Quality of life in epilepsy

ELSEVIER

Review Article

Quality

of Life in Epilepsy

Susan S. Spencer and Peter W. Hunt

In the past several years, there has been substantial growth in health-related quality of life (HRQOL) research in epilepsy. Although physicians have long observed and documented many of the psychosocial problems of patients with epilepsy, the attempt to define and quantify HRQOL in these patients is a new science. As Baker et al. noted, QOL research activity in epilepsy has consistently lagged behind similar research in five other common chronic conditions (1). However, several recent developments in HRQOL research in epilepsy provide the possibility to pursue this area scientifically. The goals of this research are clear. As with treatments for most chronic diseases, treatments for epilepsy often fall short of “curing” disease, leaving patients wtih some suboptimal side effects. For most patients with epilepsy, improving function by decreasing symptoms and illness severity is the main goal of therapy. Clearly, this outcome speaks to more than just a patient’s seizure frequency; it calls for a more complete appraisal of a patient’s overall health, including the psychosocial problems which may bother the patient more than the actual physical severity of the illness. As Fallowfield noted in a recent review: “Illness compromises not only one’s biological integrity, but also one’s psychological, social, and economic well-being” (2). HRQOL assessment seeks to evaluate and integrate these multiple domains into a global appraisal of Received August 21,1995; accepted September 21,1995. From the Department of Neurology, Yale University School of Medicine, New Haven, CT, U.S.A. Address correspondence and reprint requests to Dr. Susan S. Spencer at Department of Neurology, Yale University School of Medicine, Box 208018, New Haven, CT 06520-8018, U.S.A. J. Epilepsy 1996;9:3-13 Q 1996 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

overall well-being. By evaluating overall health beyond seizure frequency alone, HRQOL assessment can help physicians offer care to patients that is more sensitive to their needs. HRQOL can also serve as a more complete measure in epilepsy research. This notion is substantiated by parallel work in hypertension. Croog et al. used HRQOL data to distinguish the effects of captopril from those of propranolol and methyldopa in patients with hypertension (3). Although all three drugs had similar effects on blood pressure, their overall effects on general well-being and HRQOL scales were statistically different in the populations tested. HRQOL outcome research therefore served as a sensitive outcome measure in distinguishing treatments with previously indistinguishable morbidity and efficacy. Similarly, HRQOL data can be used in clinical trials of antiepileptic drugs (AEDs) and in evaluations of epilepsy surgery. Both by enhancing physician understanding of the psychosocial problems experienced by patients with epilepsy and by improving the sensitivity of outcome measures, HRQOL research holds great promise for the field of epilepsy.

HRQOL HRQOL

Definition Instruments

and Requirements

for

Although many different definitions are provided in the literature, HRQOL can be succinctly described as a state of overall health that includes domains of physical, social, psychological, vocational, and economic well-being. Even though some researchers disagree regarding the number of domains that constitute HRQOL, the full range of effects of an illness on an individual can be classified

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S. S. SPENCER AND P. W. HUNT

into at least one of the five domains just described.” Therefore, a comprehensive measure of HRQOL must address all five of these domains in sufficient detail. In addition to addressing the multiple domains of well-being, the ideal HRQOL instrument should evaluate patients according to their own value system and social context; e.g., restrictions on driving because of the diagnosis of epilepsy will probably have a more pronounced effect on the HRQOL of an adult truck driver than it will on an elderly individual who has not driven in years. For this reason, HRQOL instruments should rely heavily on self-reports and should ask patients to relate their functioning to their own goals and expectations. This requirement must also be balanced by feasibility. A self-reported HRQOL inventory that is too long, confusing, or time-consuming will lose its effectiveness. Finally, as with all scientific instruments, HRQOL inventories must pass the strict requirements of validity and reliability. As Johnson noted in a recent review, there are four types of validity that should be met by any scientific instrument: face validity, content validity, construct validity, and criterion validity (4). Face validity requires that a scale contain items that appear to measure what it is intended to measure; i.e., given the definition of HRQOL, does the instrument contain questions that relate to all of the subdomains of HRQOL? Similarly, content validity requires that the instrument or scale adequately sample the domain it is intended to measure; i.e., does the scale have enough questions in each domain to represent overall HRQOL adequately? Conversely, construct validity is a more objective type of validity which requires that the scale exhibit predicted relations with other validated measures. For example, does the scale demonstrate close associations with scales *In addition, there is someconfusion in the literature with regard to terminology. Some investigators have used the term quality of life (QOL) to refer to the overall state of well-being describedherein asHRQOL. They argue that the term HRQOL implies an exclusion of wellbeing domainsthat are affected only indirectly by illness. However, Vickrey and most other researchershave used the term HRQOL to refer to both direct and indirect effects of illness. Indeed, HRQOL is a preferable term because it distinguishes itself from other QOL measures that include well-being domains that are entirely unaffected by illness.However, these are minor issuesof semantics and should not distract from the fact that most researchers,whether they useHRQOL or QOL, are referring to the same multidimensional concept outlined herein. 4 J EPILEPSY,

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that shou!d be related (convergent validity) and negative associations with scalesthat should not be related (divergent validity)? Last, criterion validity requires that a scale discriminate between groups of people defined by criteria external to the scale itself; e.g., does the HRQOL inventory differentiate between patients who are seizure-free and patients who have a high seizure frequency? In addition to these four requirements of validity, the measure must also meet requirements of testretest reliability. Test-retest reliability requires that the scale yield consistent results when applied to the same person or persons under similar conditions at two different times. Ideally, the individual should forget the results of the first test at the time of retest. Because most individuals will change with time, this requirement makes performing testretest reliability difficult. Nevertheless, researchers must approximate these requirements for the HRQOL instrument to be proven reliable.

Early HRQOL Studies Epilepsy Populations

in

Although measuring overall HRQOL with instruments that meet all the above requirements is the ultimate goal, previous studies surveyed common psychosocial problems experienced by epilepsy patients and provided glimpses into separate domains of HRQOL. For example, Harrison and Taylor (5) concentrated on the social, vocational, and economic domains of HRQOL in a 25-year follow-up of ~200 children who were first identified as having had at least one seizure. They reported that only 50% of patients with continuing epilepsy were self-supporting in the community; the remaining 50% were either institutionalized or were invalids at home. The educational and vocational achievement of the patients with continuing epilepsy was also far worse than that of the general population. Consistent with these findings, the patients with continuing epilepsy were also overrepresented in the groups with lower incomes. These results, although drawn from a narrow sample in the vicinity of Oxford, England, highlight some of the general social consequences of childhood epilepsy that persists into adulthood. In a similar study, Britten et al. (6) also investigated the social, vocational, and economic domains of HRQOL. In this longitudinal cohort study, 5,362 individuals born in the United States during March 1946 were contacted every 2 years through adoles-

QOL IN EPILEPSY

cence and every 5 years thereafter. Of this sample, 1.09% were diagnosed with epilepsy at some time during the 36 years. Identifying an epilepsy sample within the general population sample allowed the authors to make several important group comparisons; e.g., the epilepsy cohort members were significantly less likely to be in paid work and were significantly more likely to have been unemployed. The educational and vocational qualifications and marital status of the epilepsy cohort, however, were not significantly different from those of controls (when controlled for social class background). These findings demonstrate that many of the psychosocial problems observed in the more severe epilepsy populations, such as the childhood onset group reported by Harrison and Taylor (5), may not be common in the general epilepsy population. Because the relative severity of this epilepsy population is not fully documented, patients with less severe epilepsy may mask differences that would have been noted in a sample with more severe illness [such as the sample collected by Harrison and Taylor (5)l. In 1988, this issue was readdressed by Thompson and Oxley (7). Instead of investigating the general epilepsy population, they investigated a sample of 92 patients with uncontrolled seizures. In this sample of patients with the most severe epilepsy, 44% received special schooling and only 48% had achieved some form of educational qualification, with the attainment level skewed toward lower level certificates. Like educational achievement, vocational achievement was also low; 47% had experienced periods of unemployment, and 91% of those who were employed had unskilled jobs. Furthermore, when asked to rate their level of satisfaction with their daily occupation as part of the Social Problems Questionnaire (SPQ), 71% rated moderate to severe dissatisfaction. The SPQ was also used to rate satisfaction with social life. It is of interest that the highest percentage of dissatisfaction (73%) was noted in response to questions about social life. Even more remarkable, 68% of the sample admitted having no personal friends and 34% had never formed a true friendship. Concordant with these results, 59% of the patients in this sample were assessed to be highly dependent on their family for their basic needs. Together these results demonstrate that deficits in education, occupation, and social life, although insignificant in the general epilepsy population, are very important in populations with severe, uncontrolled epilepsy. This distinction between the general epilepsy population and the uncontrolled epilepsy popula-

tion was further elucidated by Jacoby, who analyzed a sample of well-controlled epilepsy patients (8). Although 71% of the patients were treated with AEDs, most had been seizure-free for at least 2 years. Of this well-controlled sample, only 12% considered epilepsy a serious illness and only 8% worried about it a lot. Furthermore, only 12% believed that their social activities were restricted because of their epilepsy [in contrast to the findings of Thompson and Oxley (7) in a population with severe epilepsy]. Occupational status in the population in Jacoby’s study (8) was also much better than that in the populations with more severe epilepsy. Indeed, Jacoby reported that 79% of the men and 63% of the women were employed at the time of the interview (comparable to employment in the general population) and that only 3% of those who were unemployed cited epilepsy as the reason (8). Possibly the most important problem in Jacoby’s sample was “felt stigma.” Although the patients did not experience many of the psychosocial problems observed in populations with more severe epilepsy, 32% believed that their epilepsy made it more difficult for them to obtain employment (8). This perceived or felt stigma is distinguished from actual or “enacted” stigma, as defined by Scambler and Hopkins (9), since only 3% reported that they failed to obtain employment because of their epilepsy (8). These results are impressive in that they emphasize the marked differences in aspects of HRQOL that depend on epilepsy severity, the remarkably good HRQOL in well-controlled patients, and the difficulty in generalizing HRQOL observations in any domain. Although the cited studies have investigated the social, vocational, and economic domains of HRQOL, other epilepsy research has concentrated solely on the psychological domain of HRQOL. These studies were discussed recently by Hermann and Whitman (lo), who reviewed studies investigating psychopathology in the general epilepsy population; three of four studies showed a higher incidence of psychopathology in the epilepsy population as compared with the general population. However, when the epilepsy population was compared with populations of patients with nonneurologic chronic illnesses or nonepileptic neurologic illnesses, no differences were noted. Therefore, this higher incidence of psychopathology may be related simply to the chronicity of the disease. Whitman et al., however, demonstrated that of patients who showed some form of psychopathology, psychosis was overrepresented in the epilepsy population as compared with populations of patients with J EPILEPSY,

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other chronic diseases or nonepileptic neurologic disorders (11). Researchers have also investigated whether there is an increased prevalence of psychopathology in temporal lobe epilepsy (TLE) populations as compared with extratemporal epilepsy populations (NTLE). The importance of anterior temporal and limbic structures in the mediation of emotional, sexual, and social behaviors has long led to speculation that TLE may cause a higher incidence of social and psychological dysfunction. Most investigators reported no difference when controlling for seizure severity. Nonetheless, there do appear to be some predictors of psychopathology in epilepsy, including bilateral EEG foci, multiple seizure types, and ictal fear. Hermann and Whitman also reviewed several studies that demonstrated a high incidence of hyposexuality in the epilepsy (particularly TLE) population. As Gastaut and Collumb (12) first reported in 1954, global hyposexuality was observed in most patients with TLE. Hermann and Whitman (10) noted that limbic system dysfunction, general psychiatric status, AED treatment, and social limitations have all been demonstrated to predict hyposexuality in epilepsy patients. However, because of the multifactorial nature of these predictors and their multiple intercorrelations, it is difficult to establish causation. Hermann and Whitman (10) also reviewed studies that reported a high prevalence of interictal affective disorders, including depression and anxiety. Although there were few controlled investigations of these problems in epilepsy, several investigators reported a high incidence of depression and anxiety in both TLE and NTLE. Still other studies have concentrated on cognitive function in patients with epilepsy. These studies were recently reviewed by Trimble (13). Of note is a study by Klove and Matthews in which normal controls were compared with patients with epilepsy and identifiable brain pathology, patients with epilepsy and no brain damage, and patients with brain damage and no epilepsy (14). Klove and Matthews reported that when brain damage effects were controlled for, neuropsychological deficits were still evident in the patients with epilepsy, indicating an epilepsy effect on cognition. Further studies demonstrated that intellectual performance was related to seizure frequency. Most notably, Seidenberg et al., examining test-retest performance on the Weschler Adult Intelligence Scale (WAIS), reported that patients whose seizure frequency was reduced during the intertest period showed significantly more improvements than 6

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those whose seizure frequency was not reduced (15). Still other researchers reported memory impairments, especially in patients with partial seizures arising in the temporal lobes. These studies documenting cognitive impairments as a result of epilepsy are complemented by other studies that document cognitive deficits as a result of AED treatment. Many of these were reviewed by Thompson and Trimble (16). Although the neuropsychological profiles of individual AEDs are still debated, the possible detrimental effects of AEDs on cognitive function are widely accepted.

Development Their Initial

of Specific Applications

Instruments

and

The literature already cited represents a descriptive body of research that identifies problems affecting individual domains of HRQOL (social, economic, vocational, and psychological well-being). The next step in the development of HRQOL research in epilepsy is to integrate many of the problems identified in the studies cited into a measure of overall severity of psychosocial problems in individual epilepsy patients. This challenge was partially met by the Washington Psychosocial Seizure Inventory (WPSI) (17). The WI’S1 consists of 132 yes/no questions subdivided into eight scales:family background, emotional adjustment, interpersonal adjustment, vocational adjustment, financial status, adjustment to seizures, medicine and medical management, and overall psychosocial functioning. It also contains a “Lie” scale that identifies subjects who have a tendency to underreport emotional distress and suffering. Its criterion validity was further established in a study by Wilkus et al. in which the WI’S1 could distinguish people with epileptic seizures from people with nonepileptogenie attacks or pseudoseizures (18). Because the WI’S1 was extensively validated and proven reliable in the tested samples, it has been widely used as an outcome measure sensitive to psychosocial problems specific to epilepsy. Although the WI’S1 may be an effective inventory of psychosocial problems experienced by patients with epilepsy, it cannot be considered a HRQOL instrument. It addresses specific HRQOL domains (social, psychological, vocational, and economic), but it does not have sufficient content validity to measure overall well-being and lacks questions addressing the physical domain of HRQOL entirely. Because the WI’S1 is an inventory of psychosocial

QOL IN EPILEPSY

problems specific to epilepsy, its questions are not broad enough to address the full range of problems covered by true HRQOL domains. Indeed, as Langfitt demonstrated in a recent comparison of the psychometric properties of the WI’S1 and two overall HRQOL instruments, the WI’S1 is relatively insensitive to differences in broad HRQOL scales (19). This insensitivity to differences in broad HRQOL scales makes the WI’S1 useless in comparing patients with epilepsy with patients who have other chronic diseases.Only overall HRQOL instruments are capable of making such comparisons. Because HRQOL instruments measure all five domains of well-being and have broad content validity, they can compare overall well-being across groups of patients with different diseases. This capability of HRQOL instruments spurred the development of new HRQOL instruments for the field of epilepsy. Even though the capability of interdisease comparisons is an important goal, HRQOL measurement in epilepsy must preserve sensitivity to the psychosocial problems specific to epilepsy, the major benefit of the WPSI. This was the major issue confronted by the developers of the first true HRQOL instruments in epilepsy. Clearly, previously validated generic HRQOL instruments already existed, most notably the RAND 36-Item Health Survey (SF-36). The SF-36 and other generic HRQOL inventories had already been used to measure HRQOL in patients with other chronic conditions. However, the scalesof these surveys measure general physical, social, and emotional adjustment and are not sensitive to the specific psychosocial problems observed in epilepsy (e.g., driving, seizure worry). To solve this problem, several groups of HRQOL researchers developed HRQOL inventories that contain both a generic HRQOL core and an epilepsy-specific supplement. One such attempt was made by Collings (20). Although Collings does not purport to measure HRQOL, his scale of overall well-being is conceptually very similar to that of the HRQOL instruments already described. His inventory contains subscales of self-esteem, life fulfillment, social difficulty, physical symptoms, worries, and affect balance. All these subscales were adapted from other previously validated scales. Collings then constructed an overall well-being scale based on the sum of the scores of the individual subscales. When tested in a population of 392 patients in England and Ireland who attend epilepsy support groups (a population with slightly more severe epilepsy than that of the general epilepsy population), the patients with epilepsy scored significantly worse on

all subscales relative to matched non-epilepsy controls. This demonstration of criterion validity, however, fails to demonstrate the sensitivity of the instrument to changes in disease severity. Indeed, because the Collings scale was adapted solely from generic, non-disease-specific scales, its sensitivity to epilepsy populations of differing severities is questionable. Because the Collings scale has not yet been proven to differentiate these groups, its usefulness in epilepsy research remains unknown. Another attempt at developing a HRQOL inventory that is both generalizable to other diseasesand sensitive to problems specific to epilepsy was made by Baker et al. (21). Like the well-being scale developed by Collings (20), the inventory developed by Baker et al. (21) includes several subscales adapted from previously validated instruments; these include a seizure frequency scale, a special seizure severity scale developed by Smith et al. (22), the Nottingham Health Profile (NHP) as a measure of general health, an Activities of Daily Living scale, the Social Problem Questionnaire (SPQ), the Hospital Anxiety and Depression Scale (HAD), the Affect Balance scale, the Profile of Mood States (POMS), and the Rosenberg Self-Esteem scale (RSE). On the average, patients took 45 min to complete this battery of questions. Tested in a population of medically intractable epilepsy patients in the United Kingdom, this scale was used to attempt to differentiate patients treated with the new AED lamotrigine (LTG) from those continuing treatment with established AEDs. Patients electing to continue LTG had significantly better profiles than those who elected not to continue, bolstering the inventory’s criterion validity. Baker et al. (21) also reported construct validity for all of the subscales except the SPQ subscale, which had unacceptable internal consistency and an extremely low variance in the test population. As a result, this subscale was deleted from the revised inventory. However, other potential problems exist with this inventory. No test-retest reliability was demonstrated, and no comparisons with patients with lesser disease severity were made. Without these data, both the reliability and sensitivity to change of this instrument are questionable. Furthermore, the instrument’s feasibility is questioned by its excessive length (an average of 45 min is required for its completion); it may therefore prove an impractical research tool. Smith et al. (22) made an important contribution to HRQOL research with their novel seizureseverity scale, however. Indeed, they demonstrated that the seizure severity scale surpassed seizure fre1 EPILEPSY,

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quency in its ability to predict variance in several psychological factors including self-esteem, locus of control, and anxiety. Seizure severity may therefore be a more appropriate outcome measure than the traditionally used seizure frequency measure because it includes both self-reported and physicianreported measures of disease severity that evaluate the nature of seizures beyond the mere issue of seizure frequency. Other seizure severity scales already exist, including the Veterans Administration (VA) Composite Rating Scale (23) and the Chalfont Scale (24). The VA scale, however, may be too lengthy and difficult to score to be practical as an outcome measure. In addition, the validity and reliability of the Chalfont scale are unknown because the specific techniques used for these processes were not fully explained. The seizure severity scale proposed by Smith et al. (22) may be the best current alternative for measuring seizure frequency in epilepsy patients. Administered with other formal HRQOL inventories, this seizure severity scale can provide important outcome information in both clinical trials of AEDs and epilepsy surgery studies. In itself, however, it cannot measure overall HRQOL. Kendrick and Trimble (25) made yet another attempt at measuring HRQOL in epilepsy patients with their Quality of Life Assessment Schedule (QOLAS). Based on the repertory grid technique, this extensive interview-based tool crafts HRQOL profiles based on the self-reported HRQOL concerns of individual patients. The QOLAS then compares the actual HRQOL status (NOW) to the desired status (LIKE), offering a unique interpretation of overall HRQOL as the difference between these two states. Although this research tool creates a sophisticated, individually crafted measure of overall HRQOL for individual patients, its usefulness as an outcome measure in epilepsy research is limited because of its labor-intensive administration and interpretation. Many of the shortcomings described were overcome by another HRQOL instrument developed by Vickrey et al: the Epilepsy Surgery Inventory-55 (ESI-55) (26). This inventory has a core generic HRQOL scale, the RAND SF-36, which has been extensively validated in other disease populations. In addition, the ESI-55 includes epilepsy-specific questions addressing cognitive function, role limitations due to memory problems, and perceptions of epilepsy. This succinct inventory allows comparisons with other disease populations because it is based on the standard SF-36. In addition, its epi-

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lepsy-specific questions allow sensitivity to the psychosocial problems specific to epilepsy. To test its validity and reliability, the ESI-55 was administered to 224 adult patients who had undergone epilepsy surgery or evaluation for surgery with depth electrode implantation at the University of California at Los Angeles between 1975 and 1990. In this population, internal consistency was adequate in all scales for group comparisons. Furthermore, criterion validity was established by the inventory’s ability to distinguish three classes of seizure outcomes: seizure-free, simple partial seizures, and complex partial and/or generalized tonic-clonic seizures. As a result, the ESI-55 emerged as the first true HRQOL measure to be proven useful in evaluating surgical outcome in epilepsy. The ESI-55 was subsequently expanded by an international team of experts to incorporate a more extensive set of epilepsy-specific psychosocial problems and to be more sensitive to the general epilepsy population (a population with less severe epilepsy than that of the sample chosen for the original validation of the ESI-55). The result of this process was the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) (27). Like the ESI-55, this inventory contains the SF-36 and therefore allows interdisease comparisons. This generic core includes subscales of physical functioning, role limitations due to physical problems, role limitations due to emotional problems, social functioning, bodily pain, emotional well-being, energy/fatigue, and general health. The QOLIE-89 also contains an expansion of this generic core, including a pictorial overall QOL assessment, and a 4%item, epilepsy-targeted supplement. This supplement includes scales of epilepsy-targeted health perceptions, epilepsytargeted social function, working and driving limitations, cognitive function, seizure worry, medication effects, social isolation, and social support. This extensive HRQOL inventory was initially validated (in its original 99-item form) in a multicenter U.S. epilepsy population of 304 adults that included seizure-free patients, patients with mild to moderate seizure frequency, and patients with severe epilepsy. A multitrait scaling analysis of this data then led to the retention of 86 of the original 99 questions and the addition of three additional items (one on satisfaction with sexual function, a visual analogue scale on overall health evaluation, and a question on change in health), distributed into 17 multiitem scales. These data were also used to generate the weightings of the 17 individual scale scores used in determining the overall QOL score. The authors

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also report significant test-retest reliability as well as construct validity (determined by positive patient-proxy correlations and correlations between neuropsychologic tests and self-reported emotional and cognitive function) (27). The QOLIE’s criterion validity was further established by its ability to differentiate populations of patients with different disease severities. Few investigations have yet incorporated the QOLIE-89 in epilepsy research because its development was only recently completed. Nevertheless, it is the most useful HRQOL outcome measure available because of its feasibility, its sensitivity to a wide range of epilepsy-specific psychosocial problems, and its generic HRQOL core facilitating interdisease comparisons.

Further HRQOL

Applications Measurement

of

As already reviewed, several investigations of the common psychosocial problems experienced by epilepsy patients have been made (4-8,12-14). However, most of these studies, with the exception of Jacoby’s study of patients with well-controlled epilepsy (8), have investigated epilepsy in populations with epilepsy more severe than that of the general epilepsy population. Furthermore, no studies have been conducted in the general epilepsy population using validated overall HRQOL measures. Validated HRQOL measures such as the QOLIE-89 can be used to investigate these questions. Because the QOLIE-89 has the generic RAND SF-36 core, the results of such investigations could also be compared with the results of the Medical Outcomes Study (28). Vickrey et al. have already done so in a population of epilepsy surgery patients (29), comparing the RAND SF-36 scale scores of epilepsy surgery patients in three different postoperative seizure outcome groups with those of patients with different chronic illnesses. The seizure-free patients scored better than the patients with hypertension in 6 of 9 domains, better than the diabetic patients in 8, and better than those with heart disease or depressive symptoms in all 9 domains. In contrast, patients continuing to have only simple partial seizures scored better than patients with heart disease and diabetes on the physical health scales, but scored comparably to those patients on the mental and social health scales. In another interesting comparison, the patients still having seizures with impaired consciousness scored worse than the hypertensive, diabetic, and heart disease patients in

emotional well-being and overall HRQOL. These results begin to describe the relative HRQOL of select groups of epilepsy patients. However, comparisons among other groups of epilepsy patients have yet to be made. Comparison studies across countries are also possible. Several such studies have already been completed; e.g., the WI’S1 was used by Dodrill et al. to compare the psychosocial profiles of epilepsy patients of similar severity from four different countries: Canada, Finland, West Germany, and the United States (30). Although the results of their study showed that emotional problems and adjustment to seizures were the most severe problems in each country, the magnitude of the psychosocial problems was different among countries. Notably, the U.S. sample scored worse than those from every other country on each WI’S1 scale, particularly in areas of vocational and financial adjustment. This latter discrepancy may reflect a relative lack of social support for epilepsy patients in the United States. However, the consistently worse psychosocial profiles of the U.S. patients may also be explained by cultural differences in the willingness to report personal problems candidly (reflected by different levels of responses on the “Lie” scale). Alternatively, these discrepancies may reflect the fact that the WI’S1 was originally developed and validated in a U.S. sample of patients. Therefore, the WI’S1 may be most sensitive to the problems specific to the U.S. epilepsy population. This possible cultural bias questions the generalizability of the WPSI to non-U.S. epilepsy populations. A similar study used the Collings overall wellbeing scale to investigate international differences among epilepsy patients with similar disease severity. Comparing epilepsy patients of moderate severity from the United States, United Kingdom, and New Zealand, Collings (20) reported results similar to those of Dodrill et al. (30). The Americans scored significantly lower with respect to well-being on most subscales (although the American sample had slightly more severe epilepsy, as assessedby seizure frequency). Although this study speculates on the possible social reasons for this result, the possibility of cultural bias makes such assertions difficult to prove. However, the studies of Collings (20) and Dodrill et al. (30) lay a foundation for future research into the international differences in HRQOL among epilepsy patients. The QOLIE-89 might be used to investigate these differences, but it will also have to pass tests of cultural bias (since the

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QOLIE-89 was developed exclusively in U.S. populations) before any conclusions can be drawn.

Application of HRQOL AED Research

Measurement

to

As already discussed, AEDs are widely recognized to carry a risk of detrimental effects on cognition and neuropsychological status. Therefore, it is desirable to compare the HRQOL profiles of these different medications in the hope of improving treatment. Smith, Baker, and colleagues have already used the seizure severity scale (31) and the overall HRQOL scale (21) in a trial of the new AED lamotrigine. However, due to extensive cross-over from the LTG group to the control group, no conclusive results were obtained regarding the effects of LTG on seizure severity or overall HRQOL. This problem of cross-over to the control group has made HRQOL evaluations of AEDs using randomized, double-blind trials difficult. Two notable studies have overcome this problem by examining the effect of discontinuing medications from patients who are seizure-free. In the Antiepileptic Drug Withdrawal Study, the Medical Research Council (MRC) AEDWS group investigated the effects of drug withdrawal on psychosocial functioning in a randomized clinical trial of patients (still receiving AED treatment) who had been seizure-free for at least 2 years (32). Follow-up surveys were administered 2 years after randomization. Notably, the analysis showed no increased psychosocial risk in removing patients from medications despite the clinical risk of seizure recurrence, which indicates a psychosocial benefit to AED discontinuation in seizure-free patients. Furthermore, even in patients whose drug discontinuation was unsuccessful (seizures recurred), only 8% regretted the attempt (33). This result further underscores patient awareness of the negative psychosocial impact of AED treatment. Aldenkamp et al. reported a similar result in a study of AED discontinuation in a pediatric population of epilepsy patients (34). They followed 100 children who had been seizure-free for at least 1 year while receiving monotherapy, recording the effects of AED withdrawal using a computerized cognitive test battery. Notably, the 83 patients who continued without medication reported significantly fewer complaints in areas of tiredness and memory problems than they had reported while receiving AED treatment. This result, in agreement with the MRC AEDWS group, reinforces 10

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the possible negative cognitive and psychosocial effects of AED treatment. The opportunity now exists to use the QOLIE-89 as an HRQOL outcome measure in similar wellcontrolled clinical trials of AEDs. Although the psychosocial impact of AED discontinuation in seizure-free patients is well established, the impact on overall HRQOL has yet to be demonstrated. Furthermore, individual comparisons of the HRQOL profiles of new and existing AEDs can also be addressed in this manner. If completed appropriately, these studies could offer important outcome information to prescribing physicians, as Croog et al. have already done in the field of hypertension (3).

HRQOL Surgery

Issues in Epilepsy Research

No conclusive, overall HRQOL outcome investigations of epilepsy surgery have been made. However, there have been several recent studies in the assessment of vocational outcome after epilepsy surgery. Because many of the psychosocial problems in epilepsy (e.g., driving, perceived stigma, social relations) directly affect employment, vocational status is an important domain of overall HRQOL for patients with epilepsy. In one such vocational outcome study, Williams et al. investigated postoperative psychosocial status of 77 epilepsy surgery patients (anterior temporal lobectomy only) by telephone interviews conducted at an average of 3.5 years after surgery (35). From these interviews and information obtained before surgery, the investigators reported that at the time of the postoperative interview, 62% of patients were either employed or enrolled in classes,as compared with only 42% of the same patient sample interviewed during the presurgical neuropsychological evaluation. In addition, 65% of the patient sample were driving postoperatively, as compared with only 25% preoperatively. Although Williams et al. (35) did not specifically indicate the seizure frequencies of each of these postoperative patient populations, the overall number of postoperative seizure-free patients (64%, defined as no seizures in the preceding 6 months or auras only) appeared to correlate well with both these positive outcomes. To investigate further the nature of postsurgical changes in employment (e.g., did the patient get promoted or obtain a better job?), Williams et al. classified patients into “improved,” “stable,” and

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“unimproved” groups; according to this breakdown, 47% were improved, 26% were stable, and 27% were unimproved (35). These results demonstrate favorable vocational outcomes in patients undergoing anterior temporal lobectomies. Vocational outcome was also investigated by Sperling et al. (36), who evaluated employment status changes in 86 patients undergoing temporal lobectomies for refractory epilepsy (3.5-g-year follow-up). Like Williams et al. (35), they documented reductions in both unemployment (25-11%) and underemployment in the postoperative groups. Also in agreement with the results of Williams et al. (35), Sperling et al. (36) noted that these favorable vocational outcomes correlated well with postoperative seizure outcome, with completely seizurefree patients faring best and patients experiencing seizures at least once in every postoperative year faring worst. Although these results indicate favorable vocational outcomes of epilepsy surgery, Sperling et al. (36) also noted that in some instances the vocational improvement did not occur until 6 years after surgery. This is an important finding because, as Sperling et al. explain, a patient’s physical and psychological status may be drastically improved by surgery but it may take time before the patient is socially readjusted and, possibly, even more time for this readjustment to be translated into improved employment status. These recent results in vocational outcomes of epilepsy surgery prompt questions about outcomes of epilepsy surgery in other HRQOL domains. The WI’S1 has been used in several attempts to address these questions. In a retrospective cohort of Norwegian patients operated on between 1949 and 1988, Guldvog et al. (37) noted only very modest psychosocial improvements in the surgically treated group as compared with the medically treated group. However, the validity and the reliability of the scale used are questionable and the study equates epilepsy surgeries from 1949 to 1988, while the procedures have changed in this period. Therefore, this study’s findings, although thought-provoking, are far from conclusive. In response to these questionable findings, other more recent studies have used the WI’S1 as a previously validated and reliable instrument to reevaluate the psychosocial outcomes to epilepsy surgery. In one such study, Chovaz et al. (38) used the WI’S1 to investigate the effects of postoperative seizure control and learned helplessness on psychosocial function in a 5-year follow-up study. Of the population tested, 74% reported improvement in seizure control, 85% reported lifestyle improve-

ments, 65% reported a positive personality change, and 47% reported improved mood. This study also showed a significant relation between seizure relief and overall psychosocial adjustment as measured by the WPSI. Patients who had >90% reduction in seizure frequency had statistically better psychosocial adjustment than those with less seizure reduction. Chovaz et al. (38) also noted that high scores on a learned helplessnessscale correlated with poor psychosocial adjustment. Unfortunately, because no psychosocial data were collected preoperatively, the critically important information on change in status is unavailable. Seidman-Ripley et al. also used the WI’S1 in an outcome study for epilepsy surgery (39). Unlike Chovaz et al. (38), they administered the WI’S1 both before and after surgery (l-year follow-up). In this study, they demonstrated reductions in all psychosocial problem scales (except for family background) for postoperatively seizure-free patients (15 of 30 patients undergoing epilepsy surgery). Although this is an important finding that challenges the inconclusive results of Guldvog et al. (37), only 15 patients were included in this seizure-free sample. Therefore, further investigations are necessary before any conclusions can be drawn. Other recent work with the ESI-55 has also helped lay the foundation for future HRQOL outcome studies in epilepsy surgery: Vickrey et al. recently evaluated 11 different seizure frequency classification schemesfor their sensitivity to changes in ESI-55 scores (40). In their study, 133 patients undergoing epilepsy surgery were evaluated postoperatively using 11 different seizure frequency classification schemesand the ESI-55 as a HRQOL measure. Notably, there was significant variation in the ability of each seizure classification scheme to reflect changes in HRQOL profiles. In particular, no HRQOL differences were noted between seizurefree patients who were and who were not receiving AED treatment. Furthermore, mean overall ESI-55 scores for seizure-free patients were nine points higher than those of patients who had only auras. This distinction between seizure-free patients and patients experiencing auras challenges many of the seizure frequency classification schemes that fail to distinguish these two outcomes. Vickrey et al. (40) have therefore proposed a new seizure frequency classification scheme that is sensitive to HRQOL changes as measured by the ESI-55. This revised seizure frequency classification scheme can now be used to accompany HRQOL outcome studies in epilepsy surgery. None of the studies already described has used a validated HRQOL instrument to / EPILEPSY,

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investigate outcomes of epilepsy surgery in a longitudinal design. Because change in HRQOL is the outcome of interest, only longitudinal studies using validated HRQOL instruments can be conclusive. With the tools now available to perform such studies, the opportunity exists to answer the longdebated questions of the efficacy of epilepsy surgery in improving HRQOL.

HRQOL in Pediatric with Epilepsy

Patients

A related group of studies has investigated HRQOL in children with epilepsy. Because adults and children do not share the same concerns, value systems, and social contexts, separate instruments are needed to evaluate pediatric populations. Indeed, although the domains of HRQOL in adults are physical, psychological, social, vocational, and economic well-being, the domains of HRQOL in children must be defined separately. Another difference in HRQOL assessment for children arises when the issue of self-report is considered. Unfortunately, because self-report HRQOL questionnaires can often be unreliable in children, parental surveys are often used. Given the problems inherent in evaluating an individual’s HRQOL through a proxy, these studies have not been as conclusive as the corresponding adult studies. In one study, Hoare investigated HRQOL in children with moderate to severe epilepsy using two parental self-completed questionnaires; the modified impact of Epilepsy Schedule and the Holroy Questionnaire on Resources and Stress (41). The results demonstrated that epilepsy had the greatest impact on children with intractable epilepsy and additional disabilities, bolstering the criterion validity of the scales used. Furthermore, this study helped define the domains of HRQOL in children. The group of children with the most severe epilepsy showed significant problems in areas of epilepsy management and medication effects, child adjustment and development, and family life. These areas are therefore proposed to be central domains of HRQOL in children. Another study of the HRQOL of children with epilepsy was conducted by Austin et al. (42). Basing their list of HRQOL domains in children on HRQOL domains established in adults, they proposed using physical, social, psychological, and school-related (substituting for occupational) wellbeing as the relevant domains for childhood 12

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HRQOL (42). To measure health in these different domains, they interviewed the children’s mothers and administered a variety of both self-report and proxy report (school teacher reports as well) inventories. The performance of the children with epilepsy in each of these domains was then compared with that of children with asthma. The major finding was that children with moderate epilepsy had a relatively more compromised HRQOL in the psychological, social, and school-related domains than did asthma patients, even though the children with epilepsy were having fewer illness episodes. This finding draws attention to the special needs of children with epilepsy. The instruments used in evaluating HRQOL in children are in their infancy, and the present results can be only a foundation for future research.

Conclusions Outcome research in adults with epilepsy has finally progressed to awareness and early implementation of measures of overall HRQOL in specified groups of epilepsy patients using validated instruments such as the QOLIE-89. This HRQOL information will help broaden physician awareness of the psychosocial problems experienced by epilepsy patients, leading to more compassionate and comprehensive care. Furthermore, these HRQOL data can serve as an additional outcome measure in clinical trials of new AEDs and in epilepsy surgery. These new avenues for research offer limitless potential for the improvement of treatment of epilepsy and in the understanding of its impact on adults. The amount of data available on HRQOL in children with epilepsy, however, lags far behind that available in adults. Indeed, HRQOL in children must be more clearly defined by identifying areas of concern, using self-reports, proxy reports, and the opinions of experts. Furthermore, validated and reliable instruments need to be adapted for use in pediatric populations before clinically useful information can be gathered. Likewise, the potential for improved treatment and understanding in all domains of HRQOL is enormous.

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