Postsurgical Memory Decline Research Articles

Preoperative white matter network organization and memory decline after epilepsy surgery.

Risk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE. One hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry). Higher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation). These preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

4 Preoperative International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) Phenotype is Associated with Postoperative Memory Decline Following Temporal Lobectomy

Objective:The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.Participants and Methods:347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.Results:The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.Conclusions:In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.

Clinical utility of Epitrack for differentiating profiles and patterns of post-surgical change in memory and quality of life in patients with drug-resistant epilepsy

Purpose To assess whether performance in attention and executive functions evaluated with the Epitrack screening tool before surgery can differentiate memory and quality of life (QOL) profiles, and detect different post-surgical change patterns in these variables in patients with epilepsy. Methods This is a longitudinal study. Seventy-seven patients with drug-resistant epilepsy (mean age = 37.91) underwent a neuropsychological assessment before and one year after surgery. Epitrack, a screening tool that exclusively evaluates attention and executive functioning, was administered in the pre-surgical assessment, and verbal and visual memory and QOL were assessed before and after surgery. Results Patients with impaired Epitrack performance had poorer verbal and visual memory than those with intact Epitrack performance, regardless of the time point (for all, p < 0.0001). They also showed a post-surgical decline in immediate verbal recall (p = 0.04) and discriminability (p = 0.001). Patients with intact Epitrack performance did not exhibit this decline. Epitrack total score significantly contributed to 13 and 11% of the variance of post-surgical changes in immediate verbal recall and discriminability, respectively. Epitrack groups did not differ in QOL profiles or changes, but post-surgical immediate verbal recall improvements were related to post-surgical QOL improvements. Conclusion Our findings underline the utility of Epitrack screening tool to detect different patterns of verbal and visual memory dysfunction, as well as to predict post-surgical verbal memory decline in patients with drug-resistant epilepsy. Patients with lower pre-surgical Epitrack scores appear to be at increased risk for post-surgical memory decline.

Drug load and memory during intracarotid amobarbital procedure in epilepsy.

Anti-seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear. To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment. Fifty-nine adult patients with drug-resistant epilepsy (mean age=36.1, SD=11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post-surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed. Total IAP memory score was associated with total ASM drug load (r=-0.30, p=0.02) and seizure frequency (r=-0.25, p=0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r=-0.33, p=0.04). The number of current ASMs was not related to IAP memory score (r=-0.16, p=0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p>0.07). Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies.

Memory outcomes of temporal lobe surgery in adults aged over 45years.

It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45years of age compared with younger patients. We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome. The presurgical MQ (median 88) in ≥45years age group was significantly lower than in both younger groups (median MQ=100 for ≤30years age group, p=0.002; median MQ=107 for 31-44years age group, p=0.002). Three years after the surgery, the MQ decreased significantly in ≤30years age group (p=0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome. Higher age at the time of surgery does not significantly increase the risk for postsurgical memory decline; however, older patients are more likely to have lowered presurgical MQ. We did not find significant differences in the impact of surgery on seizure outcome among the age groups. Epilepsy surgery appears to be a safe and effective method in the age over 45years even though an earlier surgery should be preferred.

Whole-brain functional correlates of memory formation in mesial temporal lobe epilepsy

The mesial temporal lobe is a key region for episodic memory. Accordingly, memory impairment is frequent in patients with mesial temporal lobe epilepsy. However, the functional relevance of potentially epilepsy-induced reorganisation for memory formation is still not entirely clear. Therefore, we investigated whole-brain functional correlates of verbal and non-verbal memory encoding and subsequent memory formation in 56 (25 right sided) mesial temporal lobe epilepsy patients and 21 controls. We applied an fMRI task of learning scenes, faces, and words followed by an out-of-scanner recognition test. During encoding of faces and scenes left and right mesial temporal lobe epilepsy patients had consistently reduced activation in the epileptogenic mesial temporal lobe compared with controls. Activation increases in patients were apparent in extra-temporal regions, partly associated with subsequent memory formation (left frontal regions and basal ganglia), and patients had less deactivation in regions often linked to the default mode and auditory networks. The more specific subsequent memory contrast indicated only marginal group differences. Correlating patients’ encoding activation with memory performance both within the paradigm and with independent clinical measures demonstrated predominantly increased contralateral mesio-temporal activation supporting intact memory performance. In left temporal lobe epilepsy patients, left frontal activation was also correlated with better verbal memory performance. Taken together, our findings hint towards minor extra-temporal plasticity in mesial temporal lobe epilepsy patients, which is in line with pre-surgical impairment and post-surgical memory decline in many patients. Further, data underscore the importance of particularly the contralateral mesial temporal lobe itself, to maintain intact memory performance.

Epilepsy surgery beyond 50 years: Long-term seizure and cognitive outcomes

IntroductionSurgery is a well-demonstrated effective treatment for patients with refractory epilepsy. However, there are scarce data about the efficacy in older patients. Endpoint was to evaluate the outcome of epilepsy surgery in pharmacorresistant patients operated in middle-late adulthood. MethodsWe conducted a retrospective observational study including patients who underwent a epilepsy surgery at age ≥ 50. Presurgical clinical data, type of surgery, and postsurgical seizure outcome and neurological complications, including neuropsychological assessment were analyzed. Minimum post-surgical follow-up was 1 year. ResultsWe identified 38 patients (22 males, 17 females) out of 350 patients who underwent a resective surgery with curative intention in our Epilepsy Unit (12%). Median age at surgery was 56 years (50–69), with median epilepsy duration of 42 years (4–67). Neuroimaging showed focal epileptogenic lesions in 37 patients, mainly mesial temporal sclerosis (21). Presurgical neuropsychological evaluation was available in 38 patients: 35 had deficits, mostly in verbal or visual memory.Twenty-eight patients underwent standard temporal lobectomy with amygdalohippocampectomy, 7 lesionectomy and 4 lobectomy. Median follow-up was 4.46 years (1–9.75). A good outcome was achieved by 86.8% (28 Engel I; 5 Engel II); 5 patients were studied with SEEG, without any complications. None had postsurgical permanent neurological complications. From 22 patients with available post-surgical neuropsychological assessment, 16 scored lower than in pre-surgical one, mainly in memory domain. ConclusionSurgical treatment of long-term refractory epilepsy in patients ≥50 years can be effective and safe. Post-surgical memory decline is a frequent side effect, but with a low impact in daily life.

B-28 Prognostic Utility of a Prediction Model for Memory Decline in Epilepsy Following Selective Amygdalohippocampectomy

Abstract Objective It is important to evaluate risk for post-surgical cognitive decline in a systematic and reliable fashion due to the variable risk of memory decline following epilepsy surgery. Mathematical risk models have been developed to predict post-surgical memory decline (e.g., Stroup et al., 2003), but few studies have evaluated their prognostic utility. This study evaluated the predictive value of the Stroup et al., (2003) multivariate risk factor model in predicting postoperative verbal memory outcome among epilepsy patients who underwent left selective amygdalohippocampectomy. Method This retrospective study included 16 left-sided localization-related epilepsy surgery patients who underwent neuropsychological evaluation pre- and post-surgery. Patients were assigned to two risk groups: mild to moderate risk (15 to 60%) and severe risk (&gt;61%) for postoperative memory decline, which was based on Stroup et al., (2003) criteria, suggesting that individuals with the highest risk had dominant hemisphere resections, no hippocampal sclerosis, normal Wada memory, and normal preoperative immediate and delayed memory scores. Memory decline was determined by pre- minus post-surgery memory test difference scores with 1.5 SD denoting a significant decline. Results The formula predicted postoperative memory decline with 75% accuracy for patients in the high risk group and no significant decline with 92% accuracy for patients in the mild to moderate risk group. Conclusion The results suggest that Stroup’s predictive formula for verbal memory outcome following epilepsy surgery may be useful for patients undergoing left selective amygdalohippocampectomy surgery, consistent with prior research suggesting prognostic utility with left temporal lobectomy patients (e.g., Johnson-Markve et al., 2009).

Electrical stimulation of the parahippocampal gyrus for prediction of posthippocampectomy verbal memory decline.

OBJECTIVE Epilepsy surgery is of known benefit for drug-resistant temporal lobe epilepsy (TLE); however, a certain number of patients suffer significant decline in verbal memory after hippocampectomy. To prevent this disabling complication, a reliable test for predicting postoperative memory decline is greatly desired. Therefore, the authors assessed the value of electrical stimulation of the parahippocampal gyrus (PHG) as a provocation test of verbal memory decline after hippocampectomy on the dominant side. METHODS Eleven right-handed, Japanese-speaking patients with medically intractable left TLE participated in the study. Before surgery, they underwent provocative testing via electrical stimulation of the left PHG during a verbal encoding task. Their pre- and posthippocampectomy memory function was evaluated according to the Wechsler Memory Scale-Revised (WMS-R) and/or Mini-Mental State Examination (MMSE) before and 6 months after surgery. The relationship between postsurgical memory decline and results of the provocative test was evaluated. RESULTS Left hippocampectomy was performed in 7 of the 11 patients. In 3 patients with a positive provocative recognition test, verbal memory function, as assessed by the WMS-R, decreased after hippocampectomy, whereas in 4 patients with a negative provocative recognition test, verbal memory function, as assessed by the WMS-R or MMSE, was preserved. CONCLUSIONS Results of the present study suggest that electrical stimulation of the PHG is a reliable provocative test to predict posthippocampectomy verbal memory decline.

Imaging memory and predicting postoperative memory decline in temporal lobe epilepsy: Insights from functional imaging

After medial temporal lobe epilepsy (MTLE) surgery, there is considerable individual variation in the extent, nature and direction of postoperative memory change. Before surgery, epileptic patients who are surgery candidates need precise information about the potential cognitive after effects, and particularly in temporal lobe epilepsy, postoperative memory changes. Clinical and neuropsychological data may bring useful information to predict the postoperative memory outcome, but, these data are not always sufficient to replace the Wada test, considered for a long time, as the gold standard to predict postoperative decline following surgery. In any case, numerous studies demonstrate that the Wada procedure can be nowadays reliably replaced by functional MRI (fMRI) activation studies. A vast majority of fMRI studies suggest that it is the functional adequacy of the resected hippocampus rather than the functional reserve of the contralateral hippocampus that determines the extent of postoperative memory decline. In addition, new functional neuroimaging procedures that explore more widespread network disruptions commonly found in MTLE such as diffusion-tensor imaging (DTI) or connectivity studies could in the future constitute a reliable approach combined with fMRI activation studies to significantly improve the prediction of postsurgical memory decline.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

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.

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.

Preictal versus ictal injection of radiotracer for SPECT study in partial epilepsy: SISCOM

A 27-year-old man had complex partial seizures and a dysembryoplastic neuroepithelial tumor (DNT) in the left inferior-basal temporal region. The patient's seizures consisted of incomprehensible speech, staring, unresponsiveness, fumbling and then looking around. For the brain SPECT study, radiotracer was injected during the preictal (11s prior to seizure onset), ictal (at 25 s out of 47 s seizure duration) and interictal periods. Interictal SPECT was subtracted from preictal or ictal-injection SPECTs and then the subtracted SPECTs were overlaid on the patient's MRI (SISCOM). SISCOM with preictal-injection SPECT showed hyperperfusion at the brain lesion, whereas SISCOM with ictal-injection SPECT showed hyperperfusion at the ipsilateral amygdala-hippocampus and hypoperfusion around the tumor lesion. After the DNT and nearby temporal lobe tissues were resected with preservation of amygdala-hippocampus, the patient became seizure free without complaint of subjective postsurgical memory decline. In this patient, SISCOM with preictal injection of radiotracer localized an epileptogenic zone, whereas SISCOM with the ictal injection showed hyperperfusion at the symptomatogenic zone.

Resection extent versus postoperative outcomes of seizure and memory in mesial temporal lobe epilepsy

To investigate the effects of the resection of hippocampus and temporal neocortex on postsurgical seizure and memory outcomes in mesial temporal lobe epilepsy (mTLE) patients. Sixty-eight mTLE patients underwent pre- and postsurgical brain magnetic resonance imaging (MRI). The patients were divided into seizure-free group (SF, N=54) and non-seizure-free group (NSF, N=14). The resection length of hippocampus was determined by the difference between presurgical and postsurgical hippocampus lengths in MRIs. The lengths of resected temporal gyri were measured on three-dimensional MRI reconstruction. Among SF group, 37 patients performed pre- and postsurgical neuropsychological tests. The postsurgical memory decline (PMD) was calculated by subtracting postsurgical memory score from presurgical one in verbal and visual memory tests. The resection length of hippocampus in SF was significantly longer than in NSF (32.7 +/- 7.7 mm versus 25.1 +/- 7.3 mm, t-test, p=0.002), regardless of intersubject difference in the extent of hippocampal sclerosis (logistic regression, p=0.003) while the resection lengths of the lateral temporal gyri were not different between SF and NSF. Overall postsurgical change of verbal or visual memory was not significant. However, regression analysis showed a significant correlation between the resection length of inferior or basal temporal gyrus and verbal PMD (p<0.001) in left TLE patients with seizure-free outcome. More resection of hippocampus may predict a better postsurgical seizure-free outcome. The larger resection of inferior or basal temporal gyrus seems to be related to a postsurgical verbal memory decline in left TLE patients.