Mesial temporal lobe epilepsy and hippocampal sclerosis: cognitive function assessment in Hispanic patients

PURPOSE: The goal of this study was to assess the cognitive function status in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (TLE+HS) to determine their cognitive function profile and to correlate material-specific memory deficits with HS laterality diagnosed by MRI. METHODS: Seventy-one patients were assessed with a neuropsychological protocol that includes IQ, attention, handedness, verbal memory, visual memory, language, and the executive function. chi(2) and correlation tests were used. RESULTS: Memory impairment was found in 46 patients (66%): patients without any memory deficit (n=25), patients with verbal memory deficit (n=21), patients with visual memory deficit (n=17), patients with deficit for both types of memory (n=8). Correlation between MRI lesion and memory was 66%. Language was impaired in 33 patients (46%). Eighteen patients (25%) had a deficit of the executive function. CONCLUSIONS: Patients with TLE+HS presented with a deficit in material-specific episodic memory correlating in large proportion with HS lateralization. We also found language and executive function impairments.     

Is the right amygdala involved in visuospatial memory? Evidence from MRI volumetric measures

Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.     

Correlation between 1H MRS and memory before and after surgery in mesial temporal lobe epilepsy with hippocampal sclerosis

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE-HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two patients underwent memory tests and 1H MRS investigation before and 6 months after SAH and were compared with nine control subjects. RESULTS: The 1H MRS scores were found to be significantly low on the pathological side of the patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of left TLE patients were correlated only with verbal memory scores. Statistical analysis did not reveal any significance for nonverbal memory scores for both TLE groups on either side, which showed no significant correlation between material specificity and 1H MRS findings. Conversely, regression analyses demonstrated that high right- and low left-sided 1H MRS values obtained before surgery may predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS can be considered as a useful tool to determine the lateralization in patients with MTLE-HS before the surgery. Although only a weak relation exists between the MRS values and memory scores, presurgical MRS scores may be predictive for a possible deterioration in verbal memory after surgery. However, further studies with higher numbers of cases are needed for confirmation of the results.     

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.     

Memory function during low intensity hippocampal electrical stimulation in patients with temporal lobe epilepsy

Hippocampal memory dysfunction is a main symptom of mesiotemporal lobe epilepsy (TLE). It may increase after temporal lobectomy for seizure relief. The aim of this study was to assess the ability of psychometry during hippocampal electrical stimulation to predict post-operative memory deficits and thereby to contribute to lateralization of the epileptogenic zone. A computerized memory test was performed during low intensity hippocampal stimulation in nine patients with TLE during invasive presurgical evaluation. The following results were obtained: speech dominant hippocampal stimulation induced subtle verbal memory deficits in patients with the epileptogenic zone in the speech dominant hemisphere and normal baseline memory performance. Verbal memory deficits could not be induced in patients with the epileptogenic zone in the speech dominant hemisphere and pre-existing memory deficits, or if the seizure origin was contralateral to speech dominance. Thus it was possible to lateralize the epileptogenic zone in patients with normal baseline memory performance by revealing hippocampal dysfunction only during electrical stimulation. Post-operative psychometric testing demonstrated that the individual risk for impairment of verbal memory performance following temporal lobectomy could be predicted correctly. In conclusion, psychometry during hippocampal stimulation may allow prediction of memory deficits following temporal lobectomy and improve determination of the epileptogenic zone.     

Correlation between calbindin expression in granule cells of the resected hippocampal dentate gyrus and verbal memory in temporal lobe epilepsy

Calbindin expression of granule cells of the dentate gyrus is decreased in temporal lobe epilepsy (TLE) regardless of its etiology. In this study, we examined the relation between reduction of calbindin immunoreactivity and the verbal and visuo-spatial memory function of patients with TLE of different etiologies. Significant linear correlation was shown between calbindin expression and short-term and long-term percent retention and retroactive interference in auditory verbal learning test (AVLT) of patients including those with hippocampal sclerosis. In addition, we found significant linear regression between calbindin expression and short-term and long-term percent retention of AVLT in patients whose epilepsy was caused by malformation of cortical development or tumor and when no hippocampal sclerosis and substantial neuronal loss were detected. Together with the role of calbindin in memory established in previous studies on calbindin knock-out mice, our results suggest that reduction of calbindin expression may contribute to memory impairments of patients with TLE, particularly, when neuronal loss is not significant.     

Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis

Purpose: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Methods: Forty‐five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist‐based recognition task following the Deese‐Roediger‐McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Results: Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. Discussion: HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.     

Hippocampal integrity and neurocognition in first-episode schizophrenia: A multidimensional study

Objectives. Impairments in memory and executive function are key components of schizophrenia. These disturbances have been linked to several subcortical and cortical networks. For example, anatomical and functional changes in the hippocampus have been linked to deficits in these cognitive domains. However, the association between hippocampal morphometry, neurochemistry and function is controversial. Therefore, we aimed to investigate the relationship between hippocampal anomalies and their functional relevance. Methods. Fifty-seven first-episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC) participated in this study. Hippocampal volumes were investigated using structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory was used as a hippocampus-dependent cognitive task whereas working memory and cognitive flexibility assessed frontal lobe function. Results. FE-SZ presented smaller volumes of the left hippocampus, with a significant correlation between left hippocampal volume and verbal memory performance (immediate recall). There was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr) and verbal memory (delayed recognition). Tests of cognitive flexibility and working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE-SZ demonstrated reduced performance in all of the assessed neurocognitive domains. Conclusions. These results point to a relationship between verbal memory and hippocampal integrity in schizophrenia patients which might be independent from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ might be linked specifically to hippocampal function.     

Material-specific lateralization of working memory in the medial temporal lobe

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.     

Neuropsychological performance and seizure-related risk factors in patients with temporal lobe epilepsy: a retrospective cross-sectional study

The aim of this study was to identify the neuropsychological features in patients with temporal lobe epilepsy (TLE) and their correlation with seizure-related variables. For this purpose, we carried out a retrospective analysis of data from 65 patients with TLE who had undergone a comprehensive neuropsychological assessment. The results suggest that the majority of patients with TLE were impaired in more than one cognitive domain, and among these patients, the mean proportions with defective semantic memory, language, motor/psychomotor speed, verbal episodic memory, and executive function were > 50% each. Moreover, age at seizure onset was the strongest predictor of general intellectual impairment, and number of antiepileptic drugs and seizure frequency could significantly predict deficits in verbal memory, language, and psychomotor speed. However, epilepsy duration was a less potent predictor of cognitive deficit than has been reported in cross-sectional studies.     

Neuropsychological performance and seizure-related risk factors in patients with temporal lobe epilepsy: A retrospective cross-sectional study

The aim of this study was to identify the neuropsychological features in patients with temporal lobe epilepsy (TLE) and their correlation with seizure-related variables. For this purpose, we carried out a retrospective analysis of data from 65 patients with TLE who had undergone a comprehensive neuropsychological assessment. The results suggest that the majority of patients with TLE were impaired in more than one cognitive domain, and among these patients, the mean proportions with defective semantic memory, language, motor/psychomotor speed, verbal episodic memory, and executive function were > 50% each. Moreover, age at seizure onset was the strongest predictor of general intellectual impairment, and number of antiepileptic drugs and seizure frequency could significantly predict deficits in verbal memory, language, and psychomotor speed. However, epilepsy duration was a less potent predictor of cognitive deficit than has been reported in cross-sectional studies.     

Semantic memory in partial epilepsy: verbal and non-verbal deficits and neuroanatomical relationships

Semantic memory was evaluated in 124 epilepsy patients, including 84 with left (n=44) or right temporal lobe epilepsy (TLE) (n=40) and 40 with left (n=25) or right frontal lobe epilepsy (FLE) (n=15), in order to determine their verbal and visual deficits, and the neuroanatomical relationships between them. The controls were 35 healthy subjects. Semantic memory was assessed by means of Picture Naming, Picture Pointing, the verbal Pyramid and Palm Trees Test (PPTT), the visual PPTT, Object Decision Hard, and Drawing From Memory. Episodic memory was assessed by means of the Short Story, Rey's Complex Figure, the Verbal and Visual Selective Reminding Procedure and Brown-Peterson Procedure. Factor analysis of the epilepsy patients distinguished their semantic memory scores from other neuropsychological domains. The semantic memory factor was significantly related to the side of the epileptic region, with lower scores in the left hemisphere and left TLE patients. In comparison with the controls, the left TLE patients were significantly impaired on Picture Naming, Picture Pointing, and Object Decision Hard. Subsequent analyses showed that, in comparison with the controls and the right TLE patients, the left TLE patients with lateral temporal lobe lesions were impaired in Picture Naming whereas, in comparison with the controls, the left TLE patients with mesial temporal lobe lesions were impaired in Object Decision Hard. On the contrary, the episodic memory factor was not related to the side of the epileptic region, and a few material-specific tests revealed opposite impairments in the left and right hemisphere patients. These results show that left TLE may cause semantic memory deficits involving verbal and visual information. Unlike the material-specific pattern of episodic memory, this pattern of impairment is in line with the view of an amodal semantic store in which all of the information about a thing overlaps. The semantic memory impairment may reflect damage in the lateral and mesial temporal lobe regions that impair neocortical functions in storing and retrieving information or hippocampal functions in processing meaningful stimuli.     

Long-term accelerated forgetting of verbal and non-verbal information in temporal lobe epilepsy

IntroductionWe investigated whether pre-surgical patients with temporal lobe epilepsy (TLE) forget verbal and non-verbal material faster than healthy controls over retention intervals of an hour and 6 weeks, and whether any observed memory loss was associated with structural changes to the hippocampus and/or seizure frequency.MethodsA mixed factorial design compared the performance of 27 patients with TLE and 22 healthy control participants, matched for IQ, age and gender, on tests of story recall and complex figure recall at three delays: immediate, 1 h and 6 weeks. Performance of the patient and control groups was matched at the immediate delay, which enabled comparisons of forgetting rate over the longer delays.ResultsWe found that TLE can affect the acquisition and retention of new memories over a relatively short delay of 1 h. This deficit was associated with structural hippocampal abnormality, with a material-specific effect that was particularly evident for the verbal task. We also found evidence of accelerated long-term forgetting in both patient groups, for the verbal and non-verbal tasks. It was demonstrated most strongly on the verbal task by the patients with right lateralized hippocampal sclerosis whose verbal recall was normal at the 1-h delay. Accelerated long-term forgetting was not associated with hippocampal pathology, but was associated with the frequency of epileptic seizures.DiscussionThe findings from the verbal task in particular provide evidence consistent with an extended period of memory consolidation that can be disrupted by both left and right TLE. The material-specific effects at the 1-h delay only, suggest that the initial consolidation of verbal and non-verbal, information depends on the integrity of the left and right hippocampus, respectively.     

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.     

Accelerated long-term forgetting in temporal lobe epilepsy: Verbal,nonverbal and autobiographical memory

Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performing within normal limits on standard memory tests. One possible explanation for this phenomenon is accelerated long-term forgetting (ALF). The present study investigated material‐specific ALF in patients with unilateral TLE and also examined whether ALF could be demonstrated on a novel, standardized anterograde autobiographical memory (ABM) task. Fourteen patients with TLE and 17 controls were administered verbal, nonverbal and ABM event memory tasks. The participants were tested for immediate recall, recall and recognition at 30‐minute delay, and recall and recognition after four weeks. The extent of ALF was calculated based on the percentage decay of memory from the 30‐minute delay trial to the four-week delay trial. Patients with left TLE showed significantly greater ALF for verbal material and a trend towards greater forgetting of ABM. Patients with right TLE showed a non-significant trend towards greater ALF for nonverbal material. Patients with unilateral hippocampal abnormalities showed greater ALF compared to patients without hippocampal abnormalities. Patients with seizures that generalize had more global memory deficits and greater ALF. We conclude that patients with unilateral TLE show material‐specific ALF, which appears to be more pronounced with an abnormal hippocampus or seizures that secondarily generalize.     

Learning and Memory Impairment in Patients with Temporal Lobe Epilepsy: Relation to the Presence, Type, and Location of Brain Lesion

PURPOSE: To study the influence of epileptogenic lesions on learning and memory alterations in patients with temporal lobe epilepsy (TLE). METHODS: We studied 131 patients (55 with left and 39 with right lesional TLE; 22 with left and 15 with right cryptogenic TLE) and 36 healthy subjects. We compared these groups by using a battery of tests to assess verbal and visual learning, delayed recall, and recall after the imposition of interfering activity. RESULTS: Compared with the controls and patients with right TLE, the patients with left TLE were significantly impaired on all verbal tests. On visual tests, patients with right TLE were impaired compared with controls but not more so than patients with left TLE. Separate multivariate analyses of variance (MA-NOVAs) of patients' verbal and visual test scores, taking the TLE side and morphologic features of the temporal lobes (i.e., normal, hippocampal sclerosis, low-grade glioma, or cavernous angioma) as independent factors, did not show any significant effect of these features. Separate comparisons of verbal and visual test scores of patients with lesional TLE, taking the side and location (mesial or lateral) of the epileptogenic lesion as independent factors, did not show any significant effect of location. CONCLUSIONS: Our findings show that some learning and memory abilities are impaired in patients with TLE irrespective of the presence of overt damage. This supports the theory that focal epileptic discharges, rather than the lesions themselves, affect these functions. The pathologic characteristics and intratemporal location of an associated lesion do not seem to play an important role in determining learning and memory impairment when clinical and treatment-related factors are taken into account.     

Hippocampal function and visual object processing in temporal lobe epilepsy

Limbic event-related potentials related to verbal but not to visual recognition memory have been found to be attenuated within the epileptic hippocampus of patients with temporal lobe epilepsy (TLE). To identify hippocampal contributions to visual processing and memory we recorded intracranial ERPs directly from within the epileptic and the non-epileptic hippocampus in 12 patients with unilateral TLE during a visual object decision and naming task. While the non-epileptic hippocampus differentiated reliably between real and nonsense objects, this effect was completely eliminated within the epileptic mesial temporal lobe. This finding suggests that the hippocampus proper contributes to the semantic processing of visual objects and may help to explain visual memory deficits in TLE.     

Number processing in temporal lobe epilepsy

BACKGROUND: Specific cognitive impairments have been found in association with mesial temporal lobe epilepsy (TLE), such as deficits in declarative memory or verbal abilities. No attention has been paid so far to possible deficits in number processing. OBJECTIVE: To investigate deficits in number processing in patients with TLE. METHODS: Numerical abilities were assessed in 28 right handed patients with medically intractable unilateral TLE and in a control group. RESULTS: No differences between patients and controls were found in analogue number processing with Arabic input, in a comparison task, or in simple addition and simple subtraction; however, there were significant group differences in tasks with verbal input, in simple division, in complex mental calculation, in a semantic knowledge task, and in conceptual tasks. Only minor differences were found between patients with right and left TLE. CONCLUSIONS: While numerical deficits may be expected in patients with left sided TLE, it is open for discussion why patients with right sided TLE also show numerical deficits.     

Preserved memory in temporal lobe epilepsy patients after surgery for low-grade tumour. A pilot study

The objective was to carry out a pilot study exploring memory outcome in patients with temporal lobe epilepsy (TLE) and low-grade tumour. A prospective study using a competence-related memory assessment was carried out in the Laboratory of Neuropsychology, Epilepsy Center and Neurosurgical Department of the “C. Besta” National Neurological Institute in 24 TLE patients undergoing surgical resection for left (n=12) or right (n=12) low-grade tumours and 36 healthy subjects. Patients underwent mesial or lateral temporal lobe lesionectomy. Neuropsychological tests exploring verbal and visual short-term memory, learning, delayed recall and ability to control interference in memory were applied. Before and after surgery, significant verbal impairment was present in left TLE patients compared to controls and right TLE patients, and visual deficits were present in both groups compared to controls. After surgery, there was no significant decrease in mean verbal or visual memory scores related to the operated side. Some memory abilities subserved by the contralateral temporal lobe improved. Postoperative memory scores were related to preoperative scores, side of operation, age and education. In patients with TLE and low-grade tumour, temporal lobe surgery does not necessarily induce memory deficits. Improvement of memory abilities subserved by the unoperated temporal lobe may be expected.     

Different structural correlates for verbal memory impairment in temporal lobe epilepsy with and without mesial temporal lobe sclerosis

Objectives: Memory impairment is one of the most prominent cognitive deficits in temporal lobe epilepsy (TLE). The overall goal of this study was to explore the contribution of cortical and hippocampal (subfield) damage to impairment of auditory immediate recall (AIMrecall), auditory delayed recall (ADMrecall), and auditory delayed recognition (ADMrecog) of the Wechsler Memory Scale III (WMS‐III) in TLE with (TLE–MTS) and without hippocampal sclerosis (TLE‐no). It was hypothesized that volume loss in different subfields determines memory impairment in TLE–MTS and temporal neocortical thinning in TLE‐no. Methods: T1 whole brain and T2‐weighted hippocampal magnetic resonance imaging and WMS‐III were acquired in 22 controls, 18 TLE–MTS, and 25 TLE‐no. Hippocampal subfields were determined on the T2 image. Free surfer was used to obtain cortical thickness averages of temporal, frontal, and parietal cortical regions of interest (ROI). MANOVA and stepwise regression analysis were used to identify hippocampal subfields and cortical ROI significantly contributing to AIMrecall, ADMrecall, and ADMrecog. Results: In TLE–MTS, AIMrecall was associated with cornu ammonis 3 (CA3) and dentate (CA3&DG) and pars opercularis, ADMrecall with CA1 and pars triangularis, and ADMrecog with CA1. In TLE‐no, AIMrecall was associated with CA3&DG and fusiform gyrus (FUSI), and ADMrecall and ADMrecog were associated with FUSI. Conclusion: The study provided the evidence for different structural correlates of the verbal memory impairment in TLE–MTS and TLE‐no. In TLE–MTS, the memory impairment was mainly associated by subfield‐specific hippocampal and inferior frontal cortical damage. In TLE‐no, the impairment was associated by mesial–temporal cortical and to a lesser degree hippocampal damage. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.