The Neuropsychological Evaluation of High-Functioning Patients with Epilepsy




© Springer Science+Business Media New York 2015
William B. Barr and Chris Morrison (eds.)Handbook on the Neuropsychology of EpilepsyClinical Handbooks in Neuropsychology10.1007/978-0-387-92826-5_14


14. The Neuropsychological Evaluation of High-Functioning Patients with Epilepsy



Sarah G. Schaffer 


(1)
Comprehensive Epilepsy Care Center, Cushing Neuroscience Institute, Hofstra North Shore-LIJ School of Medicine, 611 Northern Blvd, Suite 150, Great Neck, NY 11021, USA

 



 

Sarah G. Schaffer



Keywords
EpilepsyNeuropsychologyNeuropsychological assessmentAdultsTest batteryEpilepsy surgeryAntiepileptic drugsQuality of lifeEmployment


Epilepsy is a heterogeneous disorder with countless possible presentations. Knowing that someone has a diagnosis of epilepsy tells you very little about that person’s experience. There are numerous factors that might moderate the impact of this diagnosis on any one person’s life. Issues directly related to the occurrence of seizures might include type/severity of seizures, frequency with which they occur, predictability of occurrence (e.g., only at night, certain time of the month), presence or absence of warning signs or “aura,” level of postictal debilitation, and frequency of injury (e.g., tongue biting, falls, etc.). However, there are also secondary factors to be considered that are unique to each individual. For example, not being able to drive might be more of a burden on a mother with young children living in a rural community than it would on a businesswoman living in a major metropolitan area with a well-connected public transportation system. Conversely, while that same businesswoman might not be impacted by her inability to drive, the cognitive impact of seizures and the cognitive side effects of medications might make it difficult for her to complete her work-related activities.

Along these lines, in many professions the competition for advancement can be fierce (e.g., law, finance, academia). While any “edge” can bump a person up a rung on the ladder toward success, the inverse is also true. The legality of denying someone a job or a promotion because of factors related to medical status is not in dispute. But whether this is “legal” or not is irrelevant, as this is reality. While the stigma associated with epilepsy might result in discrimination based on faulty perceptions by employers and co-workers, the direct consequences of uncontrolled seizures, such as lost days of work and mental clouding associated with antiepileptic medications, might be just as counterproductive to employment goals. Furthermore, most people with refractory epilepsy are on high doses of antiepileptic medications and/or polytherapy (i.e., prescribed multiple medications), which increases the likelihood of such adverse medication side effects.

In light of these issues, it becomes clear that the aim of neuropsychological evaluations of patients with epilepsy is multifactorial. Presurgical evaluations do not simply boil down to lateralization of seizure focus and prediction of postsurgical cognitive decline. Rather, a holistic approach that accounts for the full spectrum of cognitive and psychosocial issues unique to each patient is required. As comprehensive neuropsychological evaluations involve examination of both cognitive and “psychological” factors that impact upon a person’s overall level of functioning, the neuropsychologist might be more likely to consider the entire range of issues that are coming into play and as such might be in the best position to advocate on the patient’s behalf. To this end, it is also helpful to know some of the issues that are common among specific subsets of patients. This chapter aims to delineate such potential issues as they pertain to high-functioning patients, that is, those who have demonstrated an ability to maintain active professional careers.


Consequences of Epilepsy


It is well established in the literature that seizures can have an adverse impact on brain functions. The extent to which patients actually experience declines in cognition due to seizure activity depends on a number of factors, including seizure type (focal vs. generalized), seizure frequency, age of onset, and number of years with seizures. There are several “secondary” factors (i.e., those not directly related to seizures) that can also impact cognition, including the presence of underlying psychopathology (which is seen at higher rates in epilepsy patients than in the general population), the presence of a lesion, and medication side effects. There is considerable evidence to suggest that these factors work in concert with each other to produce the subjective experience of cognitive decline that is so often reported in this patient population.

The most common cognitive complaint in patients with epilepsy is that of memory difficulties. Such complaints are of course validated by decades of research showing the selective impact of seizures on memory functioning. Other common complaints include mental slowing and problems with attention. While the impact of epilepsy on neuropsychological functioning is well established in the research literature, it should be noted that a number of studies have found that subjective complaints do not always correlate with objective impairments. The first part of this chapter provides a brief review of the literature related to cognitive and psychosocial functioning in patients with epilepsy, as well as a brief introduction of the various factors that are associated with magnification of subjective cognitive impairment in this population. The goal of such a review will be to delineate for the clinician the potential pitfalls to be aware of when attempting to identify the salient issues to address when rendering conclusions. The second part of this chapter focuses on specific issues related to the comprehensive neuropsychological evaluation of high-functioning epilepsy patients.


Cognitive Impact


Numerous studies have shown that cognitive impairments in people with chronic epilepsy extend beyond memory difficulties to include problems related to attention and concentration, slower information processing and psychomotor speed, language deficits, and executive dysfunction when compared to performances of normal controls on objective neuropsychological tests.

The poorest cognition is associated with early age at seizure onset and, similarly, longer duration of epilepsy, especially in the presence of a history of generalized tonic–clonic seizures, repeated episodes of status epilepticus, and increased exposure to antiepileptic drugs (AEDs). The age of seizure onset represents a particularly important variable related to degree of cognitive impairment. Childhood-onset temporal lobe epilepsy has been associated with a generalized adverse neurodevelopmental impact on brain structure and function (Hermann et al. 2002; Hermann, Seidenberg, & Bell, 2002). Late-onset patients exhibit considerably fewer volumetric and cognitive abnormalities compared with healthy controls despite a history of chronic temporal lobe epilepsy (16.2 years). Hermann and colleagues (2007) performed a cluster analysis using comprehensive neuropsychological data from 96 patients with chronic temporal lobe epilepsy and 85 healthy controls, and three distinct cognitive subgroups or phenotypes were identified: (1) minimally impaired (47 %), (2) memory impaired (24 %), and (3) memory, executive, and speed impaired (29 %). Common characteristics of patients in the most cognitively impaired group (Cluster 3) included older age at evaluation, longest duration of epilepsy, higher number of antiepileptic medications, and more abnormal brain volumes (total, white matter and CSF). They also showed the most adverse cognitive course, especially when compared to Cluster 1. Although not significant, there were meaningful trends related to other clinical seizure variables in the Cluster 3 group, including greater number of lifetime GTCs, history of status epilepticus, and presence of initial precipitating injuries. Consistent with results from their earlier study regarding the differential impact of earlier age of onset on cognitive prognosis, Cluster 3 was characterized by earlier neurodevelopmental insult. It should be noted that although Cluster 1 exhibited the most intact cognition of the three groups, their performance on measures of language, immediate and delayed memory, executive function, and psychomotor speed was nevertheless significantly worse than that of controls.

The inverse relationship between age of onset and degree of cognitive decline can likely be attributed to that fact that there is greater opportunity for acquisition of skills in childhood prior to seizure onset in those patients who develop seizures later. It is, thus, noteworthy that later age of onset has also been associated with increased risk of postsurgical decline. This might reflect the fact that although these patients may have avoided the neurodevelopmental “hit” seen in patients with younger onset, thereby resulting in a higher level of functioning at the time of surgical intervention, this increases the likelihood that the epileptogenic zone involves functional tissue. Studies have indicated that cognitive decline is determined more by the amount of functional tissue resected than the ability for remaining tissue to support cognitive functions (Chelune, 1995).


Cognitive Prognosis Associated with Chronic TLE


When counseling patients who are in the process of deciding whether or not to undergo surgical intervention of intractable seizures, there are many issues that must be considered. However, with high-functioning patients, none is more relevant than the potential impact on cognition. Therefore, it is necessary to be able to communicate not only the risks and benefits of going forward with surgery but also the risks associated with ongoing seizure activity should they choose not to move forward. In order to do this, one must be familiar with the literature regarding the cognitive prognosis associated with chronic epilepsy.

There are some in the field who propose a neurodegenerative model when characterizing the progression of cognitive decline associated with ongoing seizures. In a large cross-sectional study specifically intended to examine this issue, Helmstaedter and Elger (2009) compared the memory profiles of patients with chronic intractable temporal lobe epilepsy at varying stages of life to those of healthy controls. They found an initial discrepancy in the acquisition of learning and memory skills during childhood and particularly during adolescence that resulted in an earlier “learning peak” in the epilepsy patients (16–17 years vs. 23–24 years). Subsequent declines in performance related to normal aging ran in parallel (i.e., there was not a steeper decline in the epilepsy group), but because of the initial distance in memory abilities between the groups, those with epilepsy reached very poor performance levels much earlier than controls. It was concluded that although there does not appear to be a progressive and/or accelerated decline related to chronic seizures in patients with TLE, the negative interaction of the initially established damage with the normal aging process results in reduced reserve capacities at an older age (Helmstaedter & Elger, 2009). These results support the notion that poor cognitive functioning is related to neurodevelopmental processes in those patients with earlier age of onset. Furthermore, they suggest that rather than benefiting from the increased plasticity that is commonly ascribed to the developing brain, the presence of recurrent seizures during development appears to be associated with an adverse effect on both brain structure and function.

In his review of the literature on cognitive progression in epilepsy, Seidenberg noted that duration of epilepsy appears to be the most reliable predictor of cognitive decline. However, he further pointed out that duration of epilepsy likely signifies the presence of a more complex and/or severe epilepsy syndrome. At the very least, the duration of epilepsy increases the possibility of exposure to factors that result in neuronal damage (Seidenberg, Pulsipher, & Hermann, 2007). Hermann and colleagues looked at the cognitive trajectories of patients with chronic TLE and found that most patients (70–75 %) appeared to have an unproblematic prospective cognitive course. Skills that were more vulnerable to decline (i.e., decline seen in >25 % of patients) included confrontation naming, delayed visual memory, delayed verbal memory, and bilateral motor speed (Hermann, Seidenberg, Dow, & et al., 2006). In general, the patients with adverse cognitive outcomes were older, with longer duration of epilepsy, lower baseline full-scale IQ, and quantitative MRI abnormalities at baseline. Baseline volumetric abnormalities and lower IQ were the strongest predictors of abnormal trajectories in IQ, language, perception, memory, executive skills, and motor coordination over a 4-year period.

The findings that patients who exhibited significant adverse cognitive outcomes were characterized by significantly lower baseline full-scale IQ are consistent with the general notion of increased cognitive vulnerability among those with lower intellectual capacity. In a study that examined long-term outcomes in individuals who had childhood-onset epilepsy now aged 20 years and older, Wakamoto and colleagues concluded that patients who had normal intelligence had more favorable prognosis (Wakamoto, Nagao, Hayashi, & Morimoto, 2000). It stands to reason that high-functioning patients have avoided the neurodevelopmental hit that appears to characterize those patients with poorer baseline functioning, thereby allowing them to acquire the skills needed for a stronger cognitive foundation. Interestingly, and perhaps more germane to the goals of this chapter, this pattern is opposite of that observed following anterior temporal lobectomy for the treatment of intractable seizures. That is, those with the least amount of cognitive impairment going into surgery experience the greatest postsurgical declines (at least with respect to verbal memory), whereas the inverse is true of individuals with significant presurgical cognitive deficits. Stated another way, those with normal neurocognitive profiles going into surgery have more to lose. Helmstaedter pointed out in his discussion of the neuropsychological aspects of epilepsy surgery (2004) that although patients with better baseline memory show greater losses than patients with poor baseline performance, those who are better preoperatively will nevertheless be better postoperatively. That being said, for some patients the prospect of even mild memory decline might be unacceptable. Indeed, this issue might be of particular concern for the population under consideration in the current chapter, as a general assumption would be that their status as “professional/high-functioning” individuals almost by definition implies a certain degree of intact cognition (or rather precludes the presence of significant and/or widespread impairments). However, it is possible that the relative stability of cognitive functions seen in these patients can be attributed to the development and/or use of compensatory strategies that are made possible because of higher cognitive reserve seen in these patients.


Cognitive Effects of Antiepileptic Medications


Problems with learning and cognition have frequently been cited among the primary disadvantages of having epilepsy (Hayden, Penna, & Buchanan, 1992), and the majority of patients with epilepsy attribute their impairments to the side effects of their antiepileptic medication (Carpay, Aldenkamp, & van Donselaar, 2005). There are some general patterns to follow when considering the potential impact of medication side effects on cognition. Newer agents tend to produce fewer side effects than older drugs (e.g., carbamazepine and phenobarbital), with the exception of topiramate (Topamax), which is a newer medication that has consistently been shown to have an adverse impact on cognition. Patients on topiramate are more likely to discontinue this medication due to cognitive side effects. Regardless of the type of medication used, there is a dose-related effect on cognition (even at therapeutic blood serum levels), with polytherapy resulting in more adverse effects than monotherapy.

Unfortunately, given that surgery is considered for patients who are refractory to medications, these patients are more likely to be prescribed high doses and/or multiple medications, and in fact for many the desire to reduce the number of medications is a primary motivation in seeking surgery. Uijl and colleagues found that among 173 patients who were well controlled on medication, 67 % nevertheless reported moderate to severe subjective complaints. Cognitive complaints were reported most frequently, and the prevalence and severity of complaints were associated with AED polytherapy and higher scores on “psycho neuroticism” on the Dutch version of the Symptom Check List (SCL-90) (Uijl et al., 2006). The relationship of self-reported complaints and high levels of neuroticism has been reported in other studies as well (Vermeulen, Aldenkamp, & Alpherts, 1993).


Subjective Cognitive Complaints


While the potential impact of chronic epilepsy on neuropsychological status is not in dispute, patients’ complaints of cognitive impairment (i.e., their subjective experience regarding the severity and functional impact of such impairments) are not always borne out via objective neuropsychological evaluation. Numerous studies have shown that self-reported cognitive complaints do not generally correlate with actual impairments. In general, research has supported an inverse relationship between subjective and objective impairment. That is, more severe cognitive complaints are associated with milder impairment on objective testing, and vise versa. One study that examined the hypothesis that more complaints might be seen in patients with higher cognitive demands in daily life found the inverse to be true (although the effect was mild; Gleissner, Helmstaedter, Quiske, & Elger, 1998). Several studies have indicated a much stronger relationship between subjective complaints and mood than is seen between either subjective and objective cognition or mood and objective cognitive performance (Hayden et al., 1992; Liik, Vahterb, Gross-Pajub, & Haldrea, 2009; Marino, Meador, Loring, Okun, Fernandez, Fessler, et al., 2009; Piazzini, Canevini, Maggiori, & Canger, 2001).

Given these findings, it is important to try to tease out the relative contributions of each factor to the overall profile, using validated neuropsychological and psychological measures, and to counsel the patient when discrepancies between objective impairment and subjective experience arise.


Psychosocial Impact


The psychosocial impact of epilepsy can be profound. Results from multiple population-based surveillance studies representing nearly half of the United States indicated that compared with healthy controls, adults with a history of active epilepsy consistently reported higher rates of unemployment, lower income (<$25 K), lower education, and being single compared with people without epilepsy. Furthermore, those patients with the most active epilepsy (i.e., seizures within the past 3 months) were most likely to report more mentally and physically unhealthy days and more limitations on activity (Kobau et al., 2004, 2007, 2008; Kobau, Gilliam, & Thurman, 2006; Tellez-Zenteno, Patten, Jette, Williams, & Wiebe, 2007).

In a large population-based study conducted in the United Kingdom, psychiatric disorders were found to occur twice as often in patients with epilepsy as in the general population (Gaitatzis, Carroll, Majeed, & W Sander, 2004). Depression is the most frequently diagnosed psychiatric disorder among people with epilepsy. The factors that have been associated with the increased risk of depression in this patient population include employment status, social support, stigma, self-management, financial strain, and activity restriction due to seizures (Reisinger & DiIorio, 2009). In a survey of 503 patients with intractable epilepsy, almost half (46 %) of those surveyed agreed that epilepsy often caused them to suffer from depression (Wheless, 2006). Patients with intractable temporal lobe epilepsy with the additional syndrome of mesial temporal sclerosis have been found to be at an even higher risk of developing psychiatric disorders, with lifetime prevalence rates up to 80 % (Gaitatzis, Trimble, & Sander, 2004; LaFrance, Kanner, & Hermann, 2008)! Not only is the lifetime prevalence of major depression in epilepsy patients far greater than that estimated for the general population (5–25 % according the DSM-IV-TR), but it is almost double the estimated prevalence rate of 20–25 % that is cited in the DSM-IV-TR as occurring in other chronic or severe general medical conditions (e.g., diabetes, myocardial infarction, carcinomas, stroke). These statistics are all the more concerning given consistent evidence implicating depression as one of the strongest predictors of reduced quality of life in patients with refractory epilepsy (Perrine et al., 1995). Despite the focus on depression in epilepsy over the past decade, studies indicate that it is woefully underdiagnosed and largely untreated (Boylan et al., 2004).


Quality of Life


While depression has been identified as an overarching factor related to poor outcome in patients with epilepsy, quality-of-life research has uncovered a variety of specific factors that are associated with patients’ overall sense of well-being. Perceived stigma has emerged as one of the primary issues leading to reduced quality of life in epilepsy patients. Goffman conceptualized stigma as “a loss of status and power resulting from the separation of those stigmatized from the general population based on a characteristic that has been culturally defined as different and undesirable” (Goffman, 1963). In epilepsy patients, stigma is associated with low self-esteem, self-efficacy, and sense of mastery, perceived helplessness, increased rates of anxiety and depression, increased somatic symptomology, and reduced life satisfaction (Jacoby, Snape, & Baker, 2009). In a study out of the Netherlands, stigma accounted for twice the amount of variance in QOL scores as did clinical variables such as seizure frequency and antiepileptic drug side effects, and it was identified as the fourth most important factor in determining QOL after psychological distress, loneliness, and adjustment (Suurmeijer, Reuvekamp, & Aldenkamp, 2001). Results of a recent study showed that reported levels of stigma were associated with interactions of seizure worry and employment status, self-efficacy and social support, and quality care and age at seizure onset (Smith et al., 2009). Regarding employment status, the highest level of stigma was reported by individuals who were disabled or unemployed and reported a higher level of seizure worry, followed by those who were disabled or unemployed but reported a lower level of seizure worry; the lowest level of stigma was reported by those who were employed or “other” (not working but student, housewife, retired, etc.) and reported lower level of seizure worry. It should be noted that people with epilepsy do not universally feel stigmatized by their disorder. In an older surveillance study conducted by Ryan, Kempner, and Emlen (1980), 81 % of the 445 respondents felt that they had been treated fairly in society, and 70 % felt neither unreasonably limited nor treated differently because of their epilepsy (Ryan et al., 1980).

Researchers have also been concerned with identifying those factors that might be associated with better psychosocial adjustment in patients with epilepsy. Resilience, for example, has been found to be associated with better QOL. Sociodemographic characteristics such as gender, education, and income level have been found to be highly predictive of resilience, with poorer resilience manifested by women and individuals who had lower levels of education and lower income (Campbell-Sills, Forde, & Stein, 2009). There is a positive association between resilience and cognitive reserve (as indicated by higher educational level or occupational attainment and increased participation in mindful activities). The well-established relationship between generalized cognitive impairment and duration of epilepsy has been shown to be attenuated (to nonsignificant levels) by having more years of formal education (Oyegbile et al., 2004). The authors suggest that years of education may, in fact, be a marker “for those who, at the outset of the disorder, are on different trajectories regarding educational attainment and lifespan cognition.” In fact, the role of educational level as a predictor of QOL in adults has been emphasized in a number of studies (Loring, Meador, & Lee, 2004; Pulsipher, Seidenberg, Jones, & Hermann, 2006). Socioeconomic status has also been identified as an important predictor of QOL in patients with epilepsy (Alanis-Guevara et al., 2005), and Senol and colleagues found that while income and education predict overall QOL, only income was found to significantly predict mental and physical health and cognitive function scores in a multiple regression analysis (Senol, Soyuer, Arman, & Ozturk, 2007). Therefore, in high-functioning adults, the potential for loss of income has far-reaching implications.


Impact on Employment


In a review of the literature regarding employment and epilepsy, Smeets et al. (2007) noted that employment is seen by many as an important ingredient of the quality of life of people with epilepsy. Employment is considered to be a significant predictor of well-being of people with epilepsy and a very important factor in psychosocial adjustment. In a large population-based study by Jacoby (1995), employed people with epilepsy experienced fewer psychosocial problems than unemployed people with epilepsy (Jacoby, 1995). There is little agreement in the literature on specific unemployment and underemployment rates, which vary widely between communities and countries. It is generally accepted, however, that people with epilepsy are more likely to be employed in unskilled and manual jobs. Some studies suggest a relationship between seizure type and employment status, with increased likelihood of being unemployed for patients classified as having GTC seizures (Jacoby, Baker, Steen, Potts, & Chadwick, 1996) and decreased likelihood of attributing current employment situation to epilepsy in patients who were in remission with respect to seizure activity (Chaplin, Wester, & Tomson, 1998). Although seizure frequency is an important factor determining employment status, it may not be the most important factor to consider. Other factors that can play an important role in predicting employment status include medication side effects, stigma, and psychosocial variables such as low self-esteem, passive coping style, and low self-efficacy. The impact of employment status on self-esteem and self-image has been established. Some argue that the stigma associated with having a diagnosis of epilepsy is one of the most critical barriers to employment. Stigma is associated not only with discriminatory practices, but patients often internalize the negative attitudes of others and come to view their epilepsy in a similar light. Because of this potential for discrimination, people with epilepsy are often hesitant to disclose their epilepsy status to employers. Problems at work can lead to a lack of opportunities for career advancement, and studies suggest that many people with epilepsy do not reach the employment potential corresponding to their qualifications and age.

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Sep 24, 2016 | Posted by in NEUROLOGY | Comments Off on The Neuropsychological Evaluation of High-Functioning Patients with Epilepsy

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