Psychiatric Aspects of Epilepsy Surgery

Antoaneta J. Balabanov

Andres M. Kanner

Introduction

Epilepsy surgery has become an established treatment for patients with medically intractable partial epilepsy (1). Indeed, the likelihood of seizure freedom on any additional antiepileptic drug (AED) trial is less than 5% when patients with partial epilepsy continue to experience seizures despite two to three optimal monotherapy trials with AEDs (2). On the other hand, anterotemporal lobectomy (ATL) for the treatment of mesial temporal sclerosis (MTS) can yield a seizure-free state of 50% to 70%, although lesionectomy in the temporal lobe has been associated with a 50% to 60% seizure-free rate (3). Patients with idiopathic temporal lobe epilepsy (TLE) and extratemporal epilepsy may have a lower probability of seizure freedom (30% to 50%), but even this is significantly better than the probability of becoming seizure-free with AEDs. In addition, the recent advances in neuroimaging technology have facilitated the localization of the epileptogenic area in patients with nonlesional temporal and extratemporal epilepsies, thereby increasing the success of postsurgical seizure outcome.

To be considered for surgery, patients must have a well-localized epileptogenic area that is amenable to surgical resection and/or multiple subpial transection (MST) with no or minimal risks. ATLs are by far the most common surgical procedures performed today in adults in most epilepsy surgical programs, although extratemporal lobectomies (ETLs) are more frequent in pediatric patients. Among the latter, frontal lobectomies are performed most frequently (1,2). Other types of surgical procedures include hemispherectomy, which is considered in patients with widespread hemispheric damage, inflammatory processes such as Rasmussen’s encephalitis, and/or diffusely distributed cortical malformations in one hemisphere (3). Finally, corpus callosotomy has been used for patients with secondary generalized epilepsy, particularly those with drop attacks resulting from tonic and atonic seizures (4), although it has been used less frequently since the advent of the vagal nerve stimulation treatment. It has also been used in patients with partial epilepsy (very often frontal lobe epilepsy) with secondary generalization in whom the seizure onset cannot be identified (5).

Patients with medically intractable epilepsy are a group at high risk of suffering from mood, anxiety, psychotic, and attention deficit disorders. The prevalence rates of these disorders are several fold higher than those of the general population (6, 7, 8, 9, 10) (Table 24.1) and than those of patients with well-controlled seizures. Therefore, patients being considered for epilepsy surgery are likely to suffer from one or more types of comorbid psychiatric disorders.

Yet, despite the relatively high psychiatric comorbidity, psychiatric evaluations are “usually” not included in the presurgical evaluations of every patient being considered for surgery. Indeed, these are often addressed only after the onset of disabling psychiatric symptoms. This problem is compounded by the fact that the clinical presentation of psychiatric comorbidities can often differ between patients with and without epilepsy and hence go frequently unrecognized by the treating physician. In many cases, the patient would have suffered from the psychiatric disorder for a long time and assumes that the existence of these psychiatric symptoms is “normal” in the setting of a seizure disorder. In addition, some patients (and family members) refuse to report their psychiatric symptoms with the epileptologist for fear of lowering their “chances” for surgery. Not surprisingly, patients and their physician are often caught unprepared upon the occurrence of postsurgical psychiatric problems.

TABLE 24.1 Prevalence Rates of Psychiatric Disorders in Patients with Refractory Epilepsy and the General Population

Psychiatric Disorder	Prevalence Rates
Psychiatric Disorder	Epilepsy	General Population
Depression	30%–50%	3.3%: dysthymia 5%–17%: major depression
Anxiety disorders
Generalized anxiety	15%–25%	5%–7%
Panic disorder	5%–21%	0.5%–3%
ADHD	12%–37%	4%–12%
Psychosis	2%–9%	1%
ADHD, attention-deficit hyperactivity disorder.

Comorbid psychiatric disorders have a significant impact on epilepsy surgery at several levels. These include the following:

Presurgical psychiatric comorbidities as a potential risk for postsurgical psychiatric complications
The type of postsurgical psychiatric complications: (i) de novo, (ii) exacerbation or recurrence of presurgical disorder
Postsurgical remission or improvement of presurgical psychiatric comorbidities
The impact of presurgical psychiatric pathology on postsurgical seizure outcome
The impact of postsurgical seizure outcome on postsurgical complications and long-term psychiatric comorbidity
The impact of presurgical and postsurgical psychiatric disorders on the ability of the patient to adjust to a seizure-free life, including the potential to obtain gainful employment
The adequacy of patients with comorbid psychiatric disorders to become candidates for epilepsy surgery

These seven points will be reviewed in some detail in this chapter.

Psychiatric Evaluation as Part of the Presurgical Workup

It follows from the discussion in the preceding text that every single patient being considered for epilepsy surgery should be expected to undergo a presurgical psychiatric evaluation. Unfortunately, that is not the case in most centers, as shown in a recent survey carried out among the 88 epilepsy centers belonging to the National Association of Epilepsy Centers (Kanner AM, submitted). The survey consisted of seven questions that enquired about the availability and use of psychiatric and neuropsychological evaluations during presurgical workups of candidates for epilepsy surgery. It also investigated the concerns of these centers for the development of postsurgical psychiatric complications. Of these 88 centers, only 47 (53.5%) responded to the survey. Only 20% of the 47 centers performed a psychiatric evaluation in every patient being evaluated for ATL. In 6% of the centers, a psychiatric evaluation was ordered only in patients with “known” psychiatric history and another 16% relied on the recommendation of the neuropsychologist. Finally, an additional 45% of centers referred patients for a psychiatric evaluation in either of the two latter circumstances. Clearly, most centers referred patients for psychiatric evaluations based on “partially known” data. Indeed, it is a well-known fact that comorbid psychiatric disorders (past and present) are more often than not under-recognized, be it depression, anxiety or attention-deficit hyperactivity disorder (ADHD) and only the more severe types of psychopathology (i.e., psychosis) are reported to the treating neurologist. Furthermore, neuropsychological evaluations are ideal to identify cognitive disturbances but suboptimal (and often inadequate) to identify comorbid psychopathology, particularly past psychiatric history, as most neuropsychological protocols rely only on screening instruments that detect psychiatric symptomatology during the 2 to 4 weeks preceding the time of completing the questionnaire. As shown in the subsequent text, knowledge of lifetime and family psychiatric history is of the essence in predicting postsurgical psychiatric complications. These data are rarely obtained in neuropsychological evaluations. Furthermore, neuropsychological evaluations are more likely to rely on screening instruments to identify symptoms of depression and anxiety, but more often than not fail to provide a complete psychiatric profile of the patient that may include a lifetime history of their psychiatric disorder.

The relatively low number of centers that perform routine presurgical psychiatric evaluations in all candidates is not surprising, given the lack of available psychiatrists that are part of the epilepsy team. Indeed, among the 47 respondent epilepsy centers, only 25% had a psychiatrist as part of their team and more than 50% of centers relied on different psychiatrists to perform their evaluations. The reliance on a different psychiatrist to conduct the evaluations has important “negative” implications on the quality of these evaluations, as the level of expertise on psychiatric issues of epilepsy and in particular, of epilepsy surgery, varies widely among these psychiatrists. A consequence of this inconsistent pattern of presurgical psychiatric evaluations and the paucity of available reliable data is the lack of consensus among these 47 centers on the risk that patients undergoing an ATL have of experiencing postsurgical psychiatric complications: 45% thought that such risk existed, whereas 55% did not. Interestingly enough, the epilepsy centers that counted with a psychiatrist in their epilepsy team were significantly more likely to be concerned about such risk.

Clearly, these data show the lack of consensus on the potential for postsurgical psychiatric complications among the “top” epilepsy centers in the world and by itself, are indicative of the urgent need to begin systematic psychiatric presurgical evaluations to identify the circumstances under which these types of evaluations are of the essence.

Postsurgical Psychiatric Complications

Despite the fact that postsurgical complications have been recognized since the beginning of epilepsy surgery, there have been very few studies that have evaluated the postsurgical psychiatric complications and their risk factors in a systematic and methodologically sound manner. For a long time, much of the available data were obtained from the case series of temporal lobectomies carried out at the Guy-Maudsley Hospital in London (11). However, in the last decade new case series have been published from various epilepsy centers. The most frequent complications include: (i) depressive disorders with and without anxiety, and (ii) psychosis. Less frequent complications have included the de novo development of psychogenic nonepileptic events (PNEE) and other types of somatoform disorders. These will be reviewed in the subsequent text in some detail.

Postsurgical Depressive and Anxiety Disorders

Characteristically, postsurgical psychiatric complications presenting as depressive and anxiety episodes occur within the first 12 months of the surgery, with a higher symptom incidence in the first 6 months. Yet, a careful review of the available literature suggests that such symptomatology is an expression of a recurrence or exacerbation of presurgical depressive and/or anxiety disorders, although de novo mood/anxiety disorders are significantly less frequent (see subsequent text). Several case series have shown that postsurgical depressive disorders are quite common, although the prevalence rates vary widely among the different studies from a low rate of 5% up to 63%, with a mean of 26%. In a study of 274 patients, Bruton et al. found a 20-fold increase in prevalence of depression after surgery (12). Furthermore, postsurgical mood disorders can vary in severity from mild dysphoric episodes to major depressive episodes associated with suicidal attempts.

Prevalence Rates, Course and Risk Factors

Postsurgical mood changes can be identified early in the course of the postsurgical period. For example, Wrench et al. investigated the occurrence of mood disorders in 62 patients, 43 who underwent an ATL and 17 an ETL (13). Psychiatric status was evaluated at the time of discharge, at 1 month and 3 months after surgery. The presurgical histories of depression and anxiety were comparable between the two groups (33% and 23% respectively for ATL and 53% and 18% respectively for ETL). At 1 month after surgery, symptoms of anxiety and/or depression were reported by 66% of patients who underwent ATL versus 19% of patients who underwent ETL. At 3 months, 54% of the patients who underwent ATL were still symptomatic versus 33% of patients who underwent ETL, with 30% of those who underwent ATL and 17% of those who underwent ETL still experiencing a depressive episode. Furthermore, at the 3-month evaluation 13% of patients who underwent ATL had developed a de novo depression and 15% a de novo anxiety disorder, whereas 18% had developed other type of de novo psychopathology. In contrast, only 17% of patients who underwent ETL had developed de novo anxiety, but not depression or other psychopathology. At 3 months’ follow-up, there was no significant association between postsurgical psychopathology and seizure outcome. Similar findings were reported by Ring et al. in a study of 60 consecutive patients who underwent an ATL (14) and had a psychiatric evaluation before surgery, at 6 weeks and 3 months after surgery. At 6 weeks, 45% of all patients were displaying emotional lability and reflected a de novo psychiatric complication in half of all patients who were free of any comorbid psychopathology presurgically. By 3 months, the emotional lability and symptoms of anxiety had remitted or improved significantly but not so the depressive states.

Surgery appears to lower the presurgical prevalence rates of depression and anxiety disorders, but does not eradicate these disorders. Therefore, Altshuler et al.
followed up 49 consecutive patients who had undergone an ATL for 10.9 years postsurgically (15); 17 of these patients (35%) had a lifetime history of at least one major depressive episode. Eight of these patients (47%) never experienced another major depressive episode postsurgically, although nine (53%) did. In addition, five patients (10%) developed a de novo depressive episode, four within the first postoperative year. Therefore, epilepsy surgery was followed by a decrement of the prevalence rate of depression by 50% in patients who were symptomatic presurgically. In this study, the only predictor for postsurgical depressive disorder was a presurgical history of depression. Glosser et al. (16) carried out a psychiatric evaluation as part of a presurgical evaluation in 44 patients who underwent an ATL; 39 were available for repeat psychiatric evaluation 6 months after surgery and 51% met a Diagnostic and Statistical Manual for Mental Disorders, Third Edition, Revised (DSM-III-R) diagnosis before surgery, with depression and anxiety disorders accounting for most of the psychopathology identified. In the first month after surgery, 12 patients (31%) developed de novo depression and/or anxiety disorders or recurrence of a disorder that had been in remission during the 6 months preceding the surgical procedure. By 6 months, they were still symptomatic but significantly improved and by 1 year, all but two patients had become free of symptoms. By the same token, six patients (15%) who were symptomatic before surgery became asymptomatic postsurgically. Twenty-one patients had no change in their psychiatric status: 8 who were symptomatic and 13 who were asymptomatic before surgery. Although the overall prevalence of psychiatric disorders had not changed 6 months after surgery, the symptom severity measured with the Brief Psychiatric Rating Scale had improved significantly. Right temporal seizure foci were associated with a higher frequency of mood disorders before, but not after surgery.

In a study of 50 consecutive patients who underwent epilepsy surgery (44 had an ATL and 6 a frontal lobe resection), Blumer et al. carried out a psychiatric evaluation before surgery and 2 years after surgery (17). They found an interictal dysphoric disorder (IDD) in 25 (57%) of the 44 patients who had an ATL presurgically. After surgery, 14 patients (32%) developed de novo psychiatric disorders presenting as IDD in 6 patients, depressive episodes in 2 patients, and a psychotic disorder in 6 patients, although 3 patients (7%) experienced an exacerbation of a presurgical IDD. In all but two patients, the psychiatric complications occurred within 2 months of surgery. These authors related the psychiatric complications to the persistence of seizures after the surgery. All psychiatric complications remitted with psychotropic treatment.

Devinsky et al. reported the results of a study that evaluated changes in depression and anxiety 2 years after surgery in 360 patients from seven epilepsy centers in the United States who underwent epilepsy surgery; 89% had an ATL (18). An Axis I diagnosis was established at both points in time with the structured interview, Composite International Diagnostic Interview. Presurgically, 75 patients (22%) met the criteria for a diagnosis of depression, 59 (18%) of anxiety disorders and 12 (4%) of other psychiatric disorders including bipolar illness and schizophrenia. At the 2-year postsurgical evaluations, only 26 patients (9%) met the criteria for depression and 20 (10%) for anxiety, whereas 3 patients (1%) met the criteria for other Axis I diagnosis. De novo symptoms of depression and anxiety were reported by 6.1% and 6.9% of patients, respectively. In this study, the presence of an anxiety or depressive disorder postsurgically was not associated with seizure outcome.

Kanner et al. carried out a psychiatric evaluation as part of the presurgical workup of 97 consecutive patients who underwent an ATL at the Rush Epilepsy Center and investigated the postsurgical seizure outcome, psychiatric complications, and change in employment status (19). Patients were followed up for a mean period of 6.8 ± 2.9 years after surgery. Among these 97 patients, 60 (61%)
had MTS, 18 (18.6%) lesional TLE and 19 (19.6%) idiopathic TLE. Fifty-five patients (57%) had a lifetime psychiatric history before surgery, most of which consisted of depression alone in 22 patients, and mixed depression and anxiety disorder in 25. Eight patients had other psychiatric disorders, most of which included ADHD. Postsurgical psychiatric complications included 11 patients (11.3%) with de novo depressive disorder and 3 patients (3%) with de novo psychosis, although 7 patients (7.2%) developed de novo psychogenic nonepileptic events. Among the 47 patients with a presurgical history of depressive, with or without anxiety, disorders, 27 (28%) experienced an exacerbation in severity during the first 12 months after surgery. At the last contact, 13 patients (13.5%) were symptomatic and their psychiatric disorder had failed to remit despite multiple pharmacological trials. Univariate analyses identified persistent seizures, presurgical psychiatric history, and a left temporal seizure focus as predictors of postsurgical psychiatric complications. Multivariate regression models, however, identified only a presurgical history of depression as a predictor of postsurgical psychiatric complications, with side of the seizure focus yielding only a statistical trend. Interestingly enough, having obtained gainful employment after surgery was not a predictor of postsurgical psychiatric complications.

Quigg et al. studied the relationship between the laterality of the seizure focus and the risk of depression before surgery and 1 year postsurgically among 107 patients, 90 of whom underwent an ATL and 17 an ETL (20). They used the Scale 2 of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a Clinical Depression Index (CDI), psychiatric referral, or attempted/completed suicide to assess psychiatric symptomatology. Outcome at 1 year was modeled by regression techniques as functions of preoperative mood measurements, side of epilepsy surgery, and preoperative verbal intelligence. Higher presurgical depressive comorbidity and right-sided surgery were significant predictors of more severe postoperative depressive symptoms measured with the CDI. Higher preoperative Scale 2 scores, indicating worse depressive traits, predicted worse postoperative Scale 2 scores. Although the side of surgery did not predict higher Scale 2 scores, there was a trend for the Scale 2 scores of patients with preoperative right-sided foci to have higher postsurgical scores. Findings for the temporal lobectomy subgroup (n = 90) were similar to those of the overall sample. The authors concluded that patients undergoing right hemispheric epilepsy surgery, especially those with high presurgical depression-related morbidity, might be particularly susceptible to clinical depression. However, these findings were not replicated by Helmstaedter et al. These investigators examined the interaction of depressive mood and memory as a function of lateralization of the seizure focus (21) in 152 patients with TLE, 68 with right temporal foci and 84 with left temporal foci. Depressed mood established with a score greater than 12 in the Beck Depression Inventory was found in 30% of all patients, and there was no difference among patients with left or right foci.

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