Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.     

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is characterized by its well‐defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult‐onset MTLE‐HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE‐HS. A case‐control study was carried out with 100 patients with MTLE‐HS and 50 healthy controls. Sera samples from subjects were tested by indirect immunofluorescence assay for detection of anti‐N‐methyl‐d ‐aspartate receptor (NMDA‐R), anti‐contactin‐associated protein‐like 2 (CASPR2), anti‐leucine‐rich glioma inactivated 1 (LGI1), anti‐gamma aminobutyric acid B receptor (GABA‐B‐R), anti‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid 1 and 2 receptors (AMPA‐1‐R and AMPA‐2‐R), and enzyme‐linked immunosorbent assay for detection of anti‐glutamic acid decarboxylase 65 (GAD65). Mean age of patients and controls was 41.2 vs 42 years, and 55% vs 56% were female. Mean duration of epilepsy was 27.2 years. No neuronal autoantibodies were found in either group, except for anti‐GAD65 in 3 patients and 2 controls. This study adds to the mounting evidence that, in Brazilian patients, MTLE‐HS without signs and symptoms of autoimmune encephalitis may be infrequently associated with these autoantibodies. Differences regarding accuracy of used methodologies for autoantibody detection and genetic and environmental characteristics are discussed. Further works with different methodologies tested simultaneously in different populations may help clarify the incongruent study results about autoantibodies in MTLE‐HS.     

ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis

Experts discussed the definition, natural history, pathologic features, pathogenesis, electroclinical, neurophysiological, neuropsychological, structural and functional imaging findings, as well as surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting consensus process the ILAE Commission Neurosurgery of epilepsy accepted the resulting conclusions as state-of-the art report on MTLE-HS. The majority of contributors considered MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity.     

Correlation study of optimized voxel-based morphometry and (1)H MRS in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Purpose:

To assess whether structural and metabolic brain abnormalities are correlated in MTLE/HS syndrome.

Methods:

Optimized voxel‐based morphometry (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton magnetic resonance spectroscopy measurements from both‐sided hippocampal and thalamic regions were performed in 20 MTLE/HS patients and 20 sex‐ and age‐matched healthy controls. The local GMC and GMV values were calculated in both the affected and unaffected hippocampi and ipsilateral and contralateral thalami in patients and healthy subjects, and these were compared. VBM variables and NAA, NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were correlated.

Results:

(1) Analysis revealed significantly more extensive GMV reduction than GMC reduction in patients' affected hippocampus. In addition, significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS patients. (2) Significant decreases in all VBM and MRS variables were revealed in the affected hippocampus. Whilst practically normal GMC values were revealed in patients' both‐sided thalamic regions, a significant decrease in local GMV and metabolic measurements were found in the patients' ipsilateral thalamus. (3) Pearson's correlations between structural and metabolic abnormalities were significant for the ipsilateral thalamus only.

Conclusion:

Structural and metabolic abnormalities as detected by optimized voxel‐based morphometry and ¹H MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS patients. It seems therefore reasonable that both methods reflect different aspects of brain pathology, which, at least to some degree, might be independently ongoing. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

     

磁共振表现为一侧海马硬化的颞叶癫痫手术治疗长期随访结果

目的：探讨磁共振表现为一侧海马硬化的颞叶癫痫手术治疗长期疗效。方法对25例磁共振表现为一侧海马硬化的药物难治性颞叶癫痫患者,在术中脑电监测下行裁剪式前颞叶切除术,术后长期随访,评估癫痫控制效果。结果术后疗效良好,癫痫控制效果按ILAE分类法,术后1年76％患者达1级,4％为2级,16％为3级,4％为5级;术后3年68％为1级,4％为2级,24％为3级,4％为5级;术后5年65％为1级,29％为3级,6％为5级。结论手术治疗磁共振表现为一侧海马硬化颞叶癫痫长期疗效满意,患者生活质量改善。     

Postoperative seizure and memory outcome of temporal lobe epilepsy with hippocampal sclerosis: A systematic review

We conducted a systematic review and meta-analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis (HS) subtypes classified by International League Against Epilepsy (ILAE) Consensus Guidelines in 2013. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2013 to August 6, 2023. Observational studies reporting seizure and memory outcomes among different HS subtypes were included. We used the Newcastle–Ottawa scale to assess the risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the quality of evidence. Seizure freedom and improved outcome (Engel 1 or ILAE class 1–2) ≥1 year after surgery were defined as the primary and secondary seizure outcome. A random-effects meta-analysis by DerSimonian and Laird method was performed to obtain pooled risk ratio (RRs) with 95% confidence interval (CIs). The memory impairment was narratively reviewed because of various evaluation tools. Fifteen cohort studies with 2485 patients were eligible for the meta-analysis of seizure outcome. Six cohorts with detailed information on postoperative memory outcome were included. The pooled RRs of seizure freedom, with moderate to substantial heterogeneity, were .98 (95% CI = .84–1.15) between HS type 2 and type 1, 1.11 (95% CI = .82–1.52) between type 3 and type 1, and .80 (95% CI = .62–1.03) between the no-HS and HS groups. No significant difference of improved outcome was found between different subtypes (p > .05). The quality of evidence was deemed to be low to very low according to GRADE. The long-term seizure outcome (≥5 years after surgery) and memory impairment remained controversial.     

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry

OBJECTIVE: Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. MATERIAL AND METHODS: Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. RESULTS: Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). CONCLUSION: Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome.     

海马MRI提示为海马硬化的颞叶癫痫患者的术后随访

目的观察磁共振上提示有海马硬化的颞叶癫痫患者的手术疗效。方法术后电话及定期复查脑电图对磁共振提示为海马硬化且经病理证实为海马硬化的患者进行随访,至少随访两年的患者纳入实验,随访结果采用统计软件SPSS 17.0进行统计分析,定性资料的比较,选择卡方检验,以P<0.05为有统计学意义,分析术后癫痫控制的情况。结果对于有海马硬化的患者,与发作间期异常放电一致均有满意的手术效果;对于影像学上有明显海马硬化的患者术后6年内随访发现癫痫有效率分别为90.66%,88.57%,88.25%,86.20%,72%,69.04%,差异有统计学意义。结论手术是治疗伴有海马硬化的颞叶癫痫的有效方法,一旦影像学上提示海马硬化,且脑电图监测能够定侧的颞叶癫痫,应该及早手术。     

Memory in patients with drug-responsive mesial temporal lobe epilepsy and hippocampal sclerosis

PURPOSE: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is the most common of the antiepileptic drug (AED)-resistant seizure syndromes that are remediable mostly with surgery, although a small group of patients have benign prognosis with fewer seizures. Material-specific memory impairment is an important feature in these patients and may be related to both the structural abnormality and the frequent seizures. In this study, we investigated the relation between memory deficit and HS by taking seizure frequency into account. METHODS: The patients were evaluated according to a standard protocol and divided into two groups, considering their response to AEDs: the good-responder group (GRg, n = 18) and the pharmacoresistant group (PRg, n = 95). They were administered a neuropsychological test battery that included verbal and nonverbal memory tests, compared with each other and with a normal control group (n = 29). The responder group was evaluated by the same battery once again (mean, 23 months; SD, 8.25; range, 14-38 months). RESULTS: Both GR and PR patient groups had poorer memory than the normal controls in all memory tests (p < 0.05). However, the comparison of GRg with PRg revealed that only the digit-span test was significantly worse in PRg (p = 0.0061), and no difference was found in any other memory scores. The reevaluation of the GRg showed no significant difference between the first and second evaluation. CONCLUSIONS: We concluded that the memory impairment in patients with MTLE-HS was permanent and might be related to the direct effect of HS itself. Therefore patients with good response to AEDs can be used as a model for investigating the memory problems in patients with MTLE-HS.     

Review: Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: Clinical,pathological and neuroimaging evidence

Cognitive decline is increasingly described as a co‐morbidity of temporal lobe epilepsy (TLE). Mechanisms underlying cognitive impairment are not fully understood despite examining clinical factors, such as seizure frequency, and cellular mechanisms of excitotoxicity. We review the neuropsychometry evidence for progressive cognitive decline and examine the pathology and neuroimaging evidence supporting a neurodegenerative process in hippocampal sclerosis (HS)‐related TLE. Accelerated cognitive decline is described in groups of adult HS‐related TLE patients. Large childhood studies show early onset of seizures result in poor development of verbal memory and a hindrance in achieving cognitive potential. We discuss HS classification according to different patterns of neuronal loss and correlation to post‐temporal lobectomy cognitive outcomes in refractory TLE patients. Factors such as lateralization of HS pathology, neuronal density and subtype have correlated to cognitive outcomes with varying significance between different studies. Furthermore, alterations in neuronal maturity, regenerative capacity and aberrant connectivity appear to affect cognitive performance post‐operatively suggesting a complex multifactorial process. More recent studies have identified tau pathology being present in HS‐related TLE and correlated to post‐operative cognitive decline in some patients. A traumatic head injury‐related or novel tauopathy has been hypothesized as an underlying process. We discuss the value of prospective and cross‐sectional imaging in assessing cognition and review volumetric magnetic resonance studies with progressive ipsilateral hippocampal atrophy identified to correlate with seizure frequency. Finally, we consider the use of positron emission tomography biomarkers, such as tau tracers, and connectivity studies that may examine in vivo pathways and further explore cognitive decline in TLE.     

Neuropathological features of mesial temporal sclerosis: Histochemical studies of surgically resected specimens from patients with temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common pathological finding in temporal lobe epilepsy (TLE), but the relationship between MTS and hyperexcitability has not been defined. The neuropathological findings of MTS on the basis of our histochemical investigations using surgically resected specimens from patients with intractable TLE will be reviewed and discussed. Various sclerotic changes including neuronal loss and astrogliosis were observed not only in the hippocampus but also in the other mesial temporal structures such as the amygdala and entorhinal cortex. Moreover, aberrant residual pyramidal neurons were recognized, which showed morphological abnormalities; abnormal distribution of zinc, γ-aminobutyric acid-A receptor and glutamate decarboxy-lase; and disorganization of the granule cell layer (dispersion and bilaminar distribution). Increases in density of the corpora amylacea and peripheral type benzodiazepine receptor binding corresponded with glial proliferation. Histochemical studies demonstrated the association of mossy fiber sprouting with synaptic reorg-anization and changes of several chemically defined inter-neuron systems in the dentate gyrus. Quantitative analysis using in vitro autoradiography showed that neurotrans-mitter receptor bindings related to neuronal excitation (AMPA and NMDA receptor) and inhibition (central type benzodiazepine receptor) were reduced differently as a function of neuronal loss in MTS. These cytochemical changes associated with neurotransmitters and their receptors in the sclerotic hippocampus may constitute the pathological background of epileptogenesis in TLE.     

伴海马硬化的颞叶内侧癫痫的外科治疗(附22例临床分析)

目的探讨伴海马硬化的颞叶内侧癫痫的手术疗效。方法对22例术前诊断伴海马硬化的颞叶癫痫患者,在术中脑电监测下行颞前叶及颞叶内侧结构切除术。结果术后病理诊断均为海马硬化。术后无重大并发症,随访均无癫痫发作。结论伴海马硬化的颞叶内侧癫痫的手术效果良好,确诊后应尽早手术治疗。     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

Default mode network abnormalities in mesial temporal lobe epilepsy: A study combining fMRI and DTI

Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender‐ and age‐matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between‐group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Antiepileptic drug treatment in seizure-free mesial temporal lobe epilepsy patients with hippocampal sclerosis following selective amygdalohippocampectomy

Retrospectively we analysed postoperative AED treatment in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) who were seizure free following selective amygdalohippocampectomy (AHE). In this subgroup, we compared the patients without AEDs with that in the entire series. RESULTS: During the year prior to surgery, in the MTLE-HS group, a mean of 2.3 +/- 0.8 AEDs were taken. The percentage of seizure-free MTLE-HS patients without AEDs increases to 40% from the postoperative year 5 on. In the ILAE Class 1a (seizure- and aura-free since surgery) at postoperative year 5 more than 60% and from postoperative year 7 on more than 90% have discontinued AED intake. CONCLUSION: These figures indicate that reduction and discontinuation of AEDs is the same in the subgroup "seizure-free MTLE-HS patients" compared to the entire series.     

Immunopathology in drug resistant mesial temporal lobe epilepsy with different types of hippocampal sclerosis

Purpose: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types.

Methods: 22 patients who had undergone epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to N-methyl-D-aspartate receptors (NMDAR), leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid B receptor (GABA_BR) and glutamic acid decarboxylase (GAD). Pathological and immunohistochemical investigations including neuronal nuclei (NeuN), NMDAR, GAD, glial fibrillary acidic protein (GFAP), CD8⁺-CD3⁺ lymphocytes and immunoglobulin G (IgG) were done. Patients were grouped according to type of HS. Clinical features and immunohistochemical changes were defined in these groups.

Results: Available sera of 15 patients did not have any neuronal antibodies. Thirteen of 22 patients had HS type 1, three had HS type 2 and two had HS type 3. According to immunohistochemical investigations CD3⁺ and CD8⁺ T cell infiltration was more prominent in the hippocampus of patients with classical HS (International League Against Epilepsy (ILAE) Type 1 HS) and there was a significant negative correlation between epilepsy duration and numbers of CD3⁺-CD8⁺ lymphocytes in temporal lobe parenchyma.

Conclusion: The role of T cell-mediated immunopathology and immunopathological difference in a variety of drug resistant TLE-H2S patients was suggested. These findings can be helpful in understanding the epileptogenicity of HS.