Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy

PURPOSE: Memory decline is often observed after anterior temporal lobectomy (ATL), particularly in patients with dominant hemisphere resections. However, the follow-up length has been 1 year or less in most studies. Our aims were to examine postoperative memory changes over a longer period and to identify baseline demographic and clinical predictors of memory outcome. METHODS: We administered material-specific memory tests at baseline, and 1 and 2 years after surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non-invasive presurgical protocol. Repeated measures multivariate analysis of variance (RM-MANOVA) was used to examine the relationship between changes in memory tests scores over time and side of TLE and pathology. Also, standardized residual change scores were calculated for each memory test and entered in multiple linear regression models aimed at identifying baseline predictors of better memory outcome. RESULTS: RM-MANOVA revealed a significant change in memory test scores over time, with an interaction between time and side of surgery, as 2 years after surgery patients with RTLE were improved while patients with LTLE were not worse as compared with baseline. Pathology was not associated with changes in memory scores. In multiple regression analysis, significant associations were found between right TLE and greater improvement in verbal memory, younger age and greater improvement in visuospatial memory, and male gender and greater improvement in both verbal and visuospatial memory. CONCLUSIONS: Our results suggest that the long-term memory outcome of TLE patients undergoing ATL without invasive presurgical assessment may be good in most cases not only for right-sided but also for left-sided resections.     

Subjective versus objective memory change after temporal lobe epilepsy surgery.

OBJECTIVE: To examine subjective versus objective memory change after anterior temporal lobectomy (ATL). METHODS: A prospective, controlled study. Controls included 39 unoperated patients with intractable temporal lobe epilepsy (TLE) who were administered a series of cognitive and health-related quality of life measures at baseline and at 12-month follow-up intervals. The surgery sample included 65 patients with intractable, focal TLE who had undergone either a right or left ATL. These patients were tested preoperatively and at 6-month follow-up intervals. Subjective and objective memory change was quantified using a newly developed methodology to control for practice effect and regression to the mean. RESULTS: Measures of subjective and objective memory change were not significantly related in the surgery sample. Prevalence of significant subjective memory decline 1 year after surgery ranged from 3 to 7%, whereas prevalence of significant objective memory decline ranged from 26 to 55%. Postoperative levels of emotional distress significantly predicted self-reported memory decline 1 year after ATL. Postoperative medication side effect and seizure outcome were also related significantly to subjective memory change in patients who had undergone left ATL. CONCLUSIONS: Subjective and objective memory change after temporal lobectomy are not related. Complaints of significant memory decline after ATL are infrequent and may serve as a marker for depression or other mood disorder rather than organically based memory decline.     

Preoperative FDG-PET temporal lobe hypometabolism and verbal memory after temporal lobectomy

OBJECTIVE: To examine the relationship of preoperative fluorodeoxyglucose (FDG)-PET asymmetry in temporal lobe metabolism and memory outcome after anterior temporal lobectomy (ATL). METHODS: In a university-based epilepsy surgery center, 60 ATL patients (27 left, 33 right) were divided into two groups: no/mild (n = 21) or moderate/ severe (n = 39) asymmetry in temporal lobe hypometabolism as determined by FDG-PET. All patients were nonretarded, at least 18 years of age, left-hemisphere speech dominant, without MRI abnormalities other than hippocampal atrophy, and with unilateral temporal lobe origin of intractable complex partial seizures. Neuropsychological measures of intelligence and verbal and visual memory function were assessed preoperatively and 6 months postoperatively. RESULTS: Left ATL patients with no/mild asymmetry in FDG-PET temporal lobe metabolism exhibited significantly greater verbal memory decline compared with left ATL patients with moderate/severe hypometabolism. There was no significant relationship between PET asymmetry and pre- to postsurgical IQ change. No significant relationship was observed between extent of PET hypometabolism and memory outcome for right ATL patients. CONCLUSIONS: FDG-PET asymmetry can be added to the preoperative clinical markers that appear useful in predicting verbal memory decline after left ATL.     

Intracarotid amobarbital procedure and prediction of postoperative memory in patients with left temporal lobe epilepsy and hippocampal sclerosis

PURPOSE: Although temporal lobe epilepsy (TLE) patients with dominant hemisphere hippocampal sclerosis generally have good cognitive outcome after anterior temporal lobectomy (ATL), a minority of patients experience at least mild post-ATL decline on one or more standardized measures of episodic and semantic memory. The goal of this investigation was to determine whether memory outcome in this group could be predicted from preoperative intracarotid amobarbital procedure (IAP) recognition memory scores. METHODS: Data from 22 left TLE patients were studied retrospectively. All were left hemisphere language dominant and had IAP scores for each hemisphere, a significant degree of pathology-confirmed left hippocampal sclerosis (HS+), and no positive MRI findings other than atrophy. Cognitive outcome status was represented by the number of pre- to post-ATL declines across three tests, as defined by 90th percentile Reliable Change Index (RCI) criteria. RESULTS: Only 14% of the sample exhibited decline on more than one memory test. Low right IAP (left hemisphere injection) scores and relatively high preoperative cognitive ability and age at surgery predicted a greater risk of post-ATL memory decline. CONCLUSIONS: A minority of left TLE HS+ patients experience at least a mild degree of RCI-defined decline in episodic or semantic memory after ATL. The right hemisphere IAP memory score, which reflects the functional reserve of the contralateral hemisphere, can help predict the risk of postoperative memory decline for TLE patients in whom HS+ is likely based on the presence of hippocampal atrophy on MRI or early age of seizure onset.     

Prediction of Verbal Memory Loss in Individuals After Anterior Temporal Lobectomy

Summary: Purpose : Decreased memory function represents the area of greatest neuropsychological morbidity after anterior temporal lobectomy (ATL), particularly for left ATL candidates. We wished to identify easily derived demographic and neuropsychological predictors of risk of pre-to postoperative memory decline using only information available preoperatively.
Methods : We assessed decline in memory as measured by the California Verbal Learning Test (CVLT) by deriving multiple regression equations using the following measures as independent variables: age at onset, chronological age at time of surgery, sex, Full Scale IQ (FSIQ), level of education, and preoperative memory scores. In all, 203 patients (93 males, 110 females), undergoing ATL (107 left, 96 right) with preoperative and 6-month postoperative testing, were examined.
Results : The combination of age, FSIQ, sex, side of surgery and preoperative score was highly predictive (p-values <0.0001) of postoperative memory scores. Higher postoperative scores were associated with higher preoperative score, younger chronological age, higher FSIQ, female sex, and right side of resection. Reliable change index (RCI) values were used to estimate meaningful decline on the total score across five trials. Logistic regression analysis showed preoperative score and age to be predictors of RCI decline for left-sided resections. Sensitivity of decline (≥90th centile RCI) prediction was 56%, and specificity was 95%. Validation in 30 patients from a separate population of patients undergoing left ATL produced similar figures.
Conclusions : The derived regression equations can accurately predict verbal memory decline on a list-learning task in-50% of individual patients undergoing ATL, and false-positive prediction errors are very rare.     

Individual Memory Change After Anterior Temporal Lobectomy: A Base Rate Analysis Using Regression-Based Outcome Methodology

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. Methods: Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. Results: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25–50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. Conclusions: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropscyhological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-to-the-mean before drawing predictive conclusions.     

Gender,Memory, and Hippocampal Volumes: Relationships in Temporal Lobe Epilepsy

Previous research has suggested bilateral hippocampal support for verbal memory in women with early left-hemisphere injury and that women experience better verbal memory outcome following anterior temporal lobectomy (ATL). The present study investigated two issues: (1) Do women have better verbal memory outcome following ATL compared with men? (2) Are verbal memory abilities differentially supported by the right and left hippocampus in males and females? Verbal memory performance [Wechsler Memory Scale: Logical Memory (LM) savings score] was assessed in 70 patients who underwent ATL. MRI volumetric measurements of the left and right hippocampus were performed. No LM savings score difference was found between groups preoperatively although a statistically significant gender effect (P < 0.04) was found for postoperative LM savings scores. Females displayed better postoperative memory performance, regardless of side of surgery. Preoperative verbal memory performance was not associated with right or left hippocampal volumes in either left or right ATL females, although the right hippocampus was positively associated with memory performance for left ATL males. Hippocampal volumes were not associated with postoperative LM savings scores for any group. Results suggest that prose recall was only modestly influenced by gender and that bilateral hippocampal support for prose recall was not present in our female patients.     

Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET

Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults: most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.     

Contents Index

Abstract

Visual recognition memory was examined in 310 normal adults (age range 18–91) and 60 patients with unilateral vascular lesions (30 right, 30 left) using the Continuous Visual Memory Test (CVMT). Significant age-related differences were found for both acquisition and delayed phases of the CVMT, with older subjects performing lower on all variables. Data from clinical groups revealed that both patients with left-hemisphere (LCVA) and right-hemisphere (RCVA) lesions performed below age-matched controls. However, RCVA patients performed significantly worse than LCVA patients. Data generally supported the double- dissociation hypothesis, with a majority of RCVA patients exhibiting impaired visual memory but preserved verbal memory, and vice versa for LCVA patients. Results also suggested that the CVMT Delayed task was less susceptible to potentially confounding effects of visual-spatial and verbal ability than was the acquisition phase.     

Predictors of postoperative memory function after left anterior temporal lobectomy

Patients who undergo left anterior temporal lobectomy (ATL) for intractable epilepsy are at risk of postoperative memory decline. This study attempts to identify the best predictors of memory after ATL using preoperative tests. Thirty-two consecutive patients who underwent left ATL with preoperative and postoperative neuropsychological testing were retrospectively identified. The following independent variables were analyzed by multiple regression: age of onset of seizures, age of temporal lobe damage, gender, MRI results, preoperative memory testing, and intracarotid amytal procedure (IAP) results. Neuropsychological measures of verbal and nonverbal memory served as dependent variables. Male gender (P<0.005), failing the IAP with both left and right hemispheres (P<0.001), and higher logical memory (LM) scores preoperatively (P<0.001) were associated with greater declines in LM after surgery. Our data demonstrate that the IAP predicts postoperative memory independent of other factors known to affect memory after left ATL.     

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.     

Relationship of Age at Onset, Chronologic Age, and Adequacy of Preoperative Performance to Verbal Memory Change After Anterior Temporal Lobectomy

Summary We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.     

Poor presurgical performance on both verbal and visual memory measures is associated with low risk for memory decline following left temporal lobectomy for intractable epilepsy

Studies have shown a lower risk for verbal memory decline following dominant anterior temporal lobectomy (ATL) among patients with poor, presurgical verbal memory scores. It is unclear however, if the risk of decline is increased in patients who also have reduced visual memory. Objective and subjective memory outcome following left ATL was examined in twelve patients with reduced presurgical visual and verbal memory scores. Only one patient demonstrated a meaningful decline in memory scores, with a decline in visual memory following surgery. Presurgically, this patient demonstrated poor memory bilaterally on Wada testing and small discrepancy in hippocampal volumes. She was also one of two patients who continued to have seizures post-surgery. This preliminary study suggests that patients with unilateral, left TLE and poor verbal and visual memory are unlikely to show meaningful memory declines following left ATL, particularly if they demonstrate expected patterns on Wada testing, hippocampal volume discrepancy (left < right), and postsurgical seizure-freedom.     

Effects of left temporal lobectomy and amygdalohippocampectomy on memory

This study examined the effects of left (dominant) temporal lobe surgery on verbal and visual memory in 38 patients with temporal lobe epilepsy. Twenty-five patients had anterior temporal lobectomy (ATL) and 13 had selective amygdalohippocampectomy (AH). All were administered the Rey Auditory Verbal Learning Test and a Complex Figure Test preoperatively and 1 year after surgery. ATL resulted in better seizure control overall. The ATL group as a whole showed a greater postoperative decline of their verbal memory than the AH group. A closer examination of the ATL patients showed there was a subgroup (n = 11) with better preoperative memory functioning that had the most significant decline. In contrast, only three patients in the AH group had better preoperative memory, and the majority (n = 10) matched the 'memory impaired' ATL patients. The changes in memory performance of the 'memory impaired' ATL and AH patients did not reach statistical significance. Postoperatively all patient groups improved in their verbal fluency.     

A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: Language lateralization versus hippocampal activation asymmetry

Purpose: Language lateralization measured by preoperative functional magnetic resonance imaging (fMRI) was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L‐ATL) resection. The aim of this study was to determine whether language lateralization or functional lateralization in the hippocampus is a better predictor of outcome in this setting. Methods: Thirty L‐ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre‐ and postoperative neuropsychological testing. A group of 37 right ATL (R‐ATL) surgery patients was included for comparison. Results: Verbal memory decline occurred in roughly half of the L‐ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome. Discussion: Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material‐specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes.     

Material-specific memory changes after anterior temporal lobectomy as predicted by the intracarotid amobarbital test

Summary: Purpose: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material‐specific aspects of IAT memory and material‐specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? Methods: Seventy left hemisphere language‐dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. Results: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. Conclusions: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.     

Visual recognition memory in normal adults and patients with unilateral vascular lesions

Visual recognition memory was examined in 310 normal adults (age range 18-91) and 60 patients with unilateral vascular lesions (30 right, 30 left) using the Continuous Visual Memory Test (CVMT). Significant age-related differences were found for both acquisition and delayed phases of the CVMT, with older subjects performing lower on all variables. Data from clinical groups revealed that both patients with left-hemisphere (LCVA) and right-hemisphere (RCVA) lesions performed below age-matched controls. However, RCVA patients performed significantly worse than LCVA patients. Data generally supported the double-dissociation hypothesis, with a majority of RCVA patients exhibiting impaired visual memory but preserved verbal memory, and vice versa for LCVA patients. Results also suggested that the CVMT Delayed task was less susceptible to potentially confounding effects of visual-spatial and verbal ability than was the acquisition phase.     

The effects of age on the learning and forgetting of primacy,middle, and recency components of a multi-trial word list

The serial position effect reveals that recall of a supraspan list of words follows a predictable pattern, whereby words at the beginning (primacy) and end (recency) of a list are recalled more easily than words in the middle. This effect has typically been studied using single list-learning trials, but in neuropsychology, multi-trial list-learning tests are more commonly used. The current study examined trends in learning for primacy, middle, and recency effects across multiple trials in younger and older age cohorts. Participants were 158 volunteers, including 79 adults aged 17–36 (“younger” group) and 79 adults aged 54–89 years (“older” group). Each participant completed four learning trials and one delayed (5–10 min) recall trial from the Memory Assessment Scales. Scores were divided into primacy (first four words), middle (middle four words), and recency (final four words) scores for all trials. For list acquisition, mixed effects modeling examined the main effects of and interactions between learning slope (logarithmic), age group, and serial position. Rate of learning increased logarithmically over four trials and varied by serial position, with growth of middle and recency word acquisition increasing more rapidly than recall of primacy words; this interaction did not differ by age group. Delayed retention differed according to age group and serial position; both older and younger adults demonstrated similar retention for primacy words, but older adults showed reduced retention for middle and recency words. Although older adults acquired less information across learning trials, the reason for this reduced acquisition was related to initial learning, not to rate of learning over time. Older compared to younger adults were less efficient at transferring middle and recency words from short-term to long-term memory.     

Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy

Transsylvian selective amygdalohippocampectomy (TSA) is an operative technique designed to spare unaffected brain tissue during surgical treatment for mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy (ATL), the advantages of TSA with respect to postoperative cognitive outcome are equivocal. We compared cognitive function before and after surgery in 49 patients with unilateral mesial temporal lobe seizures who underwent either ATL (n=17) or TSA (n=32). All patients received neuropsychological testing before and 1 year after surgery. The intelligence quotient (IQ) increased postoperatively in both surgical groups. Memory evaluation in the ATL group revealed a postoperative decline in nonverbal memory after right-sided resection and a postoperative decline in verbal memory after left-sided resection. In the TSA group, there was a slight postoperative decline only in verbal memory after left-sided resection, but other memory function was well preserved. In particular, there was significant postoperative improvement in verbal memory after right-sided resection. Overall, memory function was better preserved in the TSA group than in the ATL group.     

Effects of temporal lobe epilepsy on retrograde memory

PURPOSE: In a previous investigation (Lah et al., 2004), we found deficits in retrograde memory in patients who had undergone temporal lobectomy (TL). In this study, we set out to determine whether such deficits are present before surgery in patients with temporal lobe epilepsy (TLE). METHODS: Memory for public and autobiographic facts and events was assessed in patients with focal left-sided (n=15) or right-sided (n=14) TLE and healthy control subjects (n=15). The impact of epilepsy and underlying cognitive deficits on retrograde memory also was examined. RESULTS: Patients with left TLE demonstrated retrograde memory deficits across domains. Patients with right TLE showed defective recall only in the autobiographic domain. Young age at onset (younger than 14 years) was associated with greater difficulties in recall of famous events, and patients receiving polytherapy had significantly reduced recall of autobiographic events compared with those receiving monotherapy. In most cases, deficient memory for the past was associated with impairments in other cognitive skills, especially language abilities. CONCLUSIONS: In unoperated-on patients with TLE, we found deficits in retrograde memory that were similar to those seen after TL, with the pattern of deficits being influenced by side of lesion, anticonvulsant medication, and word-finding deficits. Unlike patients tested after right TL, patients with right TLE did not have difficulty recalling details of famous events, which raises the possibility that right TL results in a decline in this aspect of retrograde memory.