Epilepsy surgery in tuberous sclerosis complex: Emphasis on surgical candidate and neuropsychology

Purpose: To discuss neuropsychological outcome and candidate of epilepsy surgery for tuberous sclerosis complex (TSC). Methods: To retrospectively analyze clinical data of 25 patients with TSC and epilepsy who underwent epilepsy surgery between 2001 and 2007. Seizure reduction was analyzed at 1‐year (1FU), 2‐year (2FU), and 5‐year (5FU) follow‐up visits after surgery, and outcomes of intelligence quotient (IQ) and quality of life (QOL) were evaluated at 2FU. Results: Resective procedures included 14 tuber resections, 9 lobectomies, and 2 tuber resections and lobectomies. Corpus callosotomies (CCTs) were performed as the adjunctive approach in eight cases with low IQ and behavioral problems. The percentages of seizure‐free cases were 72% at 1FU, 60% at 2FU, and 54.5% at 5FU, and the factors predicting seizure freedom included the course of seizures and ages of patients. Significant improvement was found in performance IQ in patients with preoperative low IQ or CCT. Significant improvement in mean QOL score was observed in all patients, especially patients with preoperative low IQ and CCT but postoperative seizure freedom. Conclusion: To be surgical candidates, patients with TSC and epilepsy should have identified epileptogenic tubers, and candidates should include patients with low IQ and multiple epileptogenic tubers. Satisfactory seizure control was often achieved with early operation, whereas improved QOL was observed frequently in postoperative seizure‐free patients. CCT could be performed as an adjunctive approach to resective operation for TSC patients with epilepsy and low IQ and render improvement of performance IQ and QOL.     

Resective surgery for intractable focal epilepsy in patients with low IQ: predictors for seizure control and outcome with respect to seizures and neuropsychological and psychosocial functioning

PURPOSE: To investigate possible predictive factors for seizure control in a group of children and adults with low IQs (IQ, < or =70) who underwent resective surgery for intractable focal epilepsy and to study outcome with respect to seizures and neuropsychological functioning. We also studied psychosocial outcome in the adult patients. METHODS: Thirty-one patients (eight children younger than 18 years) with a Wechsler Full Scale IQ of 70 or less underwent comprehensive neuropsychological assessments before and 2 years after surgery. Adults also completed the Washington Psychosocial Seizure Inventory (WPSI). Univariate analyses were used to identify variables differentiating between patients who became seizure free and those who did not. Pre- and postoperative test results were compared by t test for dependent samples. RESULTS: Forty-eight percent of the patients became seizure free, 52% of those with temporal lobe resection and 38% of those with extratemporal resection. Only one variable was predictive for seizure outcome: duration of epilepsy. In one third of the patients, who had the shortest duration of epilepsy (<12 years), 80% became seizure free. Significant improvement was seen regarding vocational adjustment in adults (WPSI). Seizure-free adults improved their Full Scale IQ scores. No cognitive changes were found in seizure-free children or in patients who did not become seizure free. CONCLUSIONS: A good seizure outcome was obtained after resective surgery in patients with intractable focal epilepsy and low IQ, provided that treatment was done relatively shortly after onset of epilepsy. No adverse effects were seen on cognitive and psychosocial functioning.     

Preoperative IQ predicts seizure outcomes after anterior temporal lobectomy

PurposeIQ tests are frequently used in the preoperative neuropsychological assessment of candidates for anterior temporal lobectomy (ATL). We reviewed IQ test results and surgery outcomes to evaluate the roles of IQ tests in the preoperative work-up.MethodsA total of 205 adult patients who had undergone ATL and whose seizure outcomes were followed for 2 years after surgery were included. The short form WAIS-R was used to estimate intelligence. Multiple linear regression and logistic regression analyses were used to examine the variables for IQ and seizure outcomes.ResultsEducation, duration of epilepsy and gender were factors that accounted for 24.6% of the variance in the full-scale IQ (FSIQ) scores. The verbal IQ and performance IQ discrepancies at various magnitudes could not lateralize the seizure foci. Freedom of seizure was noted in 128 (62.4%) of the patients. Seizure outcomes, however, correlated with the preoperative FSIQ. After adjustment for variables that affect seizure outcomes, the FSIQ was an independent predictor of postoperative seizure outcomes (OR 1.04, 95% CI 1.01–1.06, p = 0.003). Of patients who had FSIQ lower than 70, 50% became free from seizures by 2 years after surgery.ConclusionsIn our study, IQ tests were unable to lateralize seizure foci but may serve as an independent predictor of postoperative seizure outcomes. Since a longer duration of epilepsy had deleterious effects on intelligence, earlier surgical intervention might better preserve neuropsychological function and, consequently, allow better seizure control after ATL. Nonetheless, patients with lower IQ scores could still benefit from ATL.     

Multivariate neuropsychological prediction of seizure lateralization in temporal epilepsy surgical cases

PURPOSE: Neuropsychological assessment can be of assistance in determining seizure lateralization in cases where EEG and MRI findings do not provide clear lateralizing data. While several studies have examined the lateralizing value of individual neuropsychological measures, clinicians are still in need of a statistically sound method that permits the incorporation of multiple neuropsychological variables to predict seizure lateralization in the individual patient. METHOD: The present study investigated the lateralizing value of several commonly used neuropsychological measures in a large sample of patients (n = 217) who eventually underwent surgical resection to treat their epilepsy. Side of surgery was used to operationally define seizure lateralization. A comparison of the relative utility of a multivariate versus univariate approach to predict seizure lateralization was conducted in temporal epilepsy cases. RESULTS: The results provide evidence for the incremental validity of neuropsychological measures, other than memory and IQ tests, in the prediction of seizure lateralization in patients with medically intractable epilepsy. These data indicate that a multivariate approach increases the accuracy of prediction of seizure lateralization for temporal lobe epilepsy cases. CONCLUSION: This study supports the use of a multivariate approach using neuropsychological measures to predict seizure lateralization in temporal epilepsy surgical candidates. Regression formulas are provided to enhance the clinical utility of these findings.     

Long-term outcomes of epilepsy surgery in tuberous sclerosis complex

Approximately 50% of patients with tuberous sclerosis complex (TSC) present intractable epilepsy, and surgery is an option for those patients. Hereby, we analyze long-term seizure control and neuropsychological outcomes of epilepsy surgery in patients with TSC. Clinical data were retrospectively collected from 66 patients with TSC and epilepsy followed up over 5 years, 51 of whom underwent epilepsy surgery between 2001 and 2011. Reductions in the number of seizures were analyzed at 1-year (1FU), 5-year (5FU), and 10-year (10FU) follow-ups visits after the operation. Influential factors on postoperative seizure free and intelligence quotient (IQ) and quality-of-life (QOL) outcomes were evaluated at 5FU. Resective procedures included 26 tuber resections, 15 lobectomies, and 10 tuber resections and lobectomies. Corpus callosotomies were performed as the adjunctive approach in 11 cases with low IQ. The percentages of seizure-free cases were 74.5% at 1FU, 58.8% at 5FU, and 47.8% at 10FU, and the predictive factor for long-term postoperative seizure freedom was the history of preoperative seizures and preoperative full-scale IQ. Significant improvements were found in performance IQ, full-scale IQ, and QOL in patients from the surgery group, particularly those who were seizure free after the operation. Our study showed that epilepsy surgery in TSC with epilepsy rendered improvements in seizure control, full-scale IQ, and QOL. Satisfactory long-term seizure control was often achieved with an early operation and without mental retardation, and improvements in QOL and IQ were frequently observed in postoperative patients who remained seizure free.     

Does Presurgical IQ Predict Seizure Outcome After Temporal Lobectomy ? Evidence from the Bozeman Epilepsy Consortium

Summary: Purpose: Considerable debate exists Concerning whether the presence of low preoperative IQ should be a contraindication for focal resective epilepsy surgery.
Methods: We examined the relationship between baseline IQ scores and seizure outcome in 1,034 temporal lobectomy cases from eight epilepsy surgery centers participating in the Bozeman Epilepsy Consortium.
Results: Those patients who continued to have seizures following surgery had statistically lower preoperative IQ scores than those who were seizure-free (p < 0.009), but only by 2.3 points. This small but statistically significant relationship was fairly robust; it was observed across seven of the eight centers, and indicates that the findings can be generalized. Among patients with IQ scores of ≤75, 32.8% continued to have seizures following surgery, whereas 23.8% and 16.9% were not seizure-free when IQ scores were between 76 and 109 and ≥110, respectively. Relative risk analyses revealed no significant increase in risk among patients with low IQ scores who had no structural lesions other than mesial temporal sclerosis. However, patients with IQ scores of ≤75 had nearly a fourfold (390%) increase in risk for continued seizures as compared with those with higher IQ scores if structural lesions were present.
Conclusions: While our results suggest that preoperative IQ scores alone are not good predictors of seizure outcome and should not be used to exclude patients as potential surgical candidates. IQ scores can be useful for counseling patients and their families concerning the relative risks of surgery.     

Cognitive outcome of parietooccipital resection in children with epilepsy

Purpose: We followed the neuropsychological development of five children who underwent unilateral neurosurgery of the occipitoparietal lobes as a treatment for epilepsy caused by a developmental lesion (cortical dysplasia). Methods: The follow‐up period ranged from 3–7 years postsurgery. Results: Two participants had a verbal intelligence quotient (IQ) >100 and three had a verbal IQ between 65 and 80. All five children had abnormal nonverbal IQ and exhibited deficits related to visual attention, object recognition, and praxis. Nevertheless, our results suggest that brain plasticity after parietooccipital epilepsy surgery in young children allows for a schooling level of cognitive skills such as reading and arithmetic. Discussion: Although recovery for visual perceptual cognition was more limited than for verbal functions, long‐term neuropsychological outcomes showed that early surgery for epilepsy offers the possibility of optimizing cognitive outcomes in children with posterior intractable epilepsies.     

Hidden learning disability

Although it has been suggested that about 2.5% of the population as a whole should be regarded as having a mild‐to‐moderate learning disability, only about 0.25% of the population is registered as having a learning disability. This paper considers why this disparity exists. It is suggested that although 2.5% of the population may be a good estimate for people with IQs less than 70, a better estimate of the proportion of the population who reach a dual criteria of having both a low IQ and social/skill defects is about 1%. It is pointed out that even if true prevalence rate of learning disability is nearer to 1% rather than 2.5%, services still only know of a small proportion of people who could be considered to have a learning disability, and there are probably a large number of people with unidentified learning disabilities. It is also noted that the term ‘learning disability’ can be very confusing as it is not clear if it refers to people who have IQs below 70, people with both intellectual and adaptive disabilities or people who have been given a learning disability label. The implications of this for services and research are discussed.     

Seizure control and mortality in epilepsy.

Mortality rates are increased among people with epilepsy, and may be highest in those with uncontrolled seizures. Because epilepsy surgery eliminates seizures in some people, we used an epilepsy surgery population to examine how seizure control influences mortality. We tested the hypothesis that patients with complete seizure relief after surgery would have a lower mortality rate than those who had persistent seizures. Three hundred ninety-three patients who had epilepsy surgery between January 1986 and January 1996 were followed after surgery to assess long-term survival; 347 had focal resection or transection, and 46 had anterior or complete corpus callosotomy. A multivariate survival analysis was performed, contrasting survival in those who had seizure recurrence with survival of those who remained seizure free. Standardized mortality ratios and 95% confidence intervals were calculated. Overall, seizure-free patients had a lower mortality rate than those with persistent seizures. This was true for the subset of patients with localized resection or multiple subpial transection. No patients died among 199 with no seizure recurrence, whereas of 194 patients with seizure recurrence, 11 died. Six of the deaths were sudden and unexplained. Most patients who died had a substantial reduction in postoperative seizure frequency. The standardized mortality ratio for patients with recurrent seizures was 4.69, and the risk of death in these patients was 1.37 in 100 person-years, whereas among patients who became seizure free, there was no difference in mortality rate compared with the age- and sex-matched population of the United States. Elimination of seizures after surgery reduces mortality rates in people with epilepsy to a level indistinguishable from that of the general population, whereas patients with recurrent seizures continue to suffer from high mortality rates. This suggests that uncontrolled seizures are a major risk factor for excess mortality in epilepsy. Achieving complete seizure control with epilepsy surgery in refractory patients reduces the risk of death, so the long-term risk of continuing medical treatment appears to be higher than the risk of epilepsy surgery in suitable candidates.     

Clinical guidelines for the management of epilepsy in adults with an intellectual disability

Clinical guidelines exist for the treatment of chronic epilepsy and epilepsy in women (2). This publication provides guidance for the clinician investigating and managing epilepsy in adults who have an intellectual disability as defined by an Intelligence Quotient (IQ) of less than 70, onset in the developmental period and difficulties with adaptive functioning.     

Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults

In our first paper in this series (Epilepsia 2015; 56(5): 674–681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence‐based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long‐term assessment of these changes following surgery should form an integral part of the postoperative follow‐up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.     

The early identification of candidates for epilepsy surgery

The effectiveness of resective surgery for the treatment of carefully selected patients with medically intractable, localization-related epilepsy is clear. Seizure-free rates following temporal lobectomy are consistently 65% to 70% in adults and 68% to 78% in children. Extratemporal resections less commonly lead to a seizure-free outcome, although one recent childhood series reported a seizure-free rate of 62% following extratemporal epilepsy surgery. With both temporal and extratemporal resections, additional patients have a reduction in seizures following surgery but are not completely seizure free. The identification of favorable surgical candidates has been the subject of extensive research, and many investigators have examined predictors of outcome following epilepsy surgery. However, the early identification of the potential epilepsy surgery candidate and the optimal timing of surgery have only occasionally been addressed in the literature. This issue is methodologically challenging to study since studies require large numbers of patients with new-onset partial epilepsy who are followed over time. The purpose of this article is to review the current ability for early prediction of medical intractability in patients with surgically remediable epilepsy. Emphasis will be placed on the early prediction of intractable temporal lobe epilepsy in children and adolescents, since temporal lobectomy remains the prototype epilepsy surgery, and early surgery may improve psychosocial outcome in younger patients.     

Cognitive skills in children with intractable epilepsy: comparison of surgical and nonsurgical candidates

PURPOSE: To compare neuropsychological performance of two groups of children with intractable epilepsy: those who are surgical candidates, and those who are not. METHODS: Intelligence, verbal memory, visual memory, academic skills, and sustained attention were measured in children aged 6-18 years. The effects of number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset, and duration of seizure disorder were examined. RESULTS: Both groups had high rates of impairment. Group differences were found only on the verbal memory task. Children who experienced seizures in clusters had higher IQ, reading comprehension, and arithmetic scores. Age at seizure onset and proportion of life with seizures were related to IQ. Performance did not vary with AED monotherapy versus polytherapy. CONCLUSIONS: Few differences exist in cognitive performance between children with intractable seizures who are and those who are not surgical candidates. These findings suggest that children who are not surgical candidates can serve as good controls in studies on cognitive outcome of surgery.     

Academic achievement one year after resective epilepsy surgery in children

PurposeFew studies have examined the academic functioning of children following pediatric epilepsy surgery. Although intellectual functioning has been more thoroughly investigated, children with epilepsy may experience additional difficulties with academic skills. This study examined the academic outcomes of a cohort of children who underwent pediatric epilepsy surgery on an average 1.2 (standard deviation [SD]: 0.3) years prior.MethodsParticipants were 136 children (mean age: 14.3 years, [SD]: 3.7 years) who had undergone resective epilepsy surgery. Academic functioning was assessed presurgery and postsurgery using standardized tests of reading, reading comprehension, arithmetic, and spelling.ResultsAt baseline, 65% of the children displayed low achievement (1 SD below test mean), and 28% had underachievement (1 SD below baseline IQ) in at least one academic domain. Examining change over time revealed that reading, numeral operations, and spelling significantly declined among all patients; seizure freedom at follow-up (attained in 64% of the patients) did not influence this relationship. Reading comprehension and IQ remained unchanged. Similar findings were found when examining patients with a baseline IQ of ≥ 70 and when controlling for IQ. Regression analyses revealed that after controlling for IQ, demographic and seizure-related variables were not significantly associated with academic achievement at follow-up.ConclusionsResults show baseline academic difficulties and deteriorations following surgery that go beyond IQ. Further investigations are required to determine whether the observed deteriorations result from the development of the child, the course of the disorder, or the epilepsy surgery itself. Long-term studies are warranted to identify the progression of academic achievement and whether the observed deteriorations represent a temporal disruption in function.     

Reexamining the effects of epilepsy surgery on IQ in children: use of regression-based change scores.

Prior studies have found no adverse effects of pediatric epilepsy surgery on IQ. However, empirical techniques such as regression models, designed to account for confounding factors such as practice effects and test-retest reliability and able to provide a standardized method for evaluating outcome, have not been used in studying change after pediatric epilepsy. The goal of this study was to demonstrate the regression technique while empirically measuring the effect of epilepsy surgery on IQ in a group of pediatric patients. Predictors of retest IQ (e.g., baseline IQ, retest interval, demographics, epilepsy severity) were evaluated in a control group with intractable seizures (N = 23) assessed twice with the WISC-III. The resulting equation was used to evaluate IQ changes in a second group of children who underwent epilepsy surgery (N = 22). In controls, baseline IQ was a strong predictor of retest IQ. Number of AEDs was inversely related to retest IQ. Based on the control regression, four children (18%) in the surgical sample obtained significantly higher than expected postsurgical IQ scores and one child (5%) obtained a lower than expected IQ score. This study demonstrates that regression-based techniques yield informative estimates on outcome and may be an improvement over prior methods of measuring change after pediatric epilepsy surgery.     

Postsurgical changes in self-reported mood and Composite IQ in a matched sample of patients with frontal and temporal lobe epilepsy.

Changes in self-reported mood assessed by the Beck Depression Inventory (BDI) were examined in a sample of 60 left-hemisphere speech-dominant patients who underwent epilepsy surgery (15 right frontal, 15 left frontal, 15 right temporal, 15 left temporal). Temporal lobectomy patients were matched to frontal lobectomy patients by presurgical BDI scores, premorbid K-BIT composite IQ, sex, age, and years since seizure onset. Overall, self-reported mood improved following surgery, with men showing a greater improvement than women. There were no differences among the four groups in terms of pre-surgical and post-surgical reported mood. However, frontal patients showed more extreme changes in mood in either direction than temporal patients. Additionally, while temporal patients showed gains in Composite IQ, no such gains were observed in frontal patients. Changes in mood in frontal patients were not related to postsurgical seizure outcome or time since surgery, but were related to changes in Composite IQ.     

Postsurgical Changes in Self-Reported Mood and Composite IQ in a Matched Sample of Patients With Frontal and Temporal Lobe Epilepsy

Changes in self-reported mood assessed by the Beck Depression Inventory (BDI) were examined in a sample of 60 left-hemisphere speech-dominant patients who underwent epilepsy surgery (15 right frontal, 15 left frontal, 15 right temporal, 15 left temporal). Temporal lobectomy patients were matched to frontal lobectomy patients by presurgical BDI scores, premorbid K-BIT composite IQ, sex, age, and years since seizure onset. Overall, self-reported mood improved following surgery, with men showing a greater improvement than women. There were no differences among the four groups in terms of pre-surgical and post-surgical reported mood. However, frontal patients showed more extreme changes in mood in either direction than temporal patients. Additionally, while temporal patients showed gains in Composite IQ, no such gains were observed in frontal patients. Changes in mood in frontal patients were not related to postsurgical seizure outcome or time since surgery, but were related to changes in Composite IQ.     

Level and pattern of neuropsychological functioning in early-onset psychoses

The present study aimed to compare the level and pattern of cognitive deficits in patients with early-onset psychoses with an age, gender and IQ matched control group. In order to ensure a representative sample of patients with psychoses, participants with an IQ of less than 70 were included. Forty-eight patients with an onset of psychoses before the age of 16, and 47 age, gender and IQ matched controls without psychoses were recruited. Psychotic symptomatology was assessed using the Schedules for Clinical Assessment to obtain DSM-IV and ICD-10 diagnoses. Positive and negative symptoms were assessed using the Positive and Negative Symptoms Scale. Levels of cognitive function were measured using a comprehensive neuropsychological battery. A pattern of specific impairments was not found, with few significant differences between the two cohorts. However both cohort groups performed lower than age derived norms. Therefore it appears that there are global cognitive deficits rather than specific deficits in early-onset psychoses when compared to normative data, in-line with conclusions of early-onset schizophrenia research, but patients did not have greater deficit than controls when matched on IQ, gender and age, even after excluding participants with IQ less than 70.     

Are there physical risk factors for psychogenic non-epileptic seizures in patients with epilepsy?

Patients with epilepsy may have additional psychogenic non-epileptic seizures (PNES). It has been suggested that PNES are more common if patients with epilepsy are female, develop epilepsy later in life and have right-sided brain lesions. We examine whether these or other physical factors affect the risk of PNES in patients with epilepsy in a controlled study. METHODS: Ninety consecutive patients with PNES and concurrent epilepsy (PNES+E group) and 90 consecutive patients with epilepsy alone (epilepsy group) were compared with regard to the variables sex, age at onset of epilepsy, epilepsy type (focal/generalised), location and lateralisation of epileptogenic zone, aetiology of epilepsy, interictal epileptiform potentials, magnetic resonance imaging (MRI) abnormalities, neuropsychological (NPS) deficits and intelligence quotient (IQ). RESULTS: Female sex (P<0.001), abnormal visual memory (P=0.012), global NPS impairment (P=0.029), and low IQ category (P=0.005) were associated with a higher risk of PNES. Other variables did not differ between the groups. CONCLUSIONS: In patients with epilepsy, female sex, poor visual memory or global neuropsychological underperformance and low IQ are associated with an increased risk of PNES. MRI changes, epileptiform EEG abnormalities and location of epileptogenic zone do not show a predilection for one hemisphere.     

Victoria symptom validity test performance in non-litigating epilepsy surgery candidates

We report Victoria Symptom Validity Test (VSVT) performance in 120 epilepsy patients undergoing neuropsychological assessment as part of their evaluation as epilepsy surgery candidates. Patients were grouped according to their performance on hard VSVT stimuli. Scores of at least 21/24 on the hard VSVT items were classified as valid (n=86), scores of 18/24-20/24 were considered questionably valid (n=20), and scores of 17/24 and below were designated as invalid (n=14). Significant group effects were observed for WAIS-III Full Scale IQ, Verbal IQ, Performance IQ, Digit Span, Rey 3x5 Memory, Selective Reminding Recognition, and Complex Figure Immediate Recall; poorer cognitive scores were associated with lower VSVT scores. Age was also related to VSVT performance, with patients older that 40 years of age (16/42) more likely to fail the VSVT (i.e., hard scores < or = 20/24) than their younger counterparts (8/78) (p=.0006, Fisher's Exact Test). These results indicate that VSVT may identify cases of incomplete effort in patients being evaluated for strictly clinical purposes in which no external incentive to perform poorly has been identified, although the potential confound of low IQ on VSVT cannot be determined from this sample. Older patients also appear to be at increased risk for suboptimal performance, and may need additional encouragement or education regarding the need to perform to the best of their ability, and thereby maximize the likelihood of obtaining valid neuropsychological test results.