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.     

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.     

Impaired facial emotion recognition in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS): Side and age at onset matters

To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age at onset <6 years) vs. late-onset, and before vs. after AMTL. After controlling for years of education, duration of epilepsy and number of antiepileptic drugs (AEDs) taken, on multivariate analysis, fear recognition was profoundly impaired in early-onset right MTLE-HS patients compared to other MTLE patients and control subjects. Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations.     

氢质子磁共振波谱与颞叶癫癎

氢质子磁共振波谱（^1H—MRS）是目前唯一一种无创性的测定活体体内化学代谢物改变的影像捡查技术，近年已广泛应用于颞叶癫癎（TLE）的研究。^1H—MRS是以非介入的方法在组织学水平上研究TLE的病变组织，可对TLE患者定侧、定位诊断以及预后等方面提供重要的依据。本义对^1H—MRS任TLE的应用研究进展予以介绍。     

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.     

Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS)

Purpose :  To assess the prevalence and attributes of atypical language lateralization (ALL) in patients with left mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS).
Methods :  We recruited consecutive patients with left MTLE-HS, who had undergone resective surgery and had pathologically proven HS. Based on the Wada test, language lateralization was classified into typical (left hemispheric) or atypical (right hemispheric or codominant). We assessed the attributes of patients with ALL using univariate and multivariate analyses.
Results :  Of 124 patients with left MTLE-HS, 23 (18.5%) had ALL. ALL occurred more frequently in patients with severe initial precipitating injury (IPI), early onset of epilepsy, and a short latent period between IPI and onset of habitual seizures. ALL was more common in patients with bitemporal and extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On multivariate analyses, the age at onset of habitual seizures <6 years, atypical IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities independently predicted ALL. The likelihood of ALL was very low (∼1%) when all of these four risk factors were absent, whereas it was very high (>95%), if any three or all four of them were present.
Conclusions :  ALL occurs in one-fifth of patients with left MTLE-HS. ALL is more frequent in those with structural or functional extrahippocampal involvement and early onset of epilepsy interrupting the development of normal language networks. Because ALL is uncommon in those with damage/dysfunction restricted to the hippocampus, the hippocampus itself may have only a limited role in determining language lateralization.     

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.     

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis

OBJECTIVES: To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. METHODS: The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. RESULTS: At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. CONCLUSIONS: The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.     

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.     

Electrical stimulation of the ventral hippocampal commissure delays experimental epilepsy and is associated with altered microRNA expression

BackgroundUp to 80% of mesial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS) are resistant to pharmacological treatment, often necessitating surgical resection. Deep brain stimulation (DBS) has emerged as an alternative treatment for patients who do not qualify for resective brain surgery. Brain stimulation may also exert disease-modifying effects, and noncoding microRNAs have recently been proposed to shape the gene expression landscape in epilepsy.ObjectiveWe compared the effect of DBS of 4 different hippocampal target regions on epileptogenesis and manifest epilepsy in a rat model of mTLE-HS. To explore mechanisms, we profiled the effect of the most effective DBS paradigm on hippocampal microRNA levels.MethodsMTLE-HS was induced by electrical stimulation of the perforant pathway (PP) in rats. This paradigm leads to spontaneous seizures within 4 weeks. We investigated DBS of 4 targets: PP, fimbria fornix (FF) formation, dentate gyrus (DG) and ventral hippocampal commissure (VHC). We applied both high- (130 Hz) and low-frequency (5 Hz or 1 Hz) stimulation. Functional microRNAs were identified in the hippocampus immediately after VHC-DBS and after a 97-day recording period by sequencing small RNAs bound to Argonaute-2, a component of the miRNA silencing complex.ResultsLow frequency DBS of the VHC significantly delayed the occurrence of the first spontaneous recurrent seizure in the PPS model by ∼300%, from 19 to 56 days. No other stimulation regime altered the latency phase. Upregulation of 5 microRNAs during epileptogenesis was suppressed by VHC-stimulation.ConclusionWe conclude that DBS of the VHC delays epilepsy in the PPS model in rats and is associated with differential regulation of several miRNAs. Additional studies are required to determine whether VHC-regulated miRNAs serve causal roles in the anti-epileptogenic effects of this DBS model.     

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.     

A Long-Term Follow-Up Study of First Episodes of Idiopathic Status Convulsivus in Childhood: In Relation to Subsequent Epilepsy (Second Report)

Abstract: Fifty-four idiopathic status convulsivus (SC) cases were followed prospectively for a period between 5 :and 21 :years, the average being 13 :years. Three-fourths of the cases had no residuals. There were two patterns of subsequent epilepsy; 1) complex partial seizures (CPS) with or without secondarily generalization (GTS) developed 4.3 ± 3.5 years after febrile SC, 2) unilateral seizures or CPS ± GTS developed 1.2 ± 1.0 years after afebrile SC. The seizure prognosis of these cases was good except for some cases in the former group. There have been two kinds of theories regarding SC and epilepsy until now. One was derived from retrospective studies: SC and/or complex febrile convulsion (FC) were considered the main causes of temporal lobe epilepsy (TLE) producing mesial temporal sclerosis (MTS). Another was derived from prospective studies, in which the relation between FC and TLE was considered weak. Our results revealed that 6 :cases (15%) out of 30 :febrile SC developed epilepsy, and that five of those six cases were diagnosed as CPS. Three of 5 :CPS cases were diagnosed as TLE. Recently the seizure prognosis of operative therapy for TLE—especially the MTS type—has been very favorable. Furthermore, it has become easy to And MTS by Magnetic Resonance Imaging (MRI). So, we emphasize that a precise follow-up study of SC using MRI, EEG, etc., is important in deciding the appropriate therapy for TLE, as well as in the study of the pathogenesis of TLE.     

Psychiatric Symptoms in Temporal Lobe Epilepsy with Left Mesial Hippocampal Sclerosis

A 16-year-old woman was referred to us for depression and persistent suicidal and homicidal ideation. From 2010, the patient visited a neurologist due to recurrent grand mal epilepsy, auditory and visual hallucinations, episodic memory loss, and persistent depression. Upon admission, it was revealed through clinical history taking that she had suffered from chronic bullying from same-sex peers and sexual abuse, twice, from an adult male in the neighborhood when she was 10 years old. A brain magnetic resonance imaging study showed left mesial hippocampal sclerosis. The patient exhibited improvement of her psychiatric symptoms after treatment with a combination of fluoxetine (30 mg) and aripiprazole (10 mg). Children and adolescents with epilepsy experience conflicts in the family, challenges at school, stigma, and psychosocial limitations or deprivations due to their comorbid psychiatric symptoms and hence, psychiatric evaluation and early intervention is important when treating these patients.     

Memory characteristics in mesial temporal lobe epilepsy: Insights from an eye tracking memory game and neuropsychological assessments

Aims

To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls.

Methods

Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker.

Results

Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = −0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05).

Conclusion

Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring.     

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。     

Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

MethodsVBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients.ResultsIn SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups.ConclusionsOur study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.     

Mesial temporal sclerosis and volumetric investigations

Volumetric MRI data acquisition permits reliable and accurate measurement of mesial temporal lobe structures. In normal subjects, these structures are very symmetric. A high degree of pathological specificity is associated with the finding of even minor volume asymmetries. Definition in this manner allows precise estimation of both absolute and relative volume differences, and precise anatomical localisation of volume loss within the hippocampus. There are good EEG and clinical correlates with the distribution of volume loss defined on MRI studies. Volumetric assessment is fast, reliable, non-invasive, and a relatively inexpensive component of the pre-operative work-up. It is the method of choice when imaging patients with clinical temporal lobe epilepsy undergoing pre-surgical evaluation. The finding of significant hippocampal volume asymmetry in a patient with clinical temporal lobe seizures being evaluated for epilepsy surgery may obviate the need for alternative sophisticated, invasive, or expensive investigative procedures. At our centre, such MRI allows "fast track" cases to proceed to surgery without further invasive investigations, and is likely to have a dramatic effect on pre-operative evaluation in most centres practising epilepsy surgery.     

Familial mesial temporal lobe epilepsy (FMTLE)

Introduction Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. Patients and methods FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. Results Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. Discussion FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.