Psychiatric co-morbidity of drug-resistant epilepsy in Veterans.

OBJECTIVE: Psychiatric conditions are frequently co-morbid in epilepsy and studies examining Veterans with epilepsy suggest this population may present with unique psychiatric and clinical features Drug-resistant epilepsy (DRE) may confer a greater risk of psychiatric dysfunction; however, there is a paucity of literature documenting this. To expand our clinical understanding of Veterans with DRE, we assessed a comprehensive Veterans Health Administration (VHA)-wide sample, describing psychiatric conditions, medications, and healthcare utilization. METHODS: Psychiatric and hospitalization data were collected on 52,579 Veterans enrolled in VHA healthcare between FY2014-2ndQtr.FY2020 from the VHA Corporate Data Warehouse administrative data. Data examined include psychiatric diagnosis, psychotropic medication use, and utilization of hospital services. RESULTS: At least one psychiatric diagnosis was present in 70.2% of patients, while 49.8% had two or more diagnoses. Depression (51.7%), posttraumatic stress disorder (PTSD) (38.8%), and anxiety (38.0%) represented the most common psychiatric co-morbidities. Psychiatric medication use was present in 73.3%. Emergency room (ER) visits were highest in those with suicidality (mean 14.9 visits), followed by bipolar disorder (10.3), and schizophrenia (12.1). Psychiatric-related hospitalizations were highest for schizophrenia (mean 2.5 admissions) and bipolar disorder (2.3). Females had more psychiatric diagnoses (2.4 vs. 1.6, p < 0.001), psychiatric medications (3.4 vs. 2.3, p < 0.001), and ER utilization than males (6.9 vs. 5.5, p < 0.001). SIGNIFICANCE: A substantial psychiatric burden exists among Veterans with DRE. Compared to prior epilepsy literature, results suggest that Veterans with DRE evidence more prevalent psychiatric comorbidity, emergency care usage, and inpatient psychiatric admissions. Females were especially impacted, with greater rates of psychiatric conditions and treatment. Considering the relationship of psychiatric comorbidities in epilepsy with psychosocial functioning and quality of life, our findings highlight the need for screening and provision of services for those with DRE.

The prevalence of epilepsy and association with traumatic brain injury in veterans of the Afghanistan and Iraq wars.

OBJECTIVE: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. DESIGN: Cross-sectional observational study. PARTICIPANTS: A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. MAIN OUTCOME MEASURES: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. RESULTS: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). CONCLUSIONS: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans.

Utilization of epilepsy care among Women Veterans: A population-based study.

OBJECTIVE: Higher healthcare utilization in epilepsy correlates with better clinical and quality of life outcomes. Women Veterans with epilepsy (WVE) have unique characteristics that may affect access and utilization of care. This study investigates epilepsy care in WVE, with respect to utilization of outpatient, inpatient, and emergency room care. METHODS: Data were collected from 58,525 Veterans with epilepsy using the Veterans Health Administration (VHA) Corporate Data Warehouse administrative data. Overall, 8.5% of the sample were women (n = 4983). Neurology visits, comprehensive epilepsy care, neuroimaging, ASM prescription and hospital and emergency care were analyzed, and comparisons were made with men Veterans with epilepsy to identify gender differences. RESULTS: Compared to men, a greater proportion of WVE utilized services including neurology (73.8% vs. 62.0%), comprehensive epilepsy care (16.1% vs. 11.7%), epilepsy monitoring unit evaluation (EMU; 6.1% vs. 2.9%), neuroimaging (CT: 39.1% vs. 36.6%; MRI: 43.7% vs. 32.5%), and electroencephalograms: (EEG: 36.5% vs. 29.1%). WVE also evidenced higher percentages of seizure-related emergency room care usage vs. men (15.2 vs. 12.6) and hospitalizations (12.3 vs. 10.0) and were prescribed a greater number of ASMs (average:2.3 vs. 1.9). Valproate was prescribed to 17.6% of WVE, despite potential teratogenic concerns. SIGNIFICANCE: WVE have greater utilization of epilepsy care within the VHA system compared to men, which could lead to better epilepsy management and quality of life. However, higher rates of emergency care, hospitalizations, and concurrent ASMs among WVE highlight the clinical complexity and raise concern for potentially comorbid conditions including psychogenic non-epileptic seizures.

Role of Deployment History on the Association Between Epilepsy and Traumatic Brain Injury in Post-9/11 Era US Veterans.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a well-established epilepsy risk factor and is common among service members. Deployment-related TBI, where combat/blast may be more common, may have different outcomes than nondeployment-related TBI. This work examined associations of all TBI exposures (not just combat), and epilepsy, while adjusting for comorbidities associated with epilepsy, among veterans by deployment status. METHODS: The cohort included post-9/11 veterans with ≥2 years of care in both Veterans Health Administration and Defense Health Agency systems. We identified epilepsy using ICD-9/10-CM codes, antiseizure medication, and service-connected disability for epilepsy. We conducted a logistic regression model with interaction terms for conditions by deployment history that adjusted for demographics and military characteristics. RESULTS: The cohort (n = 938,890) included post-9/11 veterans of whom 27,436 (2.92%) had epilepsy. Most veterans had a history of deployment (70.64%), referred to as "deployed." Epilepsy was more common among veterans who were never deployed ("nondeployed") (3.85% vs 2.54%). Deployed veterans were more likely to have had TBI, compared with the nondeployed veterans (33.94% vs 14.24%), but nondeployed veterans with moderate/severe TBI had higher odds of epilepsy compared with deployed veterans (adjusted odds ratio [aOR] 2.92, 95% CI 2.68-3.17 vs aOR 2.01, 95% CI 1.91-2.11). Penetrating TBI had higher odds of epilepsy among the deployed veterans (aOR 5.33, 95% CI 4.89-5.81), whereas the odds of epilepsy for mild TBI did not significantly differ by deployment status. Although most neurologic conditions were more prevalent among the nondeployed veterans, they were often associated with higher odds of epilepsy in the deployed veterans. DISCUSSION: Deployment history had a significant differential impact on epilepsy predictors. As expected, penetrating TBI had a greater epilepsy impact among deployed veterans perhaps due to combat/blast. Some epilepsy predictors (moderate/severe TBI, multiple sclerosis, and Parkinson disease) had a stronger association in the nondeployed veterans suggesting a potential healthy warrior effect in which such conditions preclude deployment. Other neurologic conditions (e.g., brain tumor, Alzheimer disease/frontotemporal dementia) had a greater epilepsy impact in the deployed veterans. This may be attributable to deployment-related exposures (combat injury, occupational exposures). A better understanding of deployment effects is critical to provide targeted epilepsy prevention in veterans and military service members.

Differentiation of Epileptic and Psychogenic Nonepileptic Seizures Using Single-Channel Surface Electromyography.

PURPOSE: Epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) are difficult to differentiate when based on a patient's self-reported symptoms. This study proposes review of objective data captured by a surface electromyography (sEMG) wearable device for classification of events as ES or PNES. This may help clinicians accurately identify ES and PNES. METHODS: Seventy-one subjects were prospectively enrolled across epilepsy monitoring units at VA Epilepsy Centers of Excellence. Subjects were concomitantly monitored using video EEG and a wearable sEMG epilepsy monitor, the Sensing Portable sEmg Analysis Characterization (SPEAC) System. Three epileptologists independently classified ES and PNES that contained upper extremity motor activity based on video EEG. The sEMG data from those events were automatically processed to provide a seizure score for event classification. After brief training (60 minutes), the sEMG data were reviewed by a separate group of four epileptologists to independently classify events as ES or PNES. RESULTS: According to video EEG review, 17 subjects experienced 34 events (15 ES and 19 PNES with upper extremity motor activity). The automated process correctly classified 87% of ES (positive predictive value = 88%, negative predictive value = 76%) and 79% of PNES, and the expert reviewers correctly classified 77% of ES (positive predictive value = 94%, negative predictive value = 84%) and 96% of PNES. The automated process and the expert reviewers correctly classified 100% of tonic-clonic seizures as ES, and 71 and 50%, respectively, of non-tonic-clonic ES. CONCLUSIONS: Automated and expert review, particularly in combination, of sEMG captured by a wearable seizure monitor (SPEAC System) may be able to differentiate ES (especially tonic-clonic) and PNES with upper extremity motor activity.

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee.

PURPOSE: Established tonic-clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. METHODS: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process. RESULTS: No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study). CONCLUSIONS: Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

"Chance Takers Are Accident Makers": Are Patients With Epilepsy Really Taking a Chance When They Drive?

This review compiles scientific data about the real dangers faced by people with epilepsy (PWE) who drive. Those include risks of motor vehicle accidents (MVA) in PWE as compared with controls (individuals without epilepsy) and as compared with persons with other medical conditions that impact fitness to drive. Data regarding Accident rates as related to seizure free intervals (SFI), single vs. multiple seizure events, and/or antiseizure drug (ASD) taper and reintroduction are discussed. Variation in state, national, and international laws and guidance for non-commercial and commercial drivers is highlighted, along with some related reasons for driving restrictions. The review concludes by emphasizing the importance of physicians educating patients about local driving laws and about risks of ASD non-adherence. The need for a broader, multi-stakeholder re-examination of driving regulations for PWE is noted.

Comparisons of the mortality and clinical presentations of status epilepticus in private practice community and university hospital settings in Richmond, Virginia.

We prospectively compared the clinical course of 119 patients treated for status epilepticus (SE) in private practice community hospitals and 344 SE patients treated in the VCU university hospitals in Richmond, Virginia USA over a 2-year period to test the hypothesis that SE presents with the same mortality and clinical patterns in both clinical settings. Of the patients reviewed, the major etiologies for SE were cerebrovascular disease, decreased anti-epileptic drug levels in epileptic patients, anoxia-hypoxia, and remote symptomatic. The other etiologies included were alcohol related, trauma, central nervous system infections, tumors, systemic infection, metabolic disorders, idiopathic, and hemorrhage. These observations provide the first direct prospective comparison of SE present in university and private practice community hospital settings in the same geographic area. Mortality was the highest in the elderly population while the pediatric population had low mortality in both clinical settings. Etiology risk factors for outcome were similar for both the populations. The data also suggest that the higher degree of illness severity in university hospitals may be associated with a higher incidence of SE, but not with mortality or a different clinical presentation of the condition. The results of this study demonstrate that SE has the same mortality and is present in an essentially identical manner in university and private practice community hospitals and underscores the fact that mortality in SE is not just associated with tertiary care hospitals and the importance of recognizing the severity of SE in the private practice setting.

Epidemiology and outcomes of status epilepticus in the elderly.

Status epilepticus (SE) is a serious condition of prolonged or repetitive seizures. The annual incidence (86/100,000) of SE in the elderly who are aged 60 and greater is almost twice that of the general population and is even higher in those who are 70 years and older. Either acute or remote symptomatic stroke causes approximately 60% of SE seen in the elderly. SE is associated with a high mortality in the elderly (38%), with a rate approaching 50% in patients older than 80 years of age. Etiology is a strong determinant of mortality in the elderly: mortality approaches 100% in patients with anoxia and 30% in patients with either metabolic disorders, hemorrhages, tumors, or systemic infections. Mortality is almost three times higher in SE associated with acute ischemic stroke than in stroke alone, indicating synergistic effects. Duration of SE is also a factor in mortality. Treatment should be initiated for any convulsive seizure that lasts at least 10 min or is repetitive. An electroencephalogram (EEG) should be promptly obtained so that a diagnosis can be made without delay. Because older patients have a greater likelihood of nondiagnostic findings on routine EEGs, prolonged EEG recordings and inpatient video-EEG monitoring significantly increase the rate of establishing a definitive diagnosis. Nonconvulsive status epilepticus in the elderly is especially difficult to diagnose and should be evaluated with an EEG. Treatment of SE is complicated by altered pharmacokinetics in the elderly. Initial treatments, usually the administration of an intravenous benzodiazepine, have overall success rates of 55% for overt convulsive SE and 14.9% for subtle SE. For refractory SE, little is gained by using additional standard drugs, and general anesthesia with continuous EEG monitoring is recommended.