APPLIED NEUROPSYCHOLOGY: ADULT, 22: 189–196, 2015 Copyright # Taylor & Francis Group, LLC ISSN: 2327-9095 print=2327-9109 online DOI: 10.1080/23279095.2014.895366
Sensitivity and Specificity of Memory and Naming Tests for Identifying Left Temporal-Lobe Epilepsy Laura Glass Umfleet and Julie K. Janecek Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
Erin Quasney Department of Psychology, Marquette University, Milwaukee, Wisconsin
David S. Sabsevitz Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
Joseph J. Ryan Department of Psychological Science, University of Central Missouri, Warrensburg, Missouri
Jeffrey R. Binder and Sara J. Swanson Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.
Key words:
Boston Naming Test, logical memory, seizure, Selective Reminding Test, specificity, Wechsler Memory Scale
Neuropsychological testing is useful for predicting cognitive outcome following anterior temporal lobectomy (ATL; e.g., Binder et al., 2008) and for determining side Address correspondence to Laura Glass Umfleet, Department of Neurology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226. E-mail: lumfl[email protected]
of seizure focus (e.g., Loring, Hermann, Lee, Drane, & Meador, 2000; Loring et al., 2008). Although many studies have shown that neuropsychological testing is useful for predicting risk for naming and verbal memory decline after epilepsy surgery (e.g., Binder et al., 2008; Sabsevitz et al., 2003) and for detecting differences in cognitive performance between left and right ATL
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patients after surgery (e.g., Chelune, Naugle, Luders, Sedlak, & Awad, 1993; Lee, Yip, & Jones-Gotman, 2002; Sherman et al., 2011), there is more controversy about the usefulness of neuropsychological testing for determining the side of seizure focus (e.g., Akanuma et al., 2003; Loring et al., 2000; Rausch & Babb, 1993; Swanson, 2006). More specifically, while significant differences in verbal memory scores are found in patients following left and right ATL (left ATL patients perform more poorly than right ATL patients) and significant presurgical to postsurgical changes are found in patients following left ATL (e.g., Graydon, Nunn, Polkey, & Morris, 2001; Helmstaedter, Elger, Hufnagel, Zentner, & Schramm, 1996; Hermann, Connell, Barr, & Wyler, 1995), the finding of group differences between left and right ATL candidates preoperatively is less well supported (e.g., Akanuma et al., 2003; Helmstaedter et al., 1996; Rausch & Babb, 1993; Saling et al., 1993). Also, differences in nonverbal memory between left and right ATL patients as well as significant declines in nonverbal memory following right ATL are reported less reliably (e.g., Barr, 1997; Graydon et al., 2001; Hermann, Seidenberg, Schoenfeld, & Davies, 1997; Rausch & Babb, 1993). Mixed findings with respect to preoperative group differences between left and right temporal-lobe epilepsy (TLE) surgery candidates are likely due to multiple factors such as variability in measures used across studies, some of which may lack adequate psychometric characteristics (e.g., sensitivity) in a TLE population. The clinical utility of a test can be determined by examining group differences (e.g., right TLE vs. left TLE) in preoperative scores or by determining the sensitivity and specificity of the instrument. Time constraints limit the number of language and memory tests that can be conducted in a preoperative work-up, which underscores the importance of deriving sensitivity statistics for measures used. There are few studies that have reported sensitivity statistics for verbal tasks (Loring et al., 2000, 2008). For instance, Loring et al. (2008) found that the total recall across learning trials of the Rey Auditory Verbal Learning Test (AVLT; sensitivity ¼ 48%, specificity ¼ 67%) was superior in predicting seizure laterality compared with the California Verbal Learning Test (CVLT; sensitivity ¼ 69%, specificity ¼ 39%) and that the Boston Naming Test (BNT; sensitivity ¼ 58%, specificity ¼ 70%) was superior to the Multilingual Aphasia Examination Visual Naming task (sensitivity ¼ 75%, specificity ¼ 39%). Also, compared with the BNT, the AVLT emerged as the only significant predictor of side of seizure focus using logistic regression. Unfortunately, delayed recall trials of the AVLT and CVLT were not included in the analyses. Loring et al.’s (2000, 2008) research underscores the need for future studies to investigate the sensitivity and specificity of other verbal memory measures.
Research of this nature has been critical for the Common Data Elements Project commissioned by the National Institute of Neurological Disorders and Stroke. This project arose out of the need to standardize data collection across investigators, simplify data aggregation, facilitate development of evidence-based guidelines, and standardize disease characterization and outcome assessment (Loring et al., 2011). Although there are several studies that show support for the Selective Reminding Test (SRT; Buschke, 1973; Buschke & Fuld, 1974) with respect to measuring verbal memory dysfunction in TLE (e.g., Binder et al., 2008; Sabsevitz et al., 2001), there are no known investigations that specifically address its sensitivity and specificity in this population. Previous studies have focused on the relationship between the SRT and pathology variables as well as memory outcome following left ATL. For instance, evidence of a relationship between the SRT and neuroimaging in an epilepsy patient sample has been reported. Using a small sample of individuals who completed the SRT preoperatively, Sass et al. (1990) found a significant relationship between hippocampal pathology (i.e., cell density of CA3 and the hilus) and the Long-Term Retrieval score of the SRT in patients with left TLE. In a second study using a small sample with relatively less hippocampal neuron loss, Sass and coauthors (1995) showed a significant correlation between the cell density of the CA1 of the left hippocampus and the SRT in patients with left TLE. In terms of memory outcome following left ATL, greater declines have been observed with the SRT compared with the Logical Memory subtest (I and II) from the Wechsler Memory Scale (WMS; Wechsler, 1987, 1997, 2009). Also, Wada memory scores were associated with SRT outcome but not with Logical Memory outcome (Sabsevitz et al., 2001). In a study of the utility of functional magnetic resonance imaging (fMRI) language lateralization data for predicting verbal memory decline following left ATL, Binder and coauthors (2008) found that fMRI laterality indexes were stronger predictors of list-learning decline on the SRT than of declines in story memory on Logical Memory. Notably, patients in this study had scores that declined most on the Delayed Recall component of the SRT (55% of the group declined) followed by a smaller number of significant declines in SRT Long-Term Memory Storage (LTS; 45% of the group declined) and Consistent Long-Term Memory Retrieval (CLTR; 33% of the group declined) measures. In contrast to these studies that suggest that the SRT is a sensitive verbal memory measure for epilepsy surgery candidates, Loring, Lee, Martin, and Meador (1988) found minimal utility of the SRT for predicting side of seizure onset. However, these findings were based on a small sample of 16 patients with left TLE and 14 patients with right TLE.
SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY
Overall, previous studies have demonstrated that the SRT is sensitive to decline following left ATL, but studies have not addressed the test’s sensitivity and specificity for predicting the side of seizure focus. The SRT has several advantages including (like the AVLT) being available in the public domain, showing a robust decline after left ATL, and being one of the only tests on which decline can be predicted by preoperative fMRI (Binder et al., 2008). The present investigation examined the six-trial SRT (Buschke & Fuld, 1974), WMS Logical Memory subtest I and II (Wechsler, 1987, 1997, 2009), and the BNT (Kaplan, Goodglass, & Weintraub, 1983) to compare the sensitivity and specificity of these measures for determining side of seizure focus. In addition, the present study included the Delayed Recall trial of the SRT, which previously has not been reported. Although not a main focus of the present study, the WMS Visual Reproduction subtests I and II (Wechsler, 1987, 1997, 2009) and the 7=24 Spatial Recall Test (Rao, Hammeke, McQuillen, Khatri, & Lloyd, 1984) were examined to compare the sensitivity and specificity of these nonverbal memory measures to the side of seizure focus. Based on previous research, we hypothesized that the SRT would be a more sensitive measure of side of seizure focus than the Logical Memory subtest and BNT. Further, considering generally insignificant findings of prior studies, we expected that nonverbal memory measures would not be sensitive to lateralized dysfunction, though it is worthwhile to investigate to determine if group differences can be found using a larger number of participants. We also examined the predictive power of the aforementioned measures to show the contributions of these measures to the classification of side of seizure focus. The results of this study will inform future recommendations of test selection in neuropsychological evaluations of patients with epilepsy.
METHOD Participants Patients were retrospectively selected from series of 177 consecutive referrals with TLE and underwent standardized presurgical neuropsychological testing at the Comprehensive Epilepsy Program at the Medical College of Wisconsin from 1998 to 2013. All patients underwent long-term video electroencephalogram (EEG) monitoring, intracarotid sodium amobarbital (Wada) testing, and magnetic resonance imaging (MRI). Exclusion criteria included: (a) Wechsler Full-Scale IQ (FSIQ) < 70, (b) MRI showing contralateral neuropathology such as tumor, stroke, or mesial temporal sclerosis, (c) bilateral seizure foci based on
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EEG, and (d) Wada results indicating bilateral or right-hemisphere language dominance. This excluded 34 of the 177 patients. Participants included 143 patients, 65 with left TLE and 78 with right TLE. Most participants (90%) underwent anterior temporal-lobe resection (53 left TLE and 75 right TLE). The other 10% who did not undergo temporal-lobe resection had clear right or left temporal-lobe seizure focus based on EEG results. Engel Outcome Classifications (Engel, 1987) for individuals who underwent surgery were as follows: 88 Class I outcome (completely seizure-free), 15 Class II outcome (75% but .05). Effect sizes for these comparisons are also presented in Table 3. Although modest, the SRT Delayed Recall (ES ¼ .55) and BNT (ES ¼ .46) yielded the largest effect sizes. Included in Table 4 are results for group comparisons on visual memory measures. No significant group differences emerged on mean Visual Reproduction I and II and 7=24 Spatial Recall variables. Patient demographic information was not entered as covariates in regression analyses as there were no TABLE 1 Frequencies for Demographic Information for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Variable Sex Male Female Race Caucasian African American Other Handedness Right Left Mixed
Left TLE Frequency
Right TLE Frequency
30 35
38 40
61 2 2
70 6 2
58 5 1
61 9 7
Note. We speculate that there is a higher rate of left and mixed handedness in the right TLE group because a number of the lefthanded individuals with left TLE were removed from the study due to having right-hemisphere language dominance. This syndrome is known as pathological left handedness and occurs when disease or insult to the left hemisphere is associated with left handedness and reorganization of language to the right hemisphere.
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SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY TABLE 2 Demographic Means and Standard Deviations for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Left TLE Variable Age Education Seizure Frequency (# per month) Age at onset of Recurrent Seizures (years) Duration of Seizure Disorder (years) Total # of Seizure Medications Mesial Temporal Sclerosis Full-Scale IQ
TABLE 4 Means, Standard Deviations, and t Test Results for Visual Memory Tasks for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups
Right TLE
Left TLE
M
SD
N
M
SD
N
p
35.28 12.82 14.85
9.97 2.39 24.06
65 64 61
38.46 13.57 22.60
10.83 2.65 43.46
78 77 73
.07 .08 .22
16.62
11.37
64
17.55
11.60
78
.63
19.13
12.97
63
21.20
13.71
78
.36
2.00
0.73
65
1.96
0.81
78
.77
27 94.52
11.60
65
Variable
96.14
11.91
78
.42
TABLE 3 Means, Standard Deviations, and t Test Results for Verbal Memory and Confrontation Naming Tasks for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Left TLE
SRT LTS SRT CLTR SRT Delay WMS LM I WMS LM II BNT
41.95 31.59 6.05 91.86 88.51 48.25
N
M
SD
N
t
WMS VR I 100.44 16.91 63 99.80 18.10 75 0.22 WMS VR II 98.89 16.49 63 96.84 15.76 76 0.75 7=24 6.00 1.53 55 5.53 1.96 68 1.46 Immediate 7=24 Delay 5.56 1.51 62 5.47 1.80 75 0.34
p
d
.830 0.04 .457 0.06 .148 0.27 .734 0.05
WMS VR I ¼ Wechsler Memory Scale Visual Reproduction I subtest standard score; WMS VR II ¼ Wechsler Memory Scale Visual Reproduction II subtest standard score; 7=24 Immediate ¼ 7=24 Immediate Recall raw score; 7=24 Delay ¼ 7=24 Delayed Recall raw score.
classification accuracy of the Logical Memory I and II subtests. Prediction of left seizure focus based on the Logical Memory subtest resulted in a sensitivity of 56% and a specificity of 58%. Using a forward-stepwise logistic regression, we compared the predictive ability of SRT variables—LTS, CLTR, and Delay raw scores. The Hosmer and Lemeshow statistic was nonsignificant, X2(7) ¼ 1.92, p ¼ .96. The Delayed Recall trial of the SRT emerged as the only significant predictor of seizure laterality (Wald statistic ¼ 8.85, p ¼ .003). Presented in Table 5 is the classification accuracy of the SRT delay trial. Patients with an SRT delay score of 5 or less were classified as left TLE. Prediction of left seizure focus based on SRT delay raw scores resulted in a sensitivity of 60% and specificity of 65%. As in the first logistic regression, default SPSS settings and the enter method were used to evaluate the predictive ability of the BNT. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 11.11, p ¼ .20. The BNT was a significant predictor of the side TABLE 5 Logistic Regression Results for Prediction of Seizure Focus Predicted Seizure Focus
Right TLE Observed
M
SD
32
significant group differences on these variables. In the first logistic regression analysis, default Statistical Package for the Social Sciences (SPSS) settings and the enter method were used. In this analysis, the Logical Memory I and II subtest standard scores were entered as the predictor variable of the side of seizure onset. A forward regression was not used as previous t tests were not significant. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 7.24, p ¼ .51, which suggests that the chosen model adequately fit the data (significant values indicate lack of fit). However, the Logical Memory I and II subtests were not significant predictors of the side of seizure focus (Wald statistics for Logical Memory I ¼ 0.365, p ¼ .546; for Logical Memory II ¼ 2.306, p ¼ .129). Displayed in Table 5 is the
Variable
M
Right TLE
SD
N
M
SD
N
t
p
d
11.90 12.83 2.92 14.10 13.98 9.31
64 64 58 63 63 65
43.72 33.95 7.53 95.18 93.38 51.78
13.09 14.67 2.47 16.08 15.74 6.20
78 78 74 77 77 78
0.83 1.01 3.14 1.29 1.91 2.71
.406 .316 .002 .201 .058 .008
0.14 0.17 0.55 0.22 0.33 0.46
SRT LTS ¼ Selective Reminding Test Long-Term Storage raw score; SRT CLTR ¼ Selective Reminding Test Consistent Long-Term Memory Retrieval raw score; SRT Delay ¼ Selective Reminding Test Delayed Recall raw score; WMS LM ¼ Wechsler Memory Scale Logical Memory I and II subtest standard score; BNT ¼ Boston Naming Test raw score.
Left
Logical Memory I & II Left 18 Right 14 SRT Delay Left 28 Right 19 BNT Left 21 Right 16 SRT Delay and BNT Left 27 Right 18
Right
% Correct
45 63
28.6 81.8
30 55
48.3 74.3
44 62
32.3 79.5
31 56
46.6 75.7
SRT ¼ Selective Reminding Test; BNT ¼ Boston Naming Test.
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UMFLEET ET AL. TABLE 6 Logistic Regression Results for the SRT and BNT
Variable Step 1 SRT Delay raw Constant Step 2 SRT Delay raw BNT raw Constant
B
SE
p
exp b
0.20 1.14
0.07 0.49
.003 .022
1.23 0.32
0.18 0.05 3.57
0.07 0.03 1.29
.011 .036 .006
1.19 1.05 0.03
SRT ¼ Selective Reminding Test; BNT ¼ Boston Naming Test.
of seizure focus (Wald statistic ¼ 6.40, p ¼ .011). Displayed in Table 5 is the classification accuracy of the BNT. Patients with a BNT score of 46 or less were classified as left TLE. Prediction of left seizure focus based on the BNT resulted in a sensitivity of 57% and specificity of 59%. Lastly, we compared the predictive ability of the SRT delay and BNT variables in a forward-stepwise regression. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 7.57, p ¼ .48, again indicating good fit. Both the Delayed Recall trial of the SRT and the BNT emerged as significant predictors of side of seizure focus (Wald statistic for SRT ¼ 6.44, p ¼ .01; Wald statistic for the BNT ¼ 4.40, p ¼ .04). However, the BNT only minimally improved the model fit (improved Cox & Snell R2 by .03 and Nagelkerke R2 by .04) above and beyond the variability predicted by SRT Delayed Recall alone. Presented in Table 6 are results from the regression analysis. In Table 5, the classification accuracy of the SRT delay trial and BNT are displayed. Sensitivity and specificity results did not improve significantly with the combination of SRT delay and BNT (sensitivity ¼ 60%, specificity ¼ 64%). As predicted, regression analyses for Visual Reproduction I and II and 7=24 tasks were not significant. Sensitivity statistics of the visual memory tasks were lower than those for the verbal measures. Specifically, prediction of right seizure focus based on the Visual Reproduction I and II combination resulted in a sensitivity of 47% and specificity of 64%. Sensitivity and specificity of the 7=24 immediate and delayed combination were 42% and 32%, respectively.
DISCUSSION Our findings demonstrate differences in test sensitivities of verbal and nonverbal measures commonly administered to lateralize seizure focus in a TLE patient population. The current findings, combined with those of previous research (i.e., Loring et al., 2008), may be useful for informing clinicians in terms of their test selection
and use of cut scores. In the present investigation, we extended previous research by evaluating the sensitivity and specificity of the delayed recall components of two memory measures. We compared metrics within the SRT, a verbal list-learning test, and found that the SRT Delayed Recall was the only significant predictor of the side of seizure focus. Similar to the SRT Delayed Recall, the BNT raw score was a significant predictor of the side of seizure focus, whereas the Logical Memory subtest (I and II) did not yield significant findings. When the BNT and SRT delay tasks were combined, both tasks emerged as significant predictors of the side of seizure focus, though the BNT added minimal value to the overall model. The BNT was similar to the SRT delay in terms of sensitivity (57% for the BNT and 60% for the SRT) and was similar with respect to specificity (59% for the BNT and ¼ 65% for the SRT delay). Although the SRT and BNT were significant predictors, the findings were of modest magnitude in terms of sensitivity and specificity. As expected, the visual memory measures were not significant predictors of side of seizure focus and had the poorest sensitivity statistics. Similar to the findings of Loring et al. (2008), the BNT failed to notably add to the overall accuracy of the logistic regression model in terms of lateralizing seizure focus when included with a list recall task. The sensitivity of the BNT was similar to that reported by Loring et al. (2008; sensitivity ¼ 58%). The SRT Delayed Recall had better sensitivity for lateralizing seizure onset focus than did the Rey AVLT list-learning test as reported in Loring et al.’s (2008) study (sensitivity ¼ 48%). In contrast, Loring et al. (2008) found the CVLT learning trials to have the best sensitivity (69%), though the specificity was poor (39%). Comparisons between SRT Delayed Recall findings and delayed recall scores for the AVLT and CVLT were not possible as these data were not available in previous studies. The present findings suggest that the SRT Delayed Recall raw score, directly compared with the SRT learning trials, may be a better predictor of the side of seizure focus. Methodological strengths of this study include exclusion criteria based on Wada, EEG, and MRI results, which provides a cleaner sample of patients with right or left temporal-lobe dysfunction. Also, participants were administered all measures used in the data analyses and treated at the same center. Another strength of the study is that this is the first study to examine delayed recall from a list-learning task. Limitations of the present study include no direct comparisons with other list recall tasks such as the CVLT and AVLT or comparisons with non-TLE-focus patients. In addition, we used standard scores for the WMS subtests because different versions were administered over time as newer WMS manuals were published. In contrast, patients were administered the same versions of the
SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY
SRT and BNT. Furthermore, we only compared left to right TLE as there was an insufficient number of patients who were diagnosed with seizures arising from other brain regions such as the right or left frontal lobes. Our findings indicate that a list-learning task is better than a prose memory task for the measurement of verbal memory performance in a TLE population, which is consistent with what has been reported in the literature. These findings are consistent with studies showing correlations between list learning with SRT and hippocampal volume measures indicating that list learning is sensitive in this population with hippocampal pathology. While the WMS Logical Memory subtest is one of the most commonly used measures of verbal memory in presurgical and postsurgical epilepsy assessments and has face validity given the contextual nature of the material to be remembered, it is a relatively insensitive measure for lateralizing temporal seizure foci in a presurgical patient population (Lee et al., 2002). The lack of predictive ability of the Logical Memory subtest in terms of seizure laterality may be partly due to the design of the task. Specifically, the stories are not repeated across several learning trials, which may lead to variability in scores due to extraneous factors such as inattention, poor comprehension, anxiety, and differences in individual learning strategies. List-learning tasks with multiple learning trials and recall tasks allow individuals to improve with repeated exposure or provide evidence of a deficient learning curve rather than poor performance due to other previously mentioned reasons such as inattention (Jones-Gotman et al., 2010; Lee et al., 2002). Future research should focus on comparisons of sensitivity and specificity of commonly used list-learning and recall tests. The present study found that the Delayed Recall score of the SRT (cut score 5) was better than object naming (cut score 47) or other measures of verbal memory for predicting a left seizure focus when left TLE patients were compared with their right TLE counterparts. However, it is difficult to compare different list-learning tasks in the same population (e.g., AVLT, CVLT, SRT) because administering more than one list-learning task in a single session can cause proactive or retroactive interference. As previously stated, the primary purpose of the current investigation was to provide relevant psychometric findings to inform clinicians in terms of test selection and cut scores. We recognize that neuropsychological tests will not be used in isolation to determine seizure lateralization as would an EEG. However, neuropsychology tests complement these methods and seizure outcome is better in patients whose cognitive deficits lateralize to the side of the seizure focus (Helmstaedter, 2004). The best surgical candidate is one in whom multiple methods (e.g., EEG, MRI, Wada, positron emission tomography, neuropsychological testing) align
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with regard to the side of lateralized dysfunction. Also, prior research has shown that scores on preoperative neuropsychological testing are highly predictive of risk for postsurgical cognitive decline (e.g., Binder et al., 2008). Based on the aforementioned literature and our current findings, there is a consensus that verbal list-learning measures are critical in the preoperative work-up. List-learning and delayed recall scores have a modest ability to lateralize seizure-onset foci, are sensitive to decline with left ATL, and are used in regression formulae derived from fMRI and Wada testing for predicting outcome after left ATL (Binder et al., 2008). A consensus report regarding a neuropsychological test battery for the evaluation of patients with epilepsy (Loring et al., 2011) is available online via the National Institute of Health Common Data Elements Web site. Loring and coauthors (2011) recommend the AVLT as the measure of verbal learning and memory over other options (e.g., CVLT and SRT). We recognize that the SRT can be challenging to administer and score and that the standardization sample is small relative to other list-learning tasks. The SRT should still be considered an option for patients undergoing epilepsy surgery because it is available in the public domain and because currently, unlike the SRT, there is not functional imaging data from Rey AVLT relevant for predicting memory outcome after ATL. Finally, considering the inadequate predictive ability of the Logical Memory subtest, clinicians may wish to consider the Logical Memory subtest of the WMS-IV an optional measure. This recommendation aligns with the National Institute of Health Common Data Elements report, which notes that the different versions of the Logical Memory subtest have been variably associated with side of seizure focus. The current study supports the use of verbal list-learning measures in the preoperative work-up and is the first study to provide data on cut scores for the Delayed Recall trial of the SRT.
ACKNOWLEDGMENTS This study was a poster presentation at the Annual Meeting of the International Neuropsychological Society in Waikoloa, HI in February 2013.
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of temporal lobe origin: Convergent validation of memory constructs. Journal of Epilepsy, 1, 53–59. Loring, D. W., Lowenstein, D. H., Barbaro, N. M., Fureman, B. E., Odenkirchen, J., Jacobs, M. P., . . . Stout, A. (2011). Common data elements in epilepsy research: Development and implementation of the NINDS Epilepsy CDE Project. Epilepsia, 52, 1186–1191. Loring, D. W., Strauss, E., Hermann, B. P., Barr, W. B., Perrine, K., Trenerry, M. R., . . . Bowden, S. C. (2008). Differential neuropsychological test sensitivity to left temporal lobe epilepsy. Journal of the International Neuropsychological Society, 14, 394–400. Rao, S. M., Hammeke, T. A., McQuillen, M. P., Khatri, B. O., & Lloyd, D. (1984). Memory disturbance in chronic progressive multiple sclerosis. Archives of Neurology, 41, 625–631. Rausch, R., & Babb, T. L. (1993). Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. Archives of Neurology, 50, 812–817. Sabsevitz, D. S., Swanson, S. J., Hammeke, T. A., Spanaki, M. V., Possing, E. T., Morris, G. L., . . . Binder, J. R. (2003). Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery. Neurology, 60, 1788–1792. Sabsevitz, D. S., Swanson, S. J., Morris, G. L., Mueller, W. M., & Seidenberg, M. (2001). Memory outcome after left anterior temporal lobectomy patients with expected and reversed Wada memory asymmetry scores. Epilepsia, 42, 1408–1415. Saling, M. M., Berkovic, S. F., O’Shea, M. F., Kalnins, R. M., Darby, D. G., & Bladin, P. F. (1993). Lateralization of verbal memory and unilateral hippocampal sclerosis: Evidence of task-specific effects. Journal of Clinical and Experimental Neuropsychology, 15, 608–618. Sass, K. J., Buchanan, C. P., Kraemer, S., Westerveld, M., Kim, J. H., & Spencer, D. D. (1995). Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions. Neurology, 45, 2154–2158. Sass, K. J., Spencer, D. D., Kim, J. H., Westerveld, M., Novelly, R. A., & Lencz, T. (1990). Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology, 40, 1694–1697. Sherman, E. M., Wiebe, S., Fay-McClymont, T. B., Tellez-Zenteno, J., Metcalfe, A., Hernandez-Ronquillo, L. H., . . . Jette, N. (2011). Neuropsychological outcomes after epilepsy surgery: Systematic review and pooled estimates. Epilepsia, 52, 857–869. Swanson, S. J. (2006). Neuropsychological testing is of limited value for predicting the epileptogenic zone. In J. W. Miller & D. L. Silbergeld (Eds.), Controversies in epilepsy surgery (pp. 215–220). New York, NY: Marcel Dekker. Wechsler, D. (1987). Wechsler Memory Scale-Revised. San Antonio, TX: Psychological Corporation. Wechsler, D. (1997). Wechsler Memory Scale-Third Edition. San Antonio, TX: Psychological Corporation. Wechsler, D. (2009). Wechsler Memory Scale-Fourth Edition. San Antonio, TX: Pearson.
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Sensitivity and Specificity of Memory and Naming Tests for Identifying Left Temporal-Lobe Epilepsy Laura Glass Umfleet and Julie K. Janecek Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
Erin Quasney Department of Psychology, Marquette University, Milwaukee, Wisconsin
David S. Sabsevitz Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
Joseph J. Ryan Department of Psychological Science, University of Central Missouri, Warrensburg, Missouri
Jeffrey R. Binder and Sara J. Swanson Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.
Key words:
Boston Naming Test, logical memory, seizure, Selective Reminding Test, specificity, Wechsler Memory Scale
Neuropsychological testing is useful for predicting cognitive outcome following anterior temporal lobectomy (ATL; e.g., Binder et al., 2008) and for determining side Address correspondence to Laura Glass Umfleet, Department of Neurology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226. E-mail: lumfl[email protected]
of seizure focus (e.g., Loring, Hermann, Lee, Drane, & Meador, 2000; Loring et al., 2008). Although many studies have shown that neuropsychological testing is useful for predicting risk for naming and verbal memory decline after epilepsy surgery (e.g., Binder et al., 2008; Sabsevitz et al., 2003) and for detecting differences in cognitive performance between left and right ATL
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patients after surgery (e.g., Chelune, Naugle, Luders, Sedlak, & Awad, 1993; Lee, Yip, & Jones-Gotman, 2002; Sherman et al., 2011), there is more controversy about the usefulness of neuropsychological testing for determining the side of seizure focus (e.g., Akanuma et al., 2003; Loring et al., 2000; Rausch & Babb, 1993; Swanson, 2006). More specifically, while significant differences in verbal memory scores are found in patients following left and right ATL (left ATL patients perform more poorly than right ATL patients) and significant presurgical to postsurgical changes are found in patients following left ATL (e.g., Graydon, Nunn, Polkey, & Morris, 2001; Helmstaedter, Elger, Hufnagel, Zentner, & Schramm, 1996; Hermann, Connell, Barr, & Wyler, 1995), the finding of group differences between left and right ATL candidates preoperatively is less well supported (e.g., Akanuma et al., 2003; Helmstaedter et al., 1996; Rausch & Babb, 1993; Saling et al., 1993). Also, differences in nonverbal memory between left and right ATL patients as well as significant declines in nonverbal memory following right ATL are reported less reliably (e.g., Barr, 1997; Graydon et al., 2001; Hermann, Seidenberg, Schoenfeld, & Davies, 1997; Rausch & Babb, 1993). Mixed findings with respect to preoperative group differences between left and right temporal-lobe epilepsy (TLE) surgery candidates are likely due to multiple factors such as variability in measures used across studies, some of which may lack adequate psychometric characteristics (e.g., sensitivity) in a TLE population. The clinical utility of a test can be determined by examining group differences (e.g., right TLE vs. left TLE) in preoperative scores or by determining the sensitivity and specificity of the instrument. Time constraints limit the number of language and memory tests that can be conducted in a preoperative work-up, which underscores the importance of deriving sensitivity statistics for measures used. There are few studies that have reported sensitivity statistics for verbal tasks (Loring et al., 2000, 2008). For instance, Loring et al. (2008) found that the total recall across learning trials of the Rey Auditory Verbal Learning Test (AVLT; sensitivity ¼ 48%, specificity ¼ 67%) was superior in predicting seizure laterality compared with the California Verbal Learning Test (CVLT; sensitivity ¼ 69%, specificity ¼ 39%) and that the Boston Naming Test (BNT; sensitivity ¼ 58%, specificity ¼ 70%) was superior to the Multilingual Aphasia Examination Visual Naming task (sensitivity ¼ 75%, specificity ¼ 39%). Also, compared with the BNT, the AVLT emerged as the only significant predictor of side of seizure focus using logistic regression. Unfortunately, delayed recall trials of the AVLT and CVLT were not included in the analyses. Loring et al.’s (2000, 2008) research underscores the need for future studies to investigate the sensitivity and specificity of other verbal memory measures.
Research of this nature has been critical for the Common Data Elements Project commissioned by the National Institute of Neurological Disorders and Stroke. This project arose out of the need to standardize data collection across investigators, simplify data aggregation, facilitate development of evidence-based guidelines, and standardize disease characterization and outcome assessment (Loring et al., 2011). Although there are several studies that show support for the Selective Reminding Test (SRT; Buschke, 1973; Buschke & Fuld, 1974) with respect to measuring verbal memory dysfunction in TLE (e.g., Binder et al., 2008; Sabsevitz et al., 2001), there are no known investigations that specifically address its sensitivity and specificity in this population. Previous studies have focused on the relationship between the SRT and pathology variables as well as memory outcome following left ATL. For instance, evidence of a relationship between the SRT and neuroimaging in an epilepsy patient sample has been reported. Using a small sample of individuals who completed the SRT preoperatively, Sass et al. (1990) found a significant relationship between hippocampal pathology (i.e., cell density of CA3 and the hilus) and the Long-Term Retrieval score of the SRT in patients with left TLE. In a second study using a small sample with relatively less hippocampal neuron loss, Sass and coauthors (1995) showed a significant correlation between the cell density of the CA1 of the left hippocampus and the SRT in patients with left TLE. In terms of memory outcome following left ATL, greater declines have been observed with the SRT compared with the Logical Memory subtest (I and II) from the Wechsler Memory Scale (WMS; Wechsler, 1987, 1997, 2009). Also, Wada memory scores were associated with SRT outcome but not with Logical Memory outcome (Sabsevitz et al., 2001). In a study of the utility of functional magnetic resonance imaging (fMRI) language lateralization data for predicting verbal memory decline following left ATL, Binder and coauthors (2008) found that fMRI laterality indexes were stronger predictors of list-learning decline on the SRT than of declines in story memory on Logical Memory. Notably, patients in this study had scores that declined most on the Delayed Recall component of the SRT (55% of the group declined) followed by a smaller number of significant declines in SRT Long-Term Memory Storage (LTS; 45% of the group declined) and Consistent Long-Term Memory Retrieval (CLTR; 33% of the group declined) measures. In contrast to these studies that suggest that the SRT is a sensitive verbal memory measure for epilepsy surgery candidates, Loring, Lee, Martin, and Meador (1988) found minimal utility of the SRT for predicting side of seizure onset. However, these findings were based on a small sample of 16 patients with left TLE and 14 patients with right TLE.
SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY
Overall, previous studies have demonstrated that the SRT is sensitive to decline following left ATL, but studies have not addressed the test’s sensitivity and specificity for predicting the side of seizure focus. The SRT has several advantages including (like the AVLT) being available in the public domain, showing a robust decline after left ATL, and being one of the only tests on which decline can be predicted by preoperative fMRI (Binder et al., 2008). The present investigation examined the six-trial SRT (Buschke & Fuld, 1974), WMS Logical Memory subtest I and II (Wechsler, 1987, 1997, 2009), and the BNT (Kaplan, Goodglass, & Weintraub, 1983) to compare the sensitivity and specificity of these measures for determining side of seizure focus. In addition, the present study included the Delayed Recall trial of the SRT, which previously has not been reported. Although not a main focus of the present study, the WMS Visual Reproduction subtests I and II (Wechsler, 1987, 1997, 2009) and the 7=24 Spatial Recall Test (Rao, Hammeke, McQuillen, Khatri, & Lloyd, 1984) were examined to compare the sensitivity and specificity of these nonverbal memory measures to the side of seizure focus. Based on previous research, we hypothesized that the SRT would be a more sensitive measure of side of seizure focus than the Logical Memory subtest and BNT. Further, considering generally insignificant findings of prior studies, we expected that nonverbal memory measures would not be sensitive to lateralized dysfunction, though it is worthwhile to investigate to determine if group differences can be found using a larger number of participants. We also examined the predictive power of the aforementioned measures to show the contributions of these measures to the classification of side of seizure focus. The results of this study will inform future recommendations of test selection in neuropsychological evaluations of patients with epilepsy.
METHOD Participants Patients were retrospectively selected from series of 177 consecutive referrals with TLE and underwent standardized presurgical neuropsychological testing at the Comprehensive Epilepsy Program at the Medical College of Wisconsin from 1998 to 2013. All patients underwent long-term video electroencephalogram (EEG) monitoring, intracarotid sodium amobarbital (Wada) testing, and magnetic resonance imaging (MRI). Exclusion criteria included: (a) Wechsler Full-Scale IQ (FSIQ) < 70, (b) MRI showing contralateral neuropathology such as tumor, stroke, or mesial temporal sclerosis, (c) bilateral seizure foci based on
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EEG, and (d) Wada results indicating bilateral or right-hemisphere language dominance. This excluded 34 of the 177 patients. Participants included 143 patients, 65 with left TLE and 78 with right TLE. Most participants (90%) underwent anterior temporal-lobe resection (53 left TLE and 75 right TLE). The other 10% who did not undergo temporal-lobe resection had clear right or left temporal-lobe seizure focus based on EEG results. Engel Outcome Classifications (Engel, 1987) for individuals who underwent surgery were as follows: 88 Class I outcome (completely seizure-free), 15 Class II outcome (75% but .05). Effect sizes for these comparisons are also presented in Table 3. Although modest, the SRT Delayed Recall (ES ¼ .55) and BNT (ES ¼ .46) yielded the largest effect sizes. Included in Table 4 are results for group comparisons on visual memory measures. No significant group differences emerged on mean Visual Reproduction I and II and 7=24 Spatial Recall variables. Patient demographic information was not entered as covariates in regression analyses as there were no TABLE 1 Frequencies for Demographic Information for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Variable Sex Male Female Race Caucasian African American Other Handedness Right Left Mixed
Left TLE Frequency
Right TLE Frequency
30 35
38 40
61 2 2
70 6 2
58 5 1
61 9 7
Note. We speculate that there is a higher rate of left and mixed handedness in the right TLE group because a number of the lefthanded individuals with left TLE were removed from the study due to having right-hemisphere language dominance. This syndrome is known as pathological left handedness and occurs when disease or insult to the left hemisphere is associated with left handedness and reorganization of language to the right hemisphere.
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SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY TABLE 2 Demographic Means and Standard Deviations for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Left TLE Variable Age Education Seizure Frequency (# per month) Age at onset of Recurrent Seizures (years) Duration of Seizure Disorder (years) Total # of Seizure Medications Mesial Temporal Sclerosis Full-Scale IQ
TABLE 4 Means, Standard Deviations, and t Test Results for Visual Memory Tasks for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups
Right TLE
Left TLE
M
SD
N
M
SD
N
p
35.28 12.82 14.85
9.97 2.39 24.06
65 64 61
38.46 13.57 22.60
10.83 2.65 43.46
78 77 73
.07 .08 .22
16.62
11.37
64
17.55
11.60
78
.63
19.13
12.97
63
21.20
13.71
78
.36
2.00
0.73
65
1.96
0.81
78
.77
27 94.52
11.60
65
Variable
96.14
11.91
78
.42
TABLE 3 Means, Standard Deviations, and t Test Results for Verbal Memory and Confrontation Naming Tasks for Left Temporal-Lobe Epilepsy (TLE) and Right TLE Groups Left TLE
SRT LTS SRT CLTR SRT Delay WMS LM I WMS LM II BNT
41.95 31.59 6.05 91.86 88.51 48.25
N
M
SD
N
t
WMS VR I 100.44 16.91 63 99.80 18.10 75 0.22 WMS VR II 98.89 16.49 63 96.84 15.76 76 0.75 7=24 6.00 1.53 55 5.53 1.96 68 1.46 Immediate 7=24 Delay 5.56 1.51 62 5.47 1.80 75 0.34
p
d
.830 0.04 .457 0.06 .148 0.27 .734 0.05
WMS VR I ¼ Wechsler Memory Scale Visual Reproduction I subtest standard score; WMS VR II ¼ Wechsler Memory Scale Visual Reproduction II subtest standard score; 7=24 Immediate ¼ 7=24 Immediate Recall raw score; 7=24 Delay ¼ 7=24 Delayed Recall raw score.
classification accuracy of the Logical Memory I and II subtests. Prediction of left seizure focus based on the Logical Memory subtest resulted in a sensitivity of 56% and a specificity of 58%. Using a forward-stepwise logistic regression, we compared the predictive ability of SRT variables—LTS, CLTR, and Delay raw scores. The Hosmer and Lemeshow statistic was nonsignificant, X2(7) ¼ 1.92, p ¼ .96. The Delayed Recall trial of the SRT emerged as the only significant predictor of seizure laterality (Wald statistic ¼ 8.85, p ¼ .003). Presented in Table 5 is the classification accuracy of the SRT delay trial. Patients with an SRT delay score of 5 or less were classified as left TLE. Prediction of left seizure focus based on SRT delay raw scores resulted in a sensitivity of 60% and specificity of 65%. As in the first logistic regression, default SPSS settings and the enter method were used to evaluate the predictive ability of the BNT. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 11.11, p ¼ .20. The BNT was a significant predictor of the side TABLE 5 Logistic Regression Results for Prediction of Seizure Focus Predicted Seizure Focus
Right TLE Observed
M
SD
32
significant group differences on these variables. In the first logistic regression analysis, default Statistical Package for the Social Sciences (SPSS) settings and the enter method were used. In this analysis, the Logical Memory I and II subtest standard scores were entered as the predictor variable of the side of seizure onset. A forward regression was not used as previous t tests were not significant. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 7.24, p ¼ .51, which suggests that the chosen model adequately fit the data (significant values indicate lack of fit). However, the Logical Memory I and II subtests were not significant predictors of the side of seizure focus (Wald statistics for Logical Memory I ¼ 0.365, p ¼ .546; for Logical Memory II ¼ 2.306, p ¼ .129). Displayed in Table 5 is the
Variable
M
Right TLE
SD
N
M
SD
N
t
p
d
11.90 12.83 2.92 14.10 13.98 9.31
64 64 58 63 63 65
43.72 33.95 7.53 95.18 93.38 51.78
13.09 14.67 2.47 16.08 15.74 6.20
78 78 74 77 77 78
0.83 1.01 3.14 1.29 1.91 2.71
.406 .316 .002 .201 .058 .008
0.14 0.17 0.55 0.22 0.33 0.46
SRT LTS ¼ Selective Reminding Test Long-Term Storage raw score; SRT CLTR ¼ Selective Reminding Test Consistent Long-Term Memory Retrieval raw score; SRT Delay ¼ Selective Reminding Test Delayed Recall raw score; WMS LM ¼ Wechsler Memory Scale Logical Memory I and II subtest standard score; BNT ¼ Boston Naming Test raw score.
Left
Logical Memory I & II Left 18 Right 14 SRT Delay Left 28 Right 19 BNT Left 21 Right 16 SRT Delay and BNT Left 27 Right 18
Right
% Correct
45 63
28.6 81.8
30 55
48.3 74.3
44 62
32.3 79.5
31 56
46.6 75.7
SRT ¼ Selective Reminding Test; BNT ¼ Boston Naming Test.
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UMFLEET ET AL. TABLE 6 Logistic Regression Results for the SRT and BNT
Variable Step 1 SRT Delay raw Constant Step 2 SRT Delay raw BNT raw Constant
B
SE
p
exp b
0.20 1.14
0.07 0.49
.003 .022
1.23 0.32
0.18 0.05 3.57
0.07 0.03 1.29
.011 .036 .006
1.19 1.05 0.03
SRT ¼ Selective Reminding Test; BNT ¼ Boston Naming Test.
of seizure focus (Wald statistic ¼ 6.40, p ¼ .011). Displayed in Table 5 is the classification accuracy of the BNT. Patients with a BNT score of 46 or less were classified as left TLE. Prediction of left seizure focus based on the BNT resulted in a sensitivity of 57% and specificity of 59%. Lastly, we compared the predictive ability of the SRT delay and BNT variables in a forward-stepwise regression. The Hosmer and Lemeshow statistic was nonsignificant, X2(8) ¼ 7.57, p ¼ .48, again indicating good fit. Both the Delayed Recall trial of the SRT and the BNT emerged as significant predictors of side of seizure focus (Wald statistic for SRT ¼ 6.44, p ¼ .01; Wald statistic for the BNT ¼ 4.40, p ¼ .04). However, the BNT only minimally improved the model fit (improved Cox & Snell R2 by .03 and Nagelkerke R2 by .04) above and beyond the variability predicted by SRT Delayed Recall alone. Presented in Table 6 are results from the regression analysis. In Table 5, the classification accuracy of the SRT delay trial and BNT are displayed. Sensitivity and specificity results did not improve significantly with the combination of SRT delay and BNT (sensitivity ¼ 60%, specificity ¼ 64%). As predicted, regression analyses for Visual Reproduction I and II and 7=24 tasks were not significant. Sensitivity statistics of the visual memory tasks were lower than those for the verbal measures. Specifically, prediction of right seizure focus based on the Visual Reproduction I and II combination resulted in a sensitivity of 47% and specificity of 64%. Sensitivity and specificity of the 7=24 immediate and delayed combination were 42% and 32%, respectively.
DISCUSSION Our findings demonstrate differences in test sensitivities of verbal and nonverbal measures commonly administered to lateralize seizure focus in a TLE patient population. The current findings, combined with those of previous research (i.e., Loring et al., 2008), may be useful for informing clinicians in terms of their test selection
and use of cut scores. In the present investigation, we extended previous research by evaluating the sensitivity and specificity of the delayed recall components of two memory measures. We compared metrics within the SRT, a verbal list-learning test, and found that the SRT Delayed Recall was the only significant predictor of the side of seizure focus. Similar to the SRT Delayed Recall, the BNT raw score was a significant predictor of the side of seizure focus, whereas the Logical Memory subtest (I and II) did not yield significant findings. When the BNT and SRT delay tasks were combined, both tasks emerged as significant predictors of the side of seizure focus, though the BNT added minimal value to the overall model. The BNT was similar to the SRT delay in terms of sensitivity (57% for the BNT and 60% for the SRT) and was similar with respect to specificity (59% for the BNT and ¼ 65% for the SRT delay). Although the SRT and BNT were significant predictors, the findings were of modest magnitude in terms of sensitivity and specificity. As expected, the visual memory measures were not significant predictors of side of seizure focus and had the poorest sensitivity statistics. Similar to the findings of Loring et al. (2008), the BNT failed to notably add to the overall accuracy of the logistic regression model in terms of lateralizing seizure focus when included with a list recall task. The sensitivity of the BNT was similar to that reported by Loring et al. (2008; sensitivity ¼ 58%). The SRT Delayed Recall had better sensitivity for lateralizing seizure onset focus than did the Rey AVLT list-learning test as reported in Loring et al.’s (2008) study (sensitivity ¼ 48%). In contrast, Loring et al. (2008) found the CVLT learning trials to have the best sensitivity (69%), though the specificity was poor (39%). Comparisons between SRT Delayed Recall findings and delayed recall scores for the AVLT and CVLT were not possible as these data were not available in previous studies. The present findings suggest that the SRT Delayed Recall raw score, directly compared with the SRT learning trials, may be a better predictor of the side of seizure focus. Methodological strengths of this study include exclusion criteria based on Wada, EEG, and MRI results, which provides a cleaner sample of patients with right or left temporal-lobe dysfunction. Also, participants were administered all measures used in the data analyses and treated at the same center. Another strength of the study is that this is the first study to examine delayed recall from a list-learning task. Limitations of the present study include no direct comparisons with other list recall tasks such as the CVLT and AVLT or comparisons with non-TLE-focus patients. In addition, we used standard scores for the WMS subtests because different versions were administered over time as newer WMS manuals were published. In contrast, patients were administered the same versions of the
SENSITIVITY OF NEUROPSYCHOLOGICAL TESTS IN EPILEPSY
SRT and BNT. Furthermore, we only compared left to right TLE as there was an insufficient number of patients who were diagnosed with seizures arising from other brain regions such as the right or left frontal lobes. Our findings indicate that a list-learning task is better than a prose memory task for the measurement of verbal memory performance in a TLE population, which is consistent with what has been reported in the literature. These findings are consistent with studies showing correlations between list learning with SRT and hippocampal volume measures indicating that list learning is sensitive in this population with hippocampal pathology. While the WMS Logical Memory subtest is one of the most commonly used measures of verbal memory in presurgical and postsurgical epilepsy assessments and has face validity given the contextual nature of the material to be remembered, it is a relatively insensitive measure for lateralizing temporal seizure foci in a presurgical patient population (Lee et al., 2002). The lack of predictive ability of the Logical Memory subtest in terms of seizure laterality may be partly due to the design of the task. Specifically, the stories are not repeated across several learning trials, which may lead to variability in scores due to extraneous factors such as inattention, poor comprehension, anxiety, and differences in individual learning strategies. List-learning tasks with multiple learning trials and recall tasks allow individuals to improve with repeated exposure or provide evidence of a deficient learning curve rather than poor performance due to other previously mentioned reasons such as inattention (Jones-Gotman et al., 2010; Lee et al., 2002). Future research should focus on comparisons of sensitivity and specificity of commonly used list-learning and recall tests. The present study found that the Delayed Recall score of the SRT (cut score 5) was better than object naming (cut score 47) or other measures of verbal memory for predicting a left seizure focus when left TLE patients were compared with their right TLE counterparts. However, it is difficult to compare different list-learning tasks in the same population (e.g., AVLT, CVLT, SRT) because administering more than one list-learning task in a single session can cause proactive or retroactive interference. As previously stated, the primary purpose of the current investigation was to provide relevant psychometric findings to inform clinicians in terms of test selection and cut scores. We recognize that neuropsychological tests will not be used in isolation to determine seizure lateralization as would an EEG. However, neuropsychology tests complement these methods and seizure outcome is better in patients whose cognitive deficits lateralize to the side of the seizure focus (Helmstaedter, 2004). The best surgical candidate is one in whom multiple methods (e.g., EEG, MRI, Wada, positron emission tomography, neuropsychological testing) align
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with regard to the side of lateralized dysfunction. Also, prior research has shown that scores on preoperative neuropsychological testing are highly predictive of risk for postsurgical cognitive decline (e.g., Binder et al., 2008). Based on the aforementioned literature and our current findings, there is a consensus that verbal list-learning measures are critical in the preoperative work-up. List-learning and delayed recall scores have a modest ability to lateralize seizure-onset foci, are sensitive to decline with left ATL, and are used in regression formulae derived from fMRI and Wada testing for predicting outcome after left ATL (Binder et al., 2008). A consensus report regarding a neuropsychological test battery for the evaluation of patients with epilepsy (Loring et al., 2011) is available online via the National Institute of Health Common Data Elements Web site. Loring and coauthors (2011) recommend the AVLT as the measure of verbal learning and memory over other options (e.g., CVLT and SRT). We recognize that the SRT can be challenging to administer and score and that the standardization sample is small relative to other list-learning tasks. The SRT should still be considered an option for patients undergoing epilepsy surgery because it is available in the public domain and because currently, unlike the SRT, there is not functional imaging data from Rey AVLT relevant for predicting memory outcome after ATL. Finally, considering the inadequate predictive ability of the Logical Memory subtest, clinicians may wish to consider the Logical Memory subtest of the WMS-IV an optional measure. This recommendation aligns with the National Institute of Health Common Data Elements report, which notes that the different versions of the Logical Memory subtest have been variably associated with side of seizure focus. The current study supports the use of verbal list-learning measures in the preoperative work-up and is the first study to provide data on cut scores for the Delayed Recall trial of the SRT.
ACKNOWLEDGMENTS This study was a poster presentation at the Annual Meeting of the International Neuropsychological Society in Waikoloa, HI in February 2013.
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