Jessica S. Chapin

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

Comparison of personality traits in patients with frontal and temporal lobe epilepsies

The current study sought to characterize and compare personality traits of patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). Ninety-seven adults with medically intractable epilepsy (TLE n=58, FLE n=39) completed the Personality Assessment Inventory (PAI) as part of routine preoperative investigations. Not surprisingly, both epilepsy groups endorsed significantly more symptoms across PAI clinical scales than the normative sample, most notably on scales assessing Depression and Somatic Complaints. Direct comparison of personality profiles of people with FLE and TLE revealed that FLE was associated with relative elevations on scales assessing emotional lability and relationship difficulties (i.e., Mania, Borderline Features, Antisocial, Stress, and Nonsupport). Although effect sizes were moderate to large, the clinical significance of these differences was questionable (<1 SD). However, results of a logistic regression suggested that the Borderline Features and Anxiety scales have incremental validity in predicting seizure site (FLE vs TLE) above education and duration of recurrent seizures. These results suggest that patients with FLE may exhibit more behavioral traits associated with frontal dysfunction than patients with TLE.

Seizure semiology and aging

The incidence of epilepsy is high in older individuals. However, epilepsy in the elderly may be underdiagnosed and undertreated because of diagnostic difficulties. The main goal of this study was to determine whether seizure semiology differs between older and younger adults with epilepsy in the outpatient setting. Fifty patients with focal epilepsy aged 55 years and older and 50 patients aged between 18 and 45 years were included. Review of medical records contained detailed seizure description. There were no differences in seizure semiology between groups, except that subtle perceptions of transient confusion were seen in older patients but not in younger patients (P=0.0028). Older patients had less generalized motor seizures, but the differences between groups did not reach significance (P=0.01). Older patients may present with subtle symptoms of seizures characterized by brief periods of confusion, which may contribute to greater difficulty diagnosing seizures in the elderly.

Pre-Surgical Mood Predicts Memory Decline after Anterior Temporal Lobe Resection for Epilepsy

This study examined pre-surgical depressed mood as a predictor of post-surgical memory change in adults who underwent temporal lobe resections (TLRs; n = 211). Patients completed the Wechsler Memory Scale-III and Beck Depression Inventory-Second Edition (BDI-II) before and after TLR (left = 110, right = 101) and were divided into two groups (clinically elevated depressive symptoms or not depressed) based on BDI-II score. Left-TLR patients with poorer pre-surgical mood had greater verbal memory declines after surgery compared with nondepressed left- or right-TLR patients and right-TLR patients with poor mood. Further, pre-surgical BDI-II score demonstrated incremental validity in predicting post-surgical memory change in left-TLR patients beyond pre-surgical memory scores. Differences in seizure outcome and post-surgical mood change could not account for memory decline. Results suggest that elevated pre-surgical depressive symptomatology is a risk factor for post-surgical memory decline and indicate that mood should be considered when advising patients about cognitive risks associated with temporal lobectomy. Results are discussed in terms of poor pre-surgical mood as an indicator of reduced cognitive reserve.

Executive functioning and depressed mood before and after unilateral frontal lobe resection for intractable epilepsy

Executive dysfunction occurs in a variety of patients who have sustained damage to the frontal lobes. In individuals with frontal lobe epilepsy (FLE) or after unilateral frontal lobe resection (FLR), a unique neuropsychological profile linking executive functions (EF) with the frontal lobe has been elusive, with conflicting findings in the literature. Some studies show greater risk of executive impairment with left-sided FLE or FLR, while others report greater risk for right-sided patients. Some studies report no relationship between FLE and EF impairment, while others show EF impairment regardless of side of seizure foci or surgery. In patients with temporal lobe epilepsy, executive dysfunction is associated with depressed mood possibly reflecting disruption of cortical-limbic pathways and/or frontal-striatal circuitry. Although not previously examined, depression level may affect executive functioning in those with FLE or FLR. We hypothesized that FLE patients with poor mood state would show greater executive dysfunction than FLE patients without poor mood state. The relationship among EF, side of surgery and depressed mood before and 8 months after unilateral FLR was evaluated in 64 patients using validated measures of EF and mood state (Beck Depression Inventory-II). Results indicated that individuals with depressed mood before surgery had greater difficulty on a task of mental flexibility compared to patients without preoperative depressed mood. Further, individuals with depressed mood before surgery had significant increases in perseverative responding and completed fewer categories on a card-sorting task after surgery compared to patients without preoperative depressed mood. Regression analyses showed that among side of surgery, seizure freedom status after surgery and depression status, only pre-surgical depression status explained a significant amount of variance in executive functioning performance after surgery. Results suggest that clinically elevated depressive symptoms before surgery are a risk factor for moderate declines in EF after surgery. Results may be attributable to reduced cognitive reserve in patients with depressive symptoms, or may reflect a common cause attributable to damage to unilateral dorsal and ventral lateral frontal lobe.

The Family Pictures subtest of the WMS-III: Relationship to verbal and visual memory following temporal lobectomy for intractable epilepsy

This study examined the extent to which the Family Pictures (FP) subtest of the Wechsler Memory Scale–Third Edition (WMS-III) is related to verbal memory measures and right mesial temporal integrity. Epilepsy patients who underwent temporal lobectomy did not differ in the extent to which FP scores changed from before to after surgery, although postoperative FP performance was worse in those who underwent right temporal lobectomy than in those who underwent left temporal lobectomy. FP was most strongly related to the Logical Memory subtest from the WMS-III. Results suggest that FP measures both verbal and visual memory and is minimally sensitive to lateralization of temporal lobectomy.

Estimating risk of word-finding problems in adults undergoing epilepsy surgery

Objective: This retrospective, observational study examined the frequency and magnitude of change in naming ability as a function of side/site of epilepsy surgery and identified predictive factors to assist clinicians in identifying patients at low, moderate, or high risk of postoperative naming decline. Methods: A total of 875 adults with pharmacoresistant epilepsy (454 left/421 right; 763 temporal/87 frontal/25 posterior quadrant) met inclusion criteria and completed the Boston Naming Test before and after surgery. Clinically meaningful change in naming ability was assessed using reliable change indices for epilepsy. Demographic, cognitive, and seizure variables were examined to determine factors most predictive of naming decline and to develop a decision tree to assist with clinical decision-making. Results: Naming decline was rare in right-sided resections and did not exceed the level expected by chance (5% overall; 90% confidence interval [CI] ± 2%). Naming decline occurred in 41% (CI ± 5%) of patients after left temporal resection (TLR) compared to 10%–12% (CI ± 10%–19%) in other left-sided surgical groups. A sizable proportion of left TLR patients (17%; CI ± 4%) showed substantial declines in naming (>11 points). Decline following left TLR was related to later age at seizure onset, older age at surgery, and higher preoperative naming ability. These factors correctly predicted naming decline in 68% of patients and were associated with degree of decline following left TLR. A decision tree is provided to assist clinicians in identifying patients at low, moderate, or high risk for postoperative naming declines. Conclusions: In addition to discussions regarding risk for memory decline following left TLR, patients should be counseled about potential decline in word-finding ability.

Cognitive characteristics of PTEN hamartoma tumor syndromes

Purpose:We sought to characterize cognition in individuals with germline PTEN mutations (n = 23) as well as in PTEN mutation–negative individuals with classic Cowden syndrome or Bannayan–Riley–Ruvalcaba syndrome (n = 2).Methods:Twenty-five individuals completed a comprehensive neuropsychological evaluation. One sample t-tests and effect sizes were used to examine differences in participant test scores compared with normal controls. Composite scores were created for each patient within each of the cognitive domains assessed and classified as above average, average, or below average according to normative standards. χ2 analyses compared these classifications to expected proportions in normal control samples.Results:The mean intelligence quotient was in the average range, and the range of intellectual functioning was very wide (from extremely low to very superior). However, in a large subset of patients, scores were lower than expected on measures of motor functioning, executive functioning, and memory recall, suggesting disruption of frontal circuits in these participants.Conclusion:This is the first study to characterize cognition in individuals with PTEN mutations and associated syndromes using a comprehensive neuropsychological battery. Contrary to previous reports suggesting an association with intellectual disability, the mean intelligence quotient was average, and there was a broad range of intellectual abilities. Specific evidence of disruption of frontal circuits may have implications for treatment compliance and cancer surveillance, and further investigation is warranted.Genet Med 2013:15(7):548–553

Predictors of decline in verbal fluency after frontal lobe epilepsy surgery.

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome.

APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

This study examined the relationship between the APOE epsilon4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one epsilon4 allele (n=22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without epsilon4 (43%). These preliminary results demonstrate that APOE epsilon4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms.