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.     

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.     

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。     

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.     

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。     

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.     

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.     

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.     

Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study

We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype.     

Review: Hippocampal sclerosis in epilepsy: a neuropathology review

Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post‐mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post‐mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long‐term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho‐aetiological subtypes of HS.     

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.     

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.     

伴海马硬化的颞叶癫痫患者的临床特点及手术治疗

目的探讨颞叶癫痫海马硬化的临床特点及手术治疗的效果。方法伴海马硬化的颞叶癫痫患者18例,其中男10例,女8例;年龄12~37岁,病程3~10年。癫痫复杂部分性发作10例,部分性发作继发全身性发作2例,全身强直-痉挛性发作6例。结合患者的临床表现、MRI检查和视频脑电图(V-EEG)监测结果,对这18例患者行前颞叶切除术(包括大部分海马和杏仁核)。结果所有患者术中皮层和深部电极脑电图均发现颞叶皮层海马、杏仁核有异常放电,术后病理检查均证实海马硬化的诊断。术后18例患者均出现发热,但经过抗炎、腰椎穿刺及支持治疗后渐好转。术后1年以上的随访发现16例癫痫发作完全消失,2例术后较术前显著改善,仅偶有癫痫发作,但均长期服用抗癫痫药物。结论对于颞叶癫痫伴有海马硬化的患者,如果同时脑电图又发现有同侧颞叶痫样放电,则可以考虑行该侧前颞叶切除术(包括大部分海马和杏仁核),若手术切除彻底,其术后疗效也较满意。     

Periodic epileptiform discharges in mesial temporal lobe epilepsy with hippocampal sclerosis

PurposePeriodic epileptiform discharges (PEDs) are an uncommon, abnormal EEG pattern seen usually in patients with acute diseases and less frequently in chronic conditions, such as mesial temporal lobe epilepsy (mTLE). Evaluate the clinical histories, neuroimaging findings, and serial electrophysiological studies prior to the appearance of PEDs in patients with mTLE secondary to hippocampal sclerosis (HS).MethodsWe searched 19, 375 EEGs (2006–2012) for the presence of PEDs secondary to mTLE due to HS.Results12 patients were included. The patients with PEDs had a high prevalence of psychiatric comorbilities, including major depression (50%), interictal psychosis (16%) and dementia (8%). All of the patients had intractable epilepsy with similar clinical findings. We observed a sequential neurophysiological worsening of the EEG patterns prior to the appearance of PEDs. Five patients with PEDs underwent epilepsy surgery and four were seizure free at follow-up 15 (±9) months.ConclusionsPEDs are rare in patients with mTLE and HS and their presence in these cases could reflect clinical severity and neurophysiologic worsening, clinically manifested by intractable epilepsy and severe psychiatric comorbidities. The presence of PEDs in EEGs of patients with mTLE, however, was not associated with poor postsurgical seizure-freedom.     

伴海马硬化的颞叶癫痫患者的临床特点分析

目的通过比较伴和不伴海马硬化的颞叶癫痫患者的临床特点,为临床诊治提供依据。方法收集2009年6月至2012年6月期间南京军区南京总医院颞叶癫痫患者144例,通过头颅MRI或颞叶癫痫手术病理分类,对每位患者发作时临床表现、发作间期、起病年龄及脑电图等进行分析。结果伴海马硬化的颞叶癫痫患者起病年龄较不伴海马硬化的颞叶癫痫患者更小,同时更易出现发作前先兆和意识障碍。伴或不伴海马硬化的颞叶癫痫患者的脑电图异常率相似,大多数患者脑电图可发现癫痫样异常改变。海马硬化患者有高热惊厥史的更常见。结论伴有海马硬化的颞叶癫痫患者有一些特殊的临床表现,深入了解伴海马硬化的颞叶癫痫患者的临床特点将利于更好更快地选择颞叶癫痫患者的合理治疗方案。     

Clinical and neuroimaging features of good and poor seizure control patients with mesial temporal lobe epilepsy and hippocampal atrophy

Summary: Purpose: Hippocampal atrophy (HA) and signal changes, detected at magnetic resonance imaging, have been associated with intractable seizures. Such a relation has been established by tertiary centers, where the prevalence of more severe cases tends to be higher. We evaluated the clinical and imaging variables that may have relevance to seizure control in patients with mesial temporal lobe epilepsy (MTLE) and HA. Methods: MTLE patients from the outpatient clinic of University of São Paulo School of Medicine at Ribeirão Preto were evaluated with protocols for the temporal lobe. Patients were considered to have good seizure control (GC; n = 42 ) if they had three of fewer seizures per year. Patients with pharmacoresistance and who did not fit the criteria for GC were considered to have poor seizure control (PC; n = 44 ). We made group comparisons and correlations of clinical data and hippocampal volume (HV) with seizure frequency. Results: No statistical differences were observed between the GC and PC groups in the following parameters: age at the time of study, age at the time of the initial precipitating injury (IPI) or first epileptic seizure, epilepsy duration and follow‐up, and family history of epilepsy. No differences were found in HV between GC (male, 2.04 ± 0.60 cc ; female, 2.00 ± 0.70 cc ) and PC (male, 2.26 ± 0.47 cc ; female, 2.15 ± 0.48 cc ) groups. Regression analysis indicated no correlation between seizure frequency and HV (p = 0.33) . Conclusions:These findings suggest that the intensity of HA does not have a direct correlation with seizure frequency in patients with MTLE with HA and that the detection of HA in MTLE patients does not mean an unequivocal indication of intractability.     

Marked accumulation of oligodendroglia‐like cells in temporal lobe epilepsy with amygdala enlargement and hippocampal sclerosis

Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia‐like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40‐year‐old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus. The patient began to have refractory seizures at the age of 14, and preoperative MRI revealed left amygdala enlargement and left hippocampal atrophy. Other examinations were consistent with left mesial temporal epileptogenicity. He underwent surgical resection and achieved seizure freedom. Histopathological study of the amygdala showed swollen neurons with relatively large bodies and thick neurites, accompanied by vacuolar degeneration in the background. Additionally, there were marked clusters of OLCs with round nuclei and densely stained chromatin around the uncus. The OLCs were Olig2‐positive. In the hippocampus, severe cell loss in CA1 and granule cell dispersion in the dentate gyrus were found. These findings may provide some insights for further pathological investigations of TLE with non‐neoplastic AE.