Volumetric Magnetic Resonance Imaging Evidence of Bilateral Hippocampal Atrophy in Mesial Temporal Lobe Epilepsy

Summary: Purpose : We measured absolute volumes and volume differences of hippocampi in patients with mesial temporal lobe epilepsy (MTLE) using volumetric magnetic resonance imaging (MRI) to determine the extent of bilateral atrophy in MTLE and to relate hippocampal volumes (HV) to outcome of temporal lobectomy.
Methods : HV and hippocampal differences (HD) were measured in 40 patients with MTLE determined by pathology of hippocampal sclerosis (HS) and compared with those of age-matched controls. Results were matched with surgical outcome.
Results : Hippocampi contralateral to lobectomy (right hippocampi 2.96 ± 0.49 cm³, left 3.14 ± 0.51 cm³) were significantly smaller than those of controls (right hippocampi 3.73 ± 0.52 cm³, left 3.60 ± 0.51 cm³ but were significantly larger than hippocampi ipsilateral to lobectomy (right hippocampi 2.63 ± 0.61 cm³, 2.18 cm³) as compared across groups by analysis of variance (ANOVA: F = 27.2, p < 0. 0001). The smaller hippocampus was ipsilatera1 to lobectomy in 39 of 40 cases. Seven of 40 MTLE patients (18%) had bilateral atrophy, defined by volumes of each hippocampi 2 SD lower than control means. Surgical outcome was independent of hippocampal asymmetry and bilateral atrophy measured by chi-square and Fisher's exact tests.
Conclusions : We determined that most patients with MTLE have some degree of bilateral, asymmetric hippocampal pathology. However, asymmetry and bilateral atrophy have no clear relation to surgical outcome.     

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.     

Hippocampal deformation-based shape analysis in epilepsy and unilateral mesial temporal sclerosis

PURPOSE: To assess shape changes in patients with mesial temporal sclerosis (MTS) and temporal lobe epilepsy (TLE), by using deformation-based hippocampal shape analysis. METHODS: We retrospectively reviewed magnetic resonance imaging (MRI) studies in 30 subjects with unilateral MTS (15 right-sided MTS, 15 left-sided MTS) and TLE. We defined the "average" hippocampus in the right- and left-MTS groups by generating a mean transformation for the 15 deformation images in each group. Further to quantify the difference between the hippocampi, we coregistered the mean transformation of the involved hippocampus (with MTS) to the contralateral hippocampus, considering the left- and right-MTS groups independently. We generated a color "flame" scale showing degrees of outward and inward deviation of the coregistered hippocampi. RESULTS: Both the right- and left-MTS groups showed similar shape changes, with maximal inward deformation in the medial and lateral hippocampal head and the hippocampal tail. However, more extensive involvement was seen in the lateral hippocampal body in the right-MTS group as compared with the left. CONCLUSIONS: Deformation-based hippocampal shape analysis shows specific regions of hippocampal surface anatomy that are most affected in MTS. This technique may aid in detection of clinically significant anatomic abnormalities of the hippocampus in patients with epilepsy.     

Prognostic Value of Qualitative Magnetic Resonance Imaging Hippocampal Abnormalities in Patients Undergoing Temporal Lobectomy for Medically Refractory Seizures

Summary: In patients with temporal lobe epilepsy (TLE), high-resolution, magnetic resonance imaging (MRI) frequently demonstrates hippocampal atrophy and increased hippocampal signal. To assess the prognostic value of these findings, we studied 51 patients evaluated prospectively by a radiologist blinded to other preoperative evaluations. Thirty-one of 51 (61%) patients undergoing temporal lobectomy had visually apparent hippocampal atrophy o r increased hippocampal signal on MRI (25 ipsilateral 3 contralateral, and bilateral to the operated site). Patients with ipsilateral abnormalities became seizure-free more frequently than patients with normal scans [24 of 25 (96%) vs. 10 of 20 (50%) p < 0.015]. Both ipsilateral hippocampal atrophy and ipsilateral increased hippocampal signal independently predicted a seizure-free outcome. Qualitative MRI provides important prognostic information in patients undergoing temporal lobectomy.     

Bilateral Hippocampal Atrophy in Medial Temporal Lobe Epilepsy

Summary: Quantitative evidence of hippocampal atrophy has been correlated with site of seizure onset, hippocampal neuronal loss, and seizure relief after resection. Most studies have quantified hippocampal atrophy using ratios or differences between right and left hippocampal values. However, bilateral hippocampal atrophy may remain undetected by these techniques. To assess the frequency and implications of bilateral hippocampal atrophy, we studied absolute hippocampal volumes in 53 temporal lobectomy patients who had undergone intracranial electroencephalogram recordings preoperatively. Coronal images were constructed perpendicular to the longitudinal axis of the hippocampus. Atrophy was defined as >2 SD below control values in the volume of the posterior. 5 cm of the hippocampus. Five of 53 patients (9%)had bilateral hippocampal atrophy; four of these cases were undetected by ratios. Surgery was performed on the side of ictal onset in all five patients; four have been seizure-free for >2 years. These results suggest that (a) mesial temporal sclerosis can be present bilaterally and may go undetected by hippocampal ratio or difference measures; (b) ab-solute hippocampal volume values as well as ratios are needed to detect all patients with bilateral hippocampal atrophy; and (c) temporal lobectomy is not contraindicated in patients with bilateral hippocampal atrophy, but success depends on electroencephalographic documentation of the side of predominant ictal onset.     

Memory Performance in Older Adults Before and After Temporal Lobectomy for Pharmacoresistant Epilepsy

Little is known about the effects of epilepsy surgery on memory in older adults. The purpose of this study was to determine if older adults exhibit greater memory decline than younger adults after anterior temporal lobectomy (ATL). Patients 55 years and older at time of surgery (23 left, 14 right ATL, range 55–66 years) were compared to patients age 25–35 years (44 left, 33 right ATL) to assess differences in preoperative to postoperative change in WMS-III index scores. Repeated-measures ANOVAs and ANCOVAs revealed that older patients did not demonstrate greater decline than younger patients across any of the memory indices. Rather, in the left ATL group, older patients showed less decline than younger patients on the Auditory Delayed Memory Index. Similarly, in the right ATL group, older patients showed less decline than younger patients on the Visual Delayed Memory Index. These patterns were also apparent in frequency of individual change. Results provide preliminary evidence that older adults who are good candidates for ATL are not at greater risk for memory decline when measured at 7 months postoperatively.     

Functional Plasticity After Left Anterior Temporal Lobectomy: Reconstitution and Compensation of Verbal Memory Functions

Summary: Purpose: This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions. Methods: We evaluated preoperative and l-year-post- operative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe. resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test-retest data obtained in a group of 100 non-surgical patients with localization-related epilepsies (mean retest interval >12 months). Results: Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation. Conclusions: Our data indicate different time windows for the reconstitution and compensation of mesial and cortical as- pects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug-resistant localization-related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.     

Memory Complaints Before and After Temporal Lobectomy: Do They Predict Memory Performance or Lesion Laterality?

Summary: The relationships among self-report of memory, actual memory performance on objective tasks, and lesion laterality were examined in this longitudinal study. Right-handed adults (n = 47) with medically intractable seizures were assessed both preoperatively and 1 year after a left or right temporal lobectomy. Memory complaints remained stable or diminished postoperatively, whereas performance on material-specific memory tasks declined. Regression analyses showed that dosage of medications, seizure frequency and self-reported depression were predictive of postoperative memory complaints, although size of resection and age were not. Together, these data suggest that many patients have a positive though mistaken impression that their memory functions improved after temporal lobectomy, an impression influenced by their positive surgical outcomes. Memory complaints did not predict laterality of the lesion. Sex-laterality interactions were evident for both subjective and objective memory measures.     

Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy

Summary: Purpose : To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).
Methods : Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3–mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).
Results : As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.
Conclusions : Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Bilateral Hippocampal Volume Loss in Patients with a History of Encephalitis or Meningitis

Volumetric analysis of high-quality magnetic resonance imaging (MRI) scans identifies asymmetric hippocampal atrophy in most patients with temporal lobe epilepsy. However, bilateral hippocampal atrophy can be missed by unnormalized volume measures. We considered two patient groups with temporal lobe epilepsy, one with a history of febrile convulsions (FC, n = 14) and one with a history of encephalitis or meningitis (E/M, n = 12), to compare the prevalence of bilateral volume loss between the groups. A volume normalization process defines a normal range of hippocampal volumes in control subjects (n = 32). Normalized volumes indicated that 11 of 14 subjects with a history of FC had unilateral hippocampal atrophy and 9 of 12 subjects with a history of E/M had bilateral hippocampal atrophy as compared with the controls. Visual assessments of unilateral hippocampal atrophy (n = 17) correlated well with measured unilateral volume loss (n = 14), but visual assessment of bilateral hippocampal atrophy (n = 3) correlated poorly with measured bilateral volume loss (n = 12). Mean age at seizure onset was lower in the FC group (7 years) than in the E/M group (13 years), but other clinical features were similar between the two groups. Hippocampal volume normalization is necessary to detect bilateral volume loss, which is common in patients with a history of encephalitis or meningitis.     

The relationship between quantitative T2 relaxometry and memory in nonlesional temporal lobe epilepsy

PURPOSE: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. METHODS: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. RESULTS: In left temporal lobe-onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe-onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal-onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. CONCLUSIONS: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.     

Development of Hippocampal Atrophy: A Serial Magnetic Resonance Imaging Study in a Patient Who Developed Epilepsy After Generalized Status Epilepticus

Summary: Purpose : To investigate changes in hippocampal volume.
Methods : We used serial magnetic resonance imaging (MRI) in a patient who developed chronic epilepsy after having generalized tonic-clonic status epilepticus (SE). Five MRI investigations were performed during SE and a 58-month follow-up period. Hippocampal volumetric measurements and coregistration of scans were performed to detect hippocampal atrophy.
Results : During status both mesiotemporal regions returned a high signal on T,-weighted images. Two months after the onset of SE, bilateral hippocampal atrophy was detected. Further progressive hippocampal atrophy was detected in the subsequent 58 months by both hippocampal volumetric measurements and coregistration of scans.
Conclusions : Our findings suggest that hippocampal atrophy is a process that may continue after the end of the SE.     

前颞叶切除术对癫痫患者临床记忆商的影响

目的探讨前颞叶切除术前后癫痫患者临床记忆力的变化。方法58例颞叶癫痫患者均经前颞叶切除手术治疗,其中左侧手术者27例,右侧手术者31例。在手术治疗前后对其记忆商(MQ)进行测定,并比较分析手术预后、术前MQ与术后MQ的关系。结果51例预后EngleⅠ-Ⅱ级,其中术后MQ改善16例(31.4%),无变化30例,下降5例;7例预后Ⅲ-Ⅳ级,其中术后MQ无变化1例,下降6例;两组术后MQ改善率相差显著(P<0.01)。右侧手术者术后MQ评分均值显著高于术前(P<0.01),但左侧手术者手术前后MQ评分均值没有显著差异(P>0.05)。右侧手术组术后MQ改善率(35.5%,11/31)明显高于左侧手术组(18.5%,5/27)。术前MQ障碍者术后MQ改善率(38.5%,10/26)明显高于术前MQ优秀(0.0%,0/5)和中等者(22.2%,6/27)。结论经受了右侧前颞叶手术切除的癫痫病人术后MQ有明显改善,左侧手术者则无明显变化;颞叶癫痫患者的手术预后和术前MQ是影响其术后MQ变化的重要因素。     

Intracarotid Amobarbital Procedure as a Predictor of Material-Specific Memory Change After Anterior Temporal Lobectomy

Summary: Memory testing during the intracarotid amobarbital procedure (IAP) is used extensively to identify temporal lobe surgery candidates "at risk" for developing severe postoperative anterograde amnesia. However, the utility of the IAP in predicting commonly observed material-specific memory deficits has not been thoroughly investigated. We examined the utility of contralateral IAP memory testing, as an index of the functional capacity of the surgical temporal lobe, to predict postoperative material-specific memory changes on the Wechsler Memory Scale-Revised (WMS-R) in patients with left hemisphere speech dominance undergoing left (n = 32) and right (n = 31) temporal lobectomy (TL). Left TL patients who "passed" contralateral IAP memory testing (368% recognition of memory items) had significantly greater verbal memory decrements than those who "failed" the IAP, presumably as a result of removal of functional tissue. A similar relationship between contralateral IAP performance and visual memory performance was not observed among right TL patients. Thus, the functional adequacy of the tissue to be resected appears to be inversely related to postoperative verbal memory decrement, at least among left TL patients. This relationship is consistent with results of recent studies demonstrating an inverse relationship between verbal memory decrements after left TL and preoperative neuropsychological verbal memory performance, magnetic resonance imaging (MRI) hippocampal volumes, and degree of mesiotemporal sclerosis (MTS).     

Hippocampal Volumetry with Magnetic Resonance Imaging: A Cost-Effective Validated Solution

Summary: Purpose: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer-based method of volumetric data analysis. Methods: Using a 1.0–T scanner, we obtained 2–mmthick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20–38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743–50). Overlays of individual observers’ tracings were used to fine tune the selection of landmarks and boundaries. Filled-in silhouette pairs generated from these “training tracings” were compared to determine how well observers could visually quantify area differences. Results: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20–38 years, the mean right and left hippocampal volumes were 2,911 mm³ and 2,836 mm³, respectively. The lower limits of normal were 2,217 mm³ for the right and 2,178 mm³ for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10. Conclusions: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.     

Focal Cerebral Lesions Found by Magnetic Resonance Imaging in Cryptogenic Nonrefractory Temporal Lobe Epilepsy Patients

Brain magnetic resonance imaging (MRI) was studied in patients with mild-to-moderate temporal lobe epilepsy (TLE), well controlled by pharmacotherapy, and with normal computed tomographic (CT) scans. Magnetic resonance imaging abnormalities were found in 19 patients; of these, nine had abnormalities in temporomesial regions and four in temporobasal regions. Six patients had white matter MRI lesions of nonspecific significance. The temporomesial MRI lesions were compatible with sclerosis of Ammonis cornu. Patients with this MRI finding had more severe and longer lasting TLE than those without MRI abnormalities. The temporobasal lesions were interpreted as potentially developing brain lesions. Correlation between EEG and MRI findings was good. We conclude that MRI is more useful than CT for diagnosis of patients with mild-to-moderate TLE.     

Correlation of Hippocampal Neuronal Density and FDG-PET in Mesial Temporal Lobe Epilepsy

Summary: Purpose: Interictal [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60–80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE.
Methods: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA).
Results: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies.
Conclusions: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.     

Mesial Temporal Sclerosis: Pathogenesis, Diagnosis, and Management

Summary: Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity–alone or mixed with other pathologic features–for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure-free have tightly localized interictal abnormalities restricted to F7/F8, Spl/Sp2, T3/T4, and T5/T6 more than 96% of the time.
MRI abnormalities may be seen in 55% of patients with MTS if both "hard" and "soft" criteria are used or in 20% when only "hard" criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateral-izing and localizing preoperative information.     

颞叶癫患者的头颅磁共振显像异常表现分析

目的对颞叶癫(TLE)患者头颅磁共振成像(MRI)异常表现进行分析,为临床诊治TLE提供参考。方法对56例TLE患者的头颅MRI异常表现进行分析总结。结果 56例TLE患者头颅MRI主要表现为海马硬化、颞叶软化灶、颞叶肿瘤、颞叶皮质萎缩等。其中,颞叶肿瘤类型多样,主要为少突胶质瘤、星形细胞瘤、脑膜瘤。结论 TLE患者头颅MRI异常表现复杂多样,正确掌握其特点有助于TLE的诊治。