinical information may be unavailable to our chart abstractors. The history questions in the TBI Comprehensive Evaluation were extremely valuable, but not all Veterans completed the TBI Comprehensive Evaluation, even after being asked to do so. Some veterans may be receiving neurological care outside of the VA system, leading to an underestimation of workup and diagnoses. Second, clinicians may not have documented their diagnostic impression if they were not certain of the diagnosis. In such cases, the chart reviewers would not be able to abstract the thought process of the treating clinician. Finally, the sample originates from just one VA medical center. Recognizing the need to improve the care of epilepsy in the Veterans Administration, the Veterans Mental Health and Other Care Improvements Act of 2008 (PL ) established the VA Epilepsy Centers of Excellence. Part of this mandate is to study the risk of epilepsy because of TBI, particularly those from blast-related, closed-head injuries. 495

5 CONCLUSION In conclusion, we found documentation of a definitive diagnosis of PTE in only a small proportion of OEF/OIF veterans with diagnosis codes of TBI and seizures. We recommend that researchers who study PTE among the OEF/OIF population using administrative data also perform chart reviews to account for the prevalence of PNES. ACKNOWLEDGMENTS The study was supported by the VA Epilepsy Center of Excellence at VA Los Angeles. Dr. Cheng was supported by Career Development Award from NIH/NINDS (K23NS058571). REFERENCES 1. Lowenstein DH: Epilepsy after head injury: an overview. Epilepsia 2009; 50 (Suppl 2): Annegers JF, Grabow JD, Groover RV, et al: Seizures after head trauma: a population study. Neurology 1980; 30(7 Pt 1): Annegers JF, Hauser WA, Coan SP, Rocca WA: A population-based study of seizures after traumatic brain injuries. 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