Treatment outcome in patients with mesial temporal sclerosis.

The long-term prognosis of pharmacological therapy in patients with mesial temporal sclerosis (MTS) is generally considered poor. On the contrary, successful surgical therapy is frequently reported. We performed a retrospective case record survey of patients with MTS in a comprehensive epilepsy center between 1993 and 1999 in order to develop treatment strategies. The time period allowed access to high-resolution qualitative magnetic resonance imaging (MRI) and a minimum of 1-year outcome assessment. Eighty-three patients with intractable partial epilepsy with MRI and electroencephalograph (EEG) abnormalities and seizure semiology consistent with temporal lobe epilepsy were identified. Thirty-six patients were treated pharmacologically and surgically and 47 patients received only pharmacotherapy. The number of patients who became seizure free was in total 37 (45%); in the surgical group 26 and in the non-surgical group 11. The proportions of seizure-free patients in each group were 72% (surgical) and 23% (non-surgical). Clinical factors such as age, gender, lesion side, previous medical history, duration of illness, seizure frequency and IQ did not correlate to prognosis. A good seizure outcome was associated with early age of seizure onset, low number of previously used antiepileptic drugs (AEDs) and surgical treatment. There is a better long-term outcome in patients with MTS receiving surgical therapy in comparison with medical therapy.     

Type of preoperative aura may predict postsurgical outcome in patients with temporal lobe epilepsy and mesial temporal sclerosis

PurposeAs the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).MethodsIn this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or relapse. Outcome was compared between seven groups of patients according to their preoperative auras.ResultsTwo hundred thirty-seven patients were studied. The chance of becoming free of seizures after surgery in patients with abdominal aura was 65.1%, while in other patients, this was 43.3% (P = 0.01). In two-by-two comparisons, no other significant differences were observed.ConclusionPatients with medically refractory TLE–MTS who reported abdominal auras preceding their seizures fared better postoperatively with regard to seizure control compared with those who did not report auras, which may indicate bitemporal dysfunction, and to patients with other auras, which may indicate a widespread epileptogenic zone in the latter group of patients.     

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side‐of‐surgery and hemispheric dominance. First of all, patients showed material‐specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33–0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50–0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus – rather than a specific subfield pathology – is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. © 2014 Wiley Periodicals, Inc.     

Left mesial temporal sclerosis and verbal memory: a magnetoencephalography study.

The purpose of this study is to examine the pattern of mesial temporal lobe activity in patients with left mesial temporal sclerosis (LMTS) and normal control subjects during a verbal memory task using magnetoencephalography. Six LMTS patients and seven normal control subjects performed a word recognition task while event-related neuromagnetic responses were recorded for 248 trials in each of two runs. An equivalent current dipole model was used to localize activity sources and determine if the right or left mesial temporal lobe was active. All six (100%) LMTS patients but only two (28%) normal control subjects had right mesial temporal activity (P < 0.02). Two (33%) LMTS patients and 6 (86%) normal control subjects had left mesial temporal activity (P = 0.27). No significant differences in latency or duration of activity were seen between left and right sides or between groups. Our data suggest that patients with left hippocampal dysfunction are more likely to recruit the right mesial temporal lobe during verbal memory tasks than normal control subjects. A trend toward less left mesial temporal activity in LMTS patients is seen as well. Further study is needed to determine the predictive value of this technique regarding postresection memory outcome.     

Incipient preoperative reorganization processes of verbal memory functions in patients with left temporal lobe epilepsy

We previously reported nonlinear correlations between verbal episodic memory performance and BOLD signal in memory fMRI in healthy subjects. The purpose of the present study was to examine this observation in patients with left mesial temporal lobe epilepsy (mTLE) who often experience memory decline and need reliable prediction tools before epilepsy surgery with hippocampectomy. Fifteen patients with left mTLE (18–57 years, nine females) underwent a verbal memory fMRI paradigm. Correlations between BOLD activity and neuropsychological data were calculated for the i) hippocampus (HC) as well as ii) extrahippocampal mTL structures. Memory performance was systematically associated with activations within the right HC as well as with activations within the left extrahippocampal mTL regions (amygdala and parahippocampal gyrus). As hypothesized, the analyses revealed cubic relationships, with one peak in patients with marginal memory performance and another peak in patients with very good performance. The nonlinear correlations between memory performance and activations might reflect the compensatory recruitment of neural resources to maintain memory performance in patients with ongoing memory deterioration. The present data suggest an already incipient preoperative reorganization process of verbal memory in non-amnesic patients with left mTLE by simultaneously tapping the resources of the right HC and left extrahippocampal mTL regions. Thus, in the preoperative assessment, both neuropsychological performance and memory fMRI should be considered together.     

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.     

Episodic and semantic memory in children with mesial temporal sclerosis

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporal sclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive children and adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memory tests (short- and long-term memory and learning) and four semantic memory tests was compared with that of 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodic memory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, object naming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset, severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that children with MTS have episodic memory deficits and add new information on semantic memory. The data also demonstrate that clinical variables contribute differently to episodic and semantic memory performance.     

Prospective memory and mesial temporal epilepsy associated with hippocampal sclerosis

Episodic memory impairment is commonly observed in patients with epilepsy associated with mesial temporal sclerosis (MTS). Prospective memory (PM) is a set cognitive abilities that allow future performance of a present intention, in response to time- or event-based evocation cues, that trigger the intended action at the appropriate time. PM has not been evaluated in mesial temporal sclerosis. We evaluated the role of right and left hippocampal lesions on performance in both the retrospective and prospective PM components in patients with epilepsy secondary to mesial temporal sclerosis and correlated with performance in traditional neuropsychological tests, as well as with self-perception of memory impairment. We tested the hypotheses that a hippocampal lesion impacts on the prospective components of PM, and that a left-sided lesion had a greater impact on performance in the prospective component of PM than a right-sided lesion. We evaluated PM in 26 patients with right MTS, 22 left MTS patients, and 26 age-gender and education matched controls. The prospective component of PM was impaired in both patient groups, with both a lesion (patients performed significantly worse in the PM battery) and laterality effect (left MTS patients performed significantly worse than right MTS patients in the PM battery). Performance in the prospective component of the PM battery correlated with long-term delay performance in episodic verbal memory and self-perception of memory impairment in the left MTS group. The retrospective component was impaired in left MTS patients. Impaired performance was not accounted for solely by depression, anxiety or an antiepileptic drug effect. We conclude that mesial temporal lobe structures, including the hippocampus, play an important role in both the prospective and retrospective components of PM processes in tasks involving long delay intervals.     

Factors predicting seizure outcome of anterior temporal lobectomy for patients with mesial temporal sclerosis.

PURPOSE: To investigate the factors, including those associated with ictal scalp EEG results, related to surgical outcome in patients with pathologically proven mesial temporal sclerosis. METHODS: We studied 51 consecutive patients who underwent anterior temporal lobectomy and had at least 4 years of follow-up. Surgical outcome was classified as being seizure-free or not seizure-free during the first two and the subsequent two postoperative years. Clinical variables and scalp EEG parameters were subjected to statistical analysis. RESULTS: Of the 51 patients, 36 (70.6%) were seizure-free during postoperative years 3 and 4. Logistic regression analysis revealed that seizure remission for the first 2 years (p = 0.002) and contralateral propagated ictal discharges (p = 0.015) were independently related to seizure outcome at 4 years. Patients who were seizure-free at 2 years had an 86.5% chance of remaining seizure-free at 4 years. Of the patients without bitemporal asynchrony or switch of lateralization, 88.9% were seizure free at 4 years, compared with 54.5% of patients with asynchrony or switch of lateralization (p = 0.007). These two factors, however, were not predictive of seizure outcome at 2 years. CONCLUSIONS: Contralateral propagated ictal discharges, including bitemporal asynchrony and switch of lateralization, unfavorably influence long-term seizure outcome. Long-term seizure control is best when the patient has no such propagation patterns of ictal discharges and is seizure-free during the first 2 years after temporal lobectomy.     

Outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis without preoperative ictal recording

Purpose:   We report on the surgical outcome obtained in patients with refractory temporal lobe epilepsy with mesial temporal sclerosis (MTS) who were evaluated preoperatively without ictal recording and were submitted to corticoamygdalohippocampectomy.
Methods:   Two hundred twelve patients with refractory temporal lobe epilepsy were evaluated by means of clinical history, neurological examination, interictal electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological testing. MRI disclosed unilateral MTS in all patients. All patients were submitted to corticoamygdalohippocampectomy at the side determined by MRI.
Results:   Interictal EEG showed unilateral temporal lobe spiking in 176 patients; in 36 patients, bilateral discharges were found. Mean follow-up time was 2.7  years. One hundred ninety-four patients (92%) were classified as Engel's class I. Eighteen patients (8%) were rated as Engel's class II. Thirty-two out of 36  patients, in whom bilateral discharges were found, were in Engel's class I. Sixty percent of the patients had an improvement in memory function related to the nonoperated temporal lobe. Fifty-nine percent of the patients had a 10-point increase in general IQ postoperatively. Verbal memory decline was noted in three patients. Pathological examination showed MTS in all patients.
Conclusions:   It is possible to adequately select good surgical candidates for temporal lobe resection using MRI and interictal EEG alone. In patients with MRI-defined MTS, we should expect a 90% postoperative remission rate. Cognitive decline was very rarely seen in this patient population. The finding of MTS on MRI is the single most important prognostic factor for good outcome after temporal lobe surgery.     

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis

ObjectiveLittle is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance.MethodsResting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE = 22; right mTLE = 19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS.ResultsConnectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE.ConclusionOur results suggest that right hippocampal–left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal–frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS.     

Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engel's and ILAE classifications. The mean postoperative follow-up was 5.0 +/- 2.7 years. At the end of first year, 77.1% of patients were in Engel-I, and 52.7% were in ILAE-I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure-free for >or= 2 years that could be accepted as "cure." Thirty-six patients had recurrences, 19 had running-down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.     

Good surgical outcome in discordant ictal EEG-MRI unilateral mesial temporal sclerosis patients

Purpose: Video electroencephalography (vEEG) monitoring of patients with unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS. Contralateral seizure usually leads to an indication of invasive monitoring. Contralateral seizure onset on invasive monitoring may contraindicate surgery. We evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a consecutive series of uMTS patients with concordant and discordant vEEG findings, uniformly submitted to AMTL on the MRI evidence of MTS side without invasive monitoring.
Methods: We compared surgical outcome of all uMTS patients undergoing vEEG monitoring between January 1999 and April 2005 in our service. Discordant cases were defined by at least one seizure onset contralateral to the MRI evidence of MTS. Good surgical outcome was considered as Engel's class I. We also evaluated ictal SPECT concordance to ictal EEG and surgical outcome.
Results: Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%). Duration of follow-up was comparable in both groups: C = 56.1 ± 20.7 months versus D = 59.8 ± 21.2 months (p = 0.83, nonsignificant). Discordant single-photon emission computed tomography (SPECT) results did not influence surgical outcome.
Discussion: Surgical outcome was not influenced by contralateral vEEG seizure onset or contralateral increased flow on ictal SPECT. Although vEEG monitoring should still be performed in these patients, to rule out psychogenic seizures and extratemporal seizure onset, a potentially risky procedure such as invasive monitoring may not only not be indicated in this patient population, but may also lead to patients erroneously being denied surgery.     

Verbal memory disturbances in left temporal lobe epileptics

The relationship between laterality of paroxysmal discharges and characteristics of disturbances in memory functioning was investigated in temporal lobe epileptics. Subjects consisted of 22 temporal lobe epileptic patients, in whom the foci of the paroxysmal discharges were localized to one side of the temporal regions. The left focus group consisted of 10 patients; the right focus group, 12. Subjects were required to recognize verbal material presented to one hemisphere by means of a tachistoscope. The left focus group alone failed to demonstrate a right visual field superiority in these tasks. It was concluded that the left focus group specifically demonstrate disturbances in verbal memory functioning, particularly when stimuli were presented to the left hemisphere. Paroxysmal discharges seemed to interfere with normal memory functioning in the region where the foci of these discharges were found.     

Ictal singing due to left mesial temporal sclerosis.

Simple ictal or interictal automatisms are commonly seen in epilepsy, whereas complex automatisms are rare. Simple ictal vocalizations or appendicular automatisms have been reported to be due to mesial temporal lobe epilepsy. However, seizure-associated singing and dancing is very rare. We report a seventeen-year-old patient with ictal singing and rhythmic swinging of the arms as a dancing gesture. The video-EEG recording showed ictal left temporal lateralization and neuropathology confirmed left mesial temporal sclerosis.     

Rhinal cortex asymmetries in patients with mesial temporal sclerosis.

PURPOSE: The rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices, is one component of the limbic system that may be affected in patients with epilepsy and other temporal lobe pathologies. This study extended quantitative examination of the limbic system through development and validation of volumetric protocols to measure the ErC and PrC. METHODS: Volumes were calculated from MRI studies using ANALYZE 7.5 and based on detailed anatomical definitions developed for the study. Subjects were 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS: 33 left, 28 right) and 20 neurologically normal controls. Inter-rater reliabilities for the ErC and PrC volume protocols were found to be high (range 0.86-0.92). RESULTS: Ipsilateral hippocampal volume was reduced in patients with MTS, while contralateral volume did not differ significantly from controls. In the patients, rhinal cortex volumes were reduced as a function of laterality of disease. The pattern of correlations between ErC and PrC differed between disease groups. Hippocampal and rhinal cortex volumes were not significantly correlated. A significant four-way interaction was found between side of MTS, hemisphere, structure and handedness. CONCLUSIONS: This quantitative study demonstrates reliable in vivo evidence of morphometric changes in ErC and PrC in a substantial number of patients with unilateral MTS. The relationship observed between handedness, structure and disease status may suggest a role for cerebral dominance in modulating the expression of MTS.     

Emotional declarative memory assessment of patients with mesial temporal lobe epilepsy and patients submitted to mesial temporal lobectomy

Epileptic seizures generate cognitive and behavioral impacts in individuals who suffer from epilepsy. Declarative memory is one of the cognitive functions that can be affected by epileptic seizures. The main objective of this work was to investigate neurocognitive function, especially the emotional working memory of patients with unilateral mesial temporal lobe epilepsy, and that of patients submitted to unilateral mesial temporal lobectomy. A face recognition test that can simultaneously recruit the frontal lobe (working memory) and mesial temporal lobe (emotional memory) was used to investigate emotional working memory. Our findings showed that the epilepsy factor significantly compromised the performance in the emotional memory test. On the other hand, surgical removal of the epileptic focus promoted an improvement in the emotional working memory of these patients, in addition to the significantly decrease in the number of seizures.     

Safety of video-EEG monitoring and surgical outcome in patients with mesial temporal sclerosis and psychosis of epilepsy

PurposeCortico-amygdalohippocampectomy (CAH) has become an important treatment option for patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS); it has resulted in a 60–70% seizure remission rate and significant quality of life (QOL) improvements. Video-electroencephalography (VEEG) monitoring has been widely used in epilepsy centers for pre-surgical evaluation. A major concern in epilepsy surgery is whether to consider CAH treatment in patients with psychosis of epilepsy (POE). This study analyzed the safety and adverse events (AEs) of VEEG monitoring and the post-surgical outcomes of patients with refractory TLE-MTS and POE who underwent CAH.MethodClinical, sociodemographic and VEEG data from 18 patients with TLE-MTS and POE were analyzed. Psychiatric evaluations were performed using DSM-IV and ILAE criteria. The seizure outcome was evaluated using Engel's criteria.ResultsTwo patients (11.2%) presented AEs that did not result in increased lengths of hospitalization. Of the 10 patients (55.5%) who underwent CAH, 6 (60%) became free of disabling seizures (Engel I). The psychiatric and QOL evaluations revealed improvements of psychotic symptoms (p = 0.01) and in Physical Health (p = 0.01) following surgery.ConclusionThese data reinforce that VEEG monitoring is a safe method to evaluate patients with refractory TLE-MTS and POE in epilepsy centers.