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.     

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.     

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.     

Short-term cognitive changes after surgery in patients with unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis

We investigated the short-term postoperative cognitive function of patients with unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS). Fourteen unilateral MTLE/HS patients who had undergone selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) were enrolled. Cognitive functions related to the frontal and temporal lobes were evaluated using a battery of neuropsychological tests administered before surgery and 3 months after surgery. The battery included the Verbal Fluency Test (VFT), Boston Naming Test (BNT), Stroop Color-Word Test (TST), Trail Making Test (TMT) and Wechsler Memory Scale (WMS). MTLE/HS patients demonstrated significantly improved postoperative performance on the TST regardless of the surgical method or side of resection. There was no significant difference in any of the other neuropsychological tests before and after surgery. After left-side resection, performance on the VFT and the TMT-B was worse than at baseline. After right-side resection, performance on the VFT and WMS short-term memory improved; however, these differences were not statistically significant. SAH patients exhibited improved TST performance but worse TMT-A performance; however, performance on all tests was not significantly different after surgery in ATL patients. In summary, MTLE/HS patients demonstrated improved frontal lobe-related cognitive function after surgery, but no such improvement in temporal lobe-related function was observed. Based on cognitive evaluation, right-sided MTLE/HS patients may be more appropriate surgical candidates than left-sided MTLE/HS patients. SAH may not be better than ATL in improving cognitive function. We hypothesise that postoperative cognitive changes depend on whether the excised cerebral regions are related to the neuropsychological functions examined by specific assessment instruments.     

Initial delta and delayed theta/alpha pattern in the temporal region on ictal EEG suggests purely hippocampal epileptogenicity in patients with mesial temporal lobe epilepsy

ObjectiveTo determine whether the ictal scalp EEG findings suggest purely hippocampal epileptogenicity in patients with mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS).MethodsTwenty-three patients with mTLE with pathologically confirmed HS were divided into 12 with epileptogenicity only in the hippocampus (HS only group) and 11 with epileptogenicity in both the hippocampus and temporal neocortex or other locations (HS plus group), based on the combination of surgical procedures, postoperative outcome, and pathological findings. Sixteen underwent selective amygdalohippocampectomy (SelAH) and 7 received anterior temporal lobectomy. Ictal scalp EEG findings of 79 focal impaired awareness seizures were compared between the HS only and HS plus groups. We focused on the 1–4 Hz rhythmic delta activity at ictal onset followed by 5–9 Hz rhythmic theta/alpha activity 10–30 s after the onset in the temporal region.ResultsThe initial delta and delayed theta/alpha (ID-DT) pattern was observed in 8 of 12 patients in the HS only group, but in none of 11 patients in the HS plus group (p < 0.01).ConclusionsID-DT pattern on ictal EEG suggests purely hippocampal epileptogenicity in mTLE with HS.SignificancePatients with the ID-DT pattern are likely to become seizure-free after SelAH.     

Clinical implications of scalp ictal EEG pattern in patients with temporal lobe epilepsy

ObjectiveTo determine the clinical implications of scalp ictal EEG pattern in patients with temporal lobe epilepsy (TLE).MethodsScalp EEG ictal patterns were retrospectively determined in 27 consecutive patients with medically refractory temporal lobe epilepsy who underwent phase-1 scalp video-EEG and phase-2 simultaneous scalp and intracranial video-EEG recordings for pre-surgical evaluation.ResultsOf the 192 temporal lobe seizures recorded during phase-1 and phase-2 scalp video-EEG studies, 124 (65%) seizures were associated with theta/alpha (5–9 Hz) ictal onset pattern, and 68 (35%) seizures were associated with delta (2–5 Hz) ictal onset pattern. Fourteen (52%) patients had exclusively theta/alpha ictal onset, 3 (11%) patients had exclusively delta ictal onset, and 10 (37%) patients had mixed theta/alpha and delta ictal onsets. MTLE was observed in 26 patients who had 124 seizures with theta/alpha ictal onset and 59 seizures with delta ictal onset. LTLE was observed in one patient who had 9 seizures with delta ictal onset. Scalp ictal EEG pattern was not significantly correlated with postsurgical seizure outcomes.ConclusionsBoth scalp delta and theta/alpha ictal onset patterns can be commonly found in patients with MTLE.SignificanceScalp delta ictal onset is not a unique EEG pattern for LTLE as commonly believed.     

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.     

Interictal EEG and ictal scalp EEG propagation are highly predictive of surgical outcome in mesial temporal lobe epilepsy

PURPOSE: Surgical outcome in patients with mesial temporal lobe sclerosis (MTS) is worse than that in patients with temporal lobe activity (TLE) with tumors. Previous studies of the ictal EEG focused on ictal EEG onset in scalp EEG or ictal EEG propagation in invasive recordings. Ictal EEG propagation with scalp electrodes has not been reported. METHODS: Ictal scalp EEG propagation patterns were studied in 347 seizures of 58 patients with MTS or nonlesional TLE. Interictal epileptiform discharges (IEDs) and the presence of unilateral mesial temporal lobe atrophy in magnetic resonance imaging (MRI) also were studied in these 58 patients. Forty-nine patients were operated on (minimal follow-up of 1 year). RESULTS: Postoperatively, seizure-free outcome was seen in (a) 82.8% of patients with regionalized EEG seizure without contralateral propagation, but in only 45.5% of patients with contralateral propagation (p = 0.007); (b) 84.6% of patients with 100% IED lateralized to one temporal lobe, but in only 52.2% with <100% unitemporal IED (p = 0.015); (c) 88.9% with 100% unitemporal IED and regionalized ictal EEG combined, 73.7% with one of both variables, and only 33.3% with <100% ipsitemporal IED combined with contralateral ictal EEG propagation (p = 0.007). CONCLUSIONS: Switch of lateralization or bitemporal asynchrony in the ictal scalp EEG and bitemporal IED are most probably an index of bitemporal epileptogenicity in MTS and are associated with a worse outcome.     

Late-onset temporal lobe epilepsy with unilateral mesial temporal sclerosis and cognitive decline: A diagnostic dilemma

We present a patient with new onset temporal lobe epilepsy and cognitive decline in his sixth decade with unilateral hippocampal atrophy on structural brain imaging, compatible with mesial temporal sclerosis. This unusual clinical scenario presented a challenging differential diagnosis since it may overlap with primary cognitive disorders, including early-onset Alzheimer's disease and some forms of frontotemporal dementia, and the recently elucidated syndrome of non-paraneoplastic limbic encephalitis associated with voltage-gated potassium channel antibodies.     

发作期直流电漂移与难治性伴海马硬化内侧颞叶癫痫的相关性研究

目的探讨发作期直流电漂移(ictal DC shift)在难治性伴海马硬化的内侧颞叶癫痫(MTLE-HS)中的定位价值。方法回顾性分析18例MTLE-HS患者的临床资料,进行非侵袭性和侵袭性术前评估,对发作起始区分别使用传统频段颅内电极脑电(iEEG)技术和基于宽频脑电技术的ictal DC shift进行定位,比较两组之间的时空分布差异及其与术后病理和预后之间的关系。结果 Ictal DC shift组空间分布明显较iEEG组更为局限,时间分布晚于iEEG组。结论 Ictal DC shift可能为致痫灶的电生理标志物。     

耐药性颞叶内侧癫痫发作前期海马脑电特征分析

目的 观察耐药性颞叶内侧癫痫患者发作前期海马电极脑电活动特点,为判断和切除癫痫病灶提供神经电生理学依据.方法 对16例非侵入性手段难以明确病灶的耐药性颞叶内侧癫痫患者进行双侧海马电极监测,患者停用抗癫痫药在非麻醉状态下监测48～72 h,分析癫痫发作前期海马电极脑电图资料,探讨耐药性颞叶内侧癫痫发作前期海马电极脑电活动特点.结果 16例发作间期记录到背景活动基础上出现局限于某几个电极点的阵发性高幅慢波1例、发作性快波节律1例、棘波或棘尖慢复合波14例,视为异常脑电活动;经过48～ 72 h监测,10例监测到33次临床癫痫发作,发作起始期海马电极均可记录到清晰可辨的癫痫样脑电波形.结论 颞叶内侧癫痫临床发作起始期海马电极癫痫样放电清晰可辨,部位局限,易于确定癫痫性活动起源部位.对于非侵入性手段难以判断癫痫样放电起源的颞叶内侧癫痫可采用脑立体定向技术植入海马深部电极进行脑电监测.     

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.     

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.     

Magnetic resonance imaging follow-up of progressive hippocampal changes in a mouse model of mesial temporal lobe epilepsy

PURPOSE: Hippocampal sclerosis (HS) is the most frequent lesion found in mesial temporal lobe epilepsy (mTLE). MR imaging is considered to be the most sensitive and specific method to detect HS. Despite extensive studies performed on humans and except in a recent study, the morphologic pattern of HS is usually analyzed when the disease has already fully developed, thus not allowing any insight into the mapping of the progressive morphologic changes inducing the development of mTLE. We have recently characterized a model of mTLE that reproduces the unilateral pattern of HS, induced by intrahippocampal injection of low doses of kainate (KA) in mice. METHODS: In this study, we monitored the temporal evolution of the development of HS in this model of mTLE by using T2-weighted sequence, T2-relaxation time measurements, and T1-weighted spin-echo technique after injection of gadolinium, from 1 h to 120 days after KA injection. RESULTS: HS induced by intrahippocampal KA injection occurred in two phases. First, we observed a transient hyperintense T2-weighted signal in the cortex above the injected hippocampus, most likely indicative of vasogenic edema partly due to the neurotoxic effect of KA. The concomitant increase in the T2 signal in the injected hippocampus and ipsilateral amygdala likely reflects the phase of cytotoxic edema occurring probably in relation to the excitotoxic consequences of both KA and seizure activity. Second, from 15 days on, a persistent unilateral increased T2 signal was detected in the hippocampus, which most probably reflects gliosis. CONCLUSIONS: Our findings indicate that longitudinal follow-up would permit a better understanding of the mechanisms underlying the constitution of HS in humans and eventually development of prevention strategies.     

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。     

选择性杏仁核-海马切除术对内侧颞叶癫痫病人神经心理学的影响

目的 探讨选择性杏仁核-海马切除术（SAH）对内侧颞叶癫痫病人认知功能的影响。方法 回顾性分析2009年1月~2017年5月接受SAH治疗的67例内侧颞叶癫痫的临床资料,术前、术后3个月和术后1年均行详细的神经心理学评估,包括智商、记忆商和语言功能。结果 36例行左侧SAH,31例行右侧SAH。术后1年,癫痫控制效果达到Engel分级Ⅰ级50例,Ⅱ级7例,Ⅲ级8例,Ⅳ级2例。术后3个月,左侧手术病人言语功能、记忆商较术前明显降低（P<0.05）,右侧手术病人言语理解指数、语义流畅性测验明显改善（P<0.05）;术后1年,无论是左侧手术病人,还是右侧手术病人,智商、记忆商、言语功能较术后3个月略改善（P>0.05）;手术前后视觉记忆均无明显变化（P>0.05）。结论 海马硬化性内侧颞叶癫痫行SAH后,左侧手术病人会出现比较明显的言语和记忆功能减低。     

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.