Total Impact of Epilepsy: Biological, Psychological, Social, and Economic Aspects
David Blum, MD
Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona
The impact of epilepsy upon those who suffer from this disorder extends far beyond the injury that seizures themselves can cause. The unpredictability of seizures imposes severe restrictions on lifestyle and can inhibit patients’ social interactions. Medical and surgical treatments are associated with numerous adverse side effects. Given the high direct and indirect costs of epilepsy, patients may best be treated at tertiary centers where specialized services are available.
Key Words: epilepsy, seizures
Epilepsy can adversely affect the quality of life of many who suffer from this disorder. This article reviews important biological, psychological, social, and economic consequences of epilepsy and how they affect the lives of patients.
Impact of Seizures
The most obvious impact of epilepsy is the direct result of seizures themselves. Seizures can produce medical injury or injury from unfavorable interactions with the environment during the seizure. Medical injury from seizures is relatively rare except in cases of status epilepticus. Aspiration and hypoxia are the most common major complications. However, aspiration pneumonia is actually quite rare when convulsive seizures occur in an outpatient setting and is seen more often in hospitalized patients who have seizures and are subsequently intubated. The chief cardiac complication is arrhythmia. Each year, sudden unexplained death in epilepsy occurs in 0.2% of individuals with poorly controlled epilepsy.8 The cause is uncertain, but evidence supports neurogenic pulmonary edema or cardiac arrhythmia as likely causes.
An unanswered question is whether seizures themselves cause brain damage. In animals, repeated subthreshold electrical stimulation of the limbic system ultimately leads to the development of a chronic focus of spontaneous seizures. Histologically, this focus is marked by a loss of neurons in the hippocampal formation of the temporal lobe. This cell loss is associated with a decline in memory function.
Human temporal lobe epilepsy is associated with the same histological pattern of hippocampal cell loss and a similar memory deficit. There has only been one long-term longitudinal follow-up study of memory function in individuals with temporal lobe epilepsy.15 Patients who did not have epilepsy surgery and who continued to have seizures showed a decline in memory function over a 10-year follow-up. Other long-term follow-up studies of decline in mental function in human epilepsy have been marred by the inclusion of all seizure types, by studying broad measures of intellectual function such as the intelligent quotient (IQ) rather than measures specific to the function of an area involved in the seizure focus (e.g., memory in temporal lobe epilepsy), by inadequate follow-up intervals, and by the sickest persons dropping out of the sample.
Another method of determining whether seizures are associated with damage to the hippocampus would be long-term high-resolution imaging of the structure to evaluate changes in its volume over time. This study would have to begin in patients with newly diagnosed temporal lobe epilepsy and continue with longitudinal follow-up. Typically, such patients are not referred early in their clinical course to centers with access to this form of brain imaging, and adequate studies have not been done.
Another effect of repeated temporal lobe seizures may be a chronic change in personality, known as the “Geschwind syndrome.”2,21 Some patients with longstanding temporal lobe epilepsy develop personality changes including loss of spontaneity, hyposexuality, “stickiness” (which refers to a tendency to focus overbearingly on a single topic or an inability to terminate a conversation), hypergraphia, and excessive concern for broad moral implications of daily events. Alterations in religious belief also accompany this syndrome, and hyperreligiosity and idiosyncratic personal belief systems can gradually develop. Such patients often experience tremendous social isolation.
Most injuries related to seizures occur because of unfortunate interactions between the seizing patient and the environment. Patients can fall and strike their head or fracture bones.17 Burns are common in persons with epilepsy18 and can arise in a number of ways. Complex partial seizures can include automatisms (i.e., senseless repetitive movements). A patient holding a cigarette at the start of a seizure might rub the burning end into his or her arm without being aware of the pain. In the kitchen, hot objects may be dropped or a hand or arm placed in the fire. In hot climates, patients have developed third-degree burns by lying senseless in a postictal state on hot pavement. During complex partial or tonic clonic seizures, the patient is not reactive to the environment and injuries can occur during driving, climbing ladders, or operating power tools. Patients have drowned while swimming or bathing in tubs.
Impact of Treatment
The treatment of seizure disorders is aimed at preventing seizures. For many patients, the side effects of treatment have an impact as great as the impact of the seizures themselves. Side effects from medication plague patients with epilepsy on a daily basis. The most important medication side effects are changes in cognitive function. Anticonvulsants routinely cause patients to feel sedated or to feel that their thinking is “foggy.” Almost all seizure medicines share this side effect, which is a leading reason for patients failing to comply with their regimen of medications.
Some seizure medications are more problematic than others. Depression and suicide attempts are common among patients on phenobarbital or primidone. Topiramate often leads to mental blunting, word-finding difficulties, and irritability. In as many as 5% of patients, vigabatrin is associated with depression, psychosis, or both.
Other problems are unique to individual medications (Table 1). Side effects can also be related to childbearing. Some seizure medications can lead to failure of birth control medications and unplanned pregnancy. Most major seizure medications are associated with “fetal anticonvulsant syndrome” characterized by a constellation of minor malformations. Valproate and carbamazepine are associated with about a 1% risk of neural tube defects. The use of barbiturate medications during pregnancy may be associated with a 5- to 10-point decrease in the IQ of children.16
The surgical treatment of epilepsy also can affect patients adversely. The most important unwanted effects of temporal lobe epilepsy surgery are memory difficulties, which can be severe in as many as 1 to 2% of patients. Other problems include visual field loss and other focal neurological deficits, all of which seem to be less than 0.5% in major series. Depression follows a small fraction of temporal lobectomies (the number is uncertain but may be in the range of 1 in 20). Postoperative psychosis is distinctly uncommon.22 The major risks of extratemporal epilepsy surgery relate to focal deficits arising from the resection and can usually be avoided by proper cortical mapping. Perioperative complications including infection, hemorrhage, stroke, and death are typically 0.1 to 0.2%, which is less than the risk of sudden unexplained death from epilepsy in this population. Despite these risks, epilepsy surgery remains the most effective treatment available, especially for temporal lobe epilepsy.
Impact of the Unpredictability of Seizures
The greatest impact of epilepsy actually relates to patients not knowing when a seizure will occur. For example, patients who have only one seizure a month are “out of commission” only 1 to 2 minutes during the seizure and perhaps 30 minutes for postictal recovery. Such patients are therefore affected by their seizure less than 0.1% of the time. They do not, however, know when a seizure will occur and so are prevented from driving and participating in many other activities. Driving restrictions vary by states, but most states now require patients be free of seizures 3 months to 1 year before they can drive. Commercial drivers and large truck drivers may lose their license for life. The Federal Aviation Administration will not allow anyone who has had a seizure at anytime since childhood to fly. These limitations restrict liberty and make earning a living difficult.
Although a person with only one seizure a month is “disabled” only a small fraction of the time, such patients may have a very difficult time keeping a job. Seizures that occur while waiting for or riding a bus can cause individuals to be late for work and lead to their dismissal. The confused behavior typical of temporal lobe complex partial seizures can be disturbing to coworkers and likewise can lead to dismissal. For example, a 41-year-old male working in a hardware store had a complex partial seizure while stocking spray paint cans on a shelf. During the seizure he began spraying red paint, absentmindedly walking the length of the aisle and painting the entire stock of the store red. He was dismissed. In another instance, a 30-year-old receptionist had a complex partial seizure while answering the phone. She mumbled incoherently to the client and hung up. The client complained about her behavior on the phone, and she was dismissed.
More dramatic seizures at work (e.g., partial seizures of frontal lobe origin, tonic-clonic seizures) are distressing to watch and upsetting to others in the workplace. After a seizure at work, individuals with epilepsy have often found themselves dismissed, moved to a remote office, or isolated. Numerous surveys have shown high rates of unemployment or underemployment in persons with epilepsy.6 Patients may feel encouraged to lie to prospective employers because truthfulness undermines their chances of being hired.14
Completing school can also be a challenge for persons with epilepsy. Cognitive deficits related to seizures and to medications can make mastery of material difficult. Seizures can occur during lectures. In particular, absence epilepsy tends to be noticed at school by teachers as “spacing out.” In this case, good seizure control leads to improved school performance. Many people with epilepsy find that seizures occur more often at times of stress, which for students means during examinations. Late-night study sessions can lead to sleep deprivation, increasing the tendency toward seizures. Many school sports teams have restrictions that prohibit students with epilepsy from playing. In any event, a student who has a seizure at a critical point in a competitive game will not be asked to play again.
Social isolation often complicates seizure disorders, and the unpredictability of seizures is a leading factor. Many persons with epilepsy are reluctant to make new friends or to go on dates for fear that a seizure may occur. Impairment of social function contributes to lowered life fulfillment for persons with epilepsy.7
Childrearing is also affected by the unpredictability of seizures. Women may be afraid to carry or be left alone with their infant children for fear that a seizure may occur at an unfortunate moment.
Impact of Neuropsychological Aspects of Epilepsy
Cognitive deficits are associated with several forms of epilepsy. Most prominently, temporal lobe epilepsy is associated with deficits in memory function, which are strongly related to the degree of hippocampal atrophy. Recently, cognitive impairments have been studied in individuals with frontal lobe epilepsy. Deficits in working memory19 as well as in other frontal executive systems tasks have been found. Primary generalized epilepsies are also associated with specific forms of cognitive deficits.20 Even the so-called “benign” Rolandic epilepsy is now recognized as being associated with neurobehavioral abnormalities.3 Memory dysfunction has a strong correlation with lower scores on measures of quality of life.10
Persons with epilepsy have a higher incidence of depression than the general population. Although this relationship is true of all chronic disorders to some extent, depression is more severe among persons with epilepsy than with other conditions. Depression may be directly linked to abnormal metabolic function in the temporal lobes.4,24 The rate of suicide is high in persons with epilepsy, especially when the left temporal lobe is involved.1,5
Psychosis is associated with epilepsy in several settings. Most commonly, the postictal state can be associated with a transient psychosis. The incidence of postictal psychosis is unknown. Risk factors for postictal psychosis include bilateral focus for temporal lobe seizures, clusters of seizures, and long-term presence of the disease.9 Postictal psychosis can last for days and may require hospitalization for treatment. Rarely, patients with longstanding temporal lobe epilepsy may develop interictal psychosis, which is a fixed rather than transient psychotic state. This manifestation can resemble schizophrenia, with paranoia, hallucinations, delusions, and religious ideation common to both. The schizophreniform psychosis of epilepsy is differentiated by preserved interpersonal relationships and affective expression, both of which may be missing in individuals with true schizophrenia.
Social Stigma of Epilepsy
For centuries social stigma and prejudice have been directed against individuals with epilepsy. In the past, epilepsy was sometimes considered a form of possession by the devil or other evil spirits or to have other mystical origins. Irrational laws against persons with epilepsy existed well into this century, including forced sterilization and laws prohibiting marriage. Even today, laws relating to persons with epilepsy are not entirely based on rational examination of evidence. Driving restrictions are applied immediately when a person has a seizure. In contrast, alcoholics are allowed to drive until they have been involved in several accidents or injuries.
Quality of Life and Epilepsy
Until recently, the sole measure of successful treatment of epilepsy was the degree of seizure control. In the past 5 to 10 years, increasing attention has been paid to quality of life as a global measure of the success of treatment and of the impact of the disorder on patient’s lives. Several quantitative rating scales have been developed.23 Factors that most strongly relate to quality of life include complete freedom from seizures (partial control is inadequate) and driving ability (again, usually dependent on complete seizure control). Additional contributors to quality of life include cognitive difficulties, memory complaints, unemployment, school difficulties, depression, and social isolation.
The focus on quality of life as an endpoint is leading physicians to reexamine our approach to the management of epilepsy. For example, most new drugs developed for epilepsy use two measures as clinical trial endpoints: percentage reduction in seizures and the fraction of patients for whom seizures decrease by 50%. None of the current group of new drugs is likely to produce seizure-free outcomes in more than 10% of refractory patients. With the comparatively better success rate of epilepsy surgery at producing seizure-free outcomes, it is increasingly clear that individuals with focal epilepsy should be referred to epilepsy centers early in the course of their illness rather than undergoing long trials of multiple medications.
Costs of Epilepsy
It is very difficult to measure the direct costs of epilepsy, which include the costs of acute care of patients during and after a seizure and the treatment of seizure-related injuries. The costs of routine chronic treatment include outpatient physician visits, diagnostic tests [magnetic resonance (MR) imaging, electroencephalography (EEG)], medications, laboratory monitoring of drug levels, and the routine evaluation of blood counts and blood chemistry. The direct costs incurred at tertiary centers include the costs of EEG-telemetry and epilepsy surgery. The only comprehensive study performed in the United States showed a 5- to 7-year breakeven point for the costs of epilepsy surgery compared to the costs of medical management when only direct costs were considered.12 The direct costs include the costs of rare complications such as Stevens-Johnson syndrome, aplastic anemia, or birth defects caused by medicines.
Just as important but much harder to evaluate are the indirect costs of epilepsy. These are costs of the disease not borne directly by the health care payment system and include costs to the patient such as lost income from missed days at work, unemployment, or underemployment. Family members might bear the costs of transporting a nondriving patient to his or her appointments (including time off from work). Society bears the costs of caring for uninsured patients and of traffic accidents. The indirect costs probably outweigh the direct costs.
Finally, some costs cannot be measured by economics, including altered life paths, missed opportunities, depression, cognitive problems, and the loss of human potential.
Health Care Delivery Relating to Epilepsy
Increasingly, primary care physicians (PCPs) are called upon to provide the first level of care for persons with chronic disorders of all types. However, most PCPs undergo only a brief formal training in neurology. Although epilepsy is present in 0.5% to 1% of the population (a prevalence similar to that of diabetes), PCPs receive minimal formal training in its management. Increasing patient workloads and decreasing time per patient encounter undermine the ability of PCPs to provide counseling on the broad range of issues that confront persons with epilepsy. PCPs can be expected to make an initial diagnosis, begin treatment, and adjust drug doses. They should discuss issues such as compliance, driving, and birth control with their patients and should be alert for signs of depression, cognitive side effects from medications, and drug interactions. The explosion of newly available drugs to treat epilepsy has probably outstripped the ability of most PCPs to stay current, but most are familiar with one or two of the new drugs and should be able to start such medicines appropriately when first-line therapy fails.
Neurologists have more extensive training in and exposure to the problems of managing epilepsy. Neurologists should be able to diagnose epilepsy according to contemporary classification systems and to recognize specific epilepsy syndromes that require special approaches to treatment. Neurologists should be more familiar with the unusual features of seizure medicines than PCPs and should be able to use all of the newly approved seizure medicines. Neurologists should know when to order neuroimaging and electroencephalographic studies. Decisions about whether to treat individuals who have had a single seizure or whether to stop treatment in a person who has been free of seizures for several years are best made by neurologists. However, the community-based neuroimaging available to most general neurologists13 is inadequate to diagnose mesial temporal sclerosis, and patients suspected of having temporal lobe epilepsy should be referred to tertiary centers for their neuroimaging studies. General neurologists are not trained to differentiate seizures from pseudoseizures,11 and patients with uncontrolled seizures or who have suspicious events should be referred for EEG-video telemetry at a tertiary center. Finally, referrals for any patient with suspected focal epilepsy who has not attained complete control of seizures within 2 to 3 years of diagnosis or who have failed trials of two or three different medications should be referred for epilepsy surgery.
Unfortunately, current experience is that most patients with epilepsy do not reach tertiary centers until they have experienced uncontrolled seizures for 10 to 20 years. By this time, these patients may have suffered tremendous social damage. Insurance companies have a peculiar incentive in this regard. They only pay for direct costs, not indirect or noneconomic costs. And, because the average patient does not stay with a single insurer long enough for the long-term benefits of epilepsy surgery to compensate for its immediate costs, many insurers are reluctant to allow patients access to tertiary epilepsy care.
Tertiary epilepsy care is provided at centers staffed by a multidisciplinary team. Epileptologists are neurologists who have completed fellowship training (typically 2 years) in epilepsy management and electroencephalography. A tertiary center would include a neuropsychologist with special interest in epilepsy-related issues, a neurosurgeon with training and experience in the specialized procedures related to epilepsy surgery, and a neuroradiologist knowledgeable in recently available special imaging techniques [e.g., high-resolution MR imaging, positron emission tomography, MR spectroscopy, ictal single photon emission computed tomography (SPECT)].
Services available at a tertiary epilepsy center include EEG-video telemetry for accurate diagnosis of pseudoseizures and for preoperative localization of the seizure focus, special imaging studies as listed above, neuropsychometric studies, access to experimental medication trials, and implantation of vagal nerve stimulators. Epilepsy surgery is a highly effective treatment available only at tertiary centers. Furthermore, most tertiary centers are integrated with community support groups such as the local epilepsy society and rehabilitation programs.
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- Benson DF: The Geschwind syndrome. Adv Neurol 55:411-421, 1991
- Binnie CD, Marston D: Cognitive correlates of interictal discharges. Epilepsia 33:11-17, 1992
- Blum DE, Ehsan T, Dungan D, et al: Bilateral temporal hypometabolism in epilepsy. Epilepsia 39:651-659, 1998
- Carrieri PB, Provitera V, Iacovitti B, et al: Mood disorders in epilepsy. Acta Neurol (Napoli) 15:62-67, 1993
- Chaplin JE, Wester A, Tomson T: Factors associated with the employment problems of people with established epilepsy. Seizure 7:299-303, 1998
- Collings JA: Life fulfillment in an epilepsy sample from the United States. Soc Sci Med 40:1579-1584, 1995
- Derby LE, Tennis P, Jick H: Sudden unexplained death among subjects with refractory epilepsy. Epilepsia 37:931-935, 1996
- Devinsky O, Abramson H, Alper K, et al: Postictal psychosis: A case control series of 20 patients and 150 controls. Epilepsy Res 20:247-253, 1995
- Kendrick C, Trimble M: Repertory grid in the assessment of quality of life in patients with epilepsy: The quality of life assessment schedule, in Trimble MR, Dodson WE (eds): Epilepsy and Quality of Life. New York: Raven, 1994, pp 151-164
- Koblar SA, Black AB, Schapel GJ: Video-audio/EEG monitoring in epilepsy—the Queen Elizabeth Hospital experience. Clin Exp Neurol 29:70-73, 1992
- Langfitt JT: Cost-effectiveness of anterotemporal lobectomy in medically intractable complex partial epilepsy. Epilepsia 38:154-163, 1997
- McBride MC, Bronstein KS, Bennett B, et al: Failure of standard magnetic resonance imaging in patients with refractory temporal lobe epilepsy. Arch Neurol 55:346-348, 1998
- Meadows G: Who will hire truthful epileptics? Postgrad Med 46:128-131, 1969
- Rausch R: Neuropsychological and psychosocial followup of patients with temporal lobectomy surgery for intractable epilepsy: Results at 1-year and 10-years. (Abstract) Epilepsia Suppl 4:S138, 1995
- Reinisch JM, Sanders SA, Mortensen EL, et al: In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA 274:1518-1525, 1995
- Spitz MC: Injuries and death as a consequence of seizures in people with epilepsy. Epilepsia 39:904-907, 1998
- Spitz MC, Towbin JA, Shantz D, et al: Risk factors for burns as a consequence of seizures in persons with epilepsy. Epilepsia 35:764-767, 1994
- Swartz BE, Halgren E, Simpkins F, et al: Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones. Neurology 46:737-747, 1996
- Swartz BE, Simpkins F, Halgren E, et al: Visual working memory in primary generalized epilepsy: An 18FDG-PET study. Neurology 47:1203-1212, 1996
- Trimble MR: Personality disorders and epilepsy. Acta Neurochir Suppl (Wien) 44:98-101, 1988
- Trimble MR: Behaviour changes following temporal lobectomy, with special reference to psychosis. J Neurol Neurosurg Psychiatry 55:89-91, 1992
- Vickrey BG: Advances in the measurement of health-related quality of life in epilepsy. Qual Life Res 4:83-85, 1995
- Victoroff JI, Benson F, Grafton ST, et al: Depression in complex partial seizures. Electroencephalography and cerebral metabolic correlates. Arch Neurol 51:155-163, 1994