小儿顽固性颞叶癫痫的病理特点研究

目的 研究小儿顽固性颞叶癫痫的临床病理学表现.方法 80例小儿顽固性颞叶癫痫患者行标准前颞叶切除术,切除组织送病理学检查.术后随访1-5年,根据Engel分级评估手术效果.结果 切除组织病理学表现以单纯海马硬化(26例)、良性肿瘤(20例)、局灶性皮层发育不良(10例)和海马硬化合并颞叶其他病变(9例)四大类型为主.癫痫发作控制结果提示EngelⅠ级58例,Ⅱ级11例,Ⅲ级6例,Ⅳ级5例.结论 小儿顽固性颞叶癫痫病理表现多样,以海马硬化、良性肿瘤和局灶性皮层发育不良最常见;颞叶切除疗效肯定;病理类型与手术效果之间的关系仍待更多研究.     

Outcome of surgical treatment in familial mesial temporal lobe epilepsy

PURPOSE: To describe postoperative outcome in patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: We studied FMTLE patients who underwent surgical treatment for refractory seizures. FMTLE was defined when at least two individuals in a family had a clinical EEG diagnosis of MTLE. Preoperative investigation included magnetic resonance imaging (MRI), interictal/ictal EEGs, and neuropsychological evaluation. We used Engel's classification for postoperative outcome. RESULTS: To date, 20 FMTLE patients have been operated on, with 1.6 to 9.8 years of follow-up (mean, 5.5 years). Hippocampal atrophy (HA) and other signs of mesial temporal sclerosis (MTS) were present in 18 patients (15 unilateral). Seizures were recorded in 19 patients. Seventeen (85%) patients are in class I. Two patients had normal hippocampal volumes (HcV): one (5%) is in class II and the other (5%) in class IV (extratemporal seizures developed after surgery). One (5%) patient had bilateral HA and is in class III. Qualitative histopathology showed MTS with different degrees of severity. CONCLUSIONS: Refractory FMTLE patients have good surgical outcome when unilateral or clearly asymmetric HA is identified. Preoperative investigation should be the same as that in patients with sporadic refractory MTLE.     

Subtle microscopic abnormalities in hippocampal sclerosis do not predict clinical features of temporal lobe epilepsy

PURPOSE: Subtle microdysplastic features are found in some patients with hippocampal sclerosis (HS) and refractory temporal lobe epilepsy. The significance of these findings is unknown. We investigated their frequency, relation to the pattern of HS, and clinical associations. METHODS: One-hundred forty patients with histologically confirmed HS (mean age at operation, 35 years; 85 women) were analyzed. The presence of HS and subtle structural abnormalities (SSAs) in the mesial temporal lobe and in the lateral neocortical tissue was assessed in detail. Antecedents, seizure characteristics, two verbal memory tests, and outcome in HS patients with and without SSAs were determined. RESULTS: SSAs were found in 60 (43%) of the 140 HS patients, being mesial only in 32 of the 60 cases, and lateral only in nine cases; the remaining 19 cases had both mesial and lateral abnormalities. The frequency of SSA was not related to the pattern of HS or other tested variables. Prolonged febrile convulsions were present in 26 (44%) patients with SSAs, and in 26 (34%) patients (not significant) without SSAs. The outcome after surgery did not differ between patients with SSAs (incidence rate ratio for seizure recurrence, 0.9; 95% confidence interval, 0.5-1.6) compared with patients without SSAs (reference ratio, 1). CONCLUSIONS: Forty-three percent of HS patients have SSAs in their lobectomy specimens. The presence of SSAs does not predict clinical characteristics, such as presence of prolonged febrile convulsions, postsurgical outcome, or neuropsychological performance, nor does it correlate with the histologic pattern of HS.     

Neuropathological findings in 224 patients with temporal lobe epilepsy

During the period between 1976 and 1990, 247 patients with pharmaco-resistant complex partial seizures and a documented unilateral epileptogenic area in the mediobasal temporal lobe underwent a selective amygdalo-hippocampectomy procedure at our institution. Biopsy specimens from 224 patients (91% of the total) were available for a retrospective histopathological and immunohistochemical review. The tissue specimens of 23 patients without evidence for a macroscopic lesion have been used for neurochemical studies and could not be evaluated histopathologically. The most common temporal lobe pathology were neoplasms in 126 patients, i.e. 56%. Tumor entities observed included 23 astrocytomas (18% of all tumors), 17 gangliogliomas (13%), 15 oligodendrogliomas (12%), 15 cases of glioblastoma multiforme (12%), 13 pilocytic astrocytomas (10%), 12 oligo-astrocytomas (10%), 11 anaplastic astrocytomas (9%) and 20 tumors of various other histologies. In 23 specimens (10%), small foci of oligodendroglia-like clear cells were found. The frequent association of these foci with low-grade gliomas or neural hamartomas raises the possibility that these structures may serve as precursor lesion for neuroepithelial tumors of the temporal lobe. In 98 cases, pathological changes of non-neoplastic origin were encountered. The most common diagnoses in this group included hippocampal gliosis/sclerosis (49 cases, 22%) and vascular malformations (20 cases, 9%). Hamartomas, i.e. focal accumulations of dysplastic neuro-glial cells were diagnosed in 14 patients (6%). In only four cases have we not been able to detect any microscopic pathology. These results indicate that a high proportion of pharmaco-therapy-resistent complex-partial seizures are caused by neoplasms of the temporal lobe, some of which appear to the strikingly overrepresented in this group of patients.     

Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study

PURPOSE: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug-resistant epilepsies of mesial temporal lobe origin. METHODS: From July 1996 to March 2000, three European centers selected 21 patients with mesial temporal lobe epilepsy (MTLE) for a temporal lobectomy. The preoperative investigations included video-EEG with foramen ovale electrodes, magnetic resonance imaging, neuropsychological testing, and the ESI-55 quality-of-life questionnaire. In place of a cortectomy, radiosurgical treatment was performed by using the Leksell Gamma Knife (LGK) at a dose of 24 +/- 1 Gy at the margin. The target included the anterior parahippocampal cortex and the basal and lateral part of the amygdala and anterior hippocampus (head and body). One patient (a heavy smoker) died of a myocardial infarction. Twenty patients were available for prospective evaluation. A minimum 2-year follow-up period included clinical, neuropsychological, and radiologic evaluations. RESULTS: At each 6-month follow-up evaluation, the frequency of seizures was significantly smaller than that at the previous visit. The median seizure frequency of 6.16 the month before treatment was reduced to 0.33 at 2 years after treatment. At 2 years, 65% of the patients (13 of 20) were seizure free. Five patients had transient side effects, including depression, headache, nausea, vomiting, and imbalance. There was no permanent neurological deficit reported except nine visual field deficits. No neuropsychological deterioration was observed 2 years after treatment. The quality of life was significantly better than that before surgery. CONCLUSIONS: The safety and efficacy of the radiosurgical treatment of MTLEs appears good in this group of patient over short-to-middle term. Delay of the seizure cessation was the major disadvantage of GKS. A longer follow-up period is required for confirmation of these results.     

颞叶癫痫患者海马硬化神经元脱失的亚群特点

目的探讨颞叶癫痫患者海马硬化神经元脱失的亚群特点。方法颞叶癫痫患者中8例海马硬化和7例非海马硬化，以正常海马解剖为对照，观察两患者组海马各亚群神经元脱失情况。结果海马硬化组和非海马硬化组均有CA1、CA3锥体细胞和颗粒细胞脱失，海马硬化组明显。门区神经元脱失仅在海马硬化组可见。结论颞叶癫痫患者海马结构主要细胞脱失，门区神经元脱失是海马硬化的主要特点。海马硬化的形成与齿状回尤其是门区神经元的关系更为密切。     

Outcome predictors for surgical treatment of temporal lobe epilepsy with hippocampal sclerosis

Purpose: To study long-term postoperative course and identify predictors for postoperative seizure control in patients with medically intractable temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS), diagnosed by magnetic resonance imaging (MRI), and ascertained histopathologically. To compare patients becoming seizure-free (i.e., cured from epilepsy) and patients experiencing prolonged seizure-free periods interposed with recurring seizures.
Methods: One hundred thirty-five patients (74 women) underwent complete evaluation for epilepsy surgery. The predictive value of duration of epilepsy, age at onset, age at surgery, gender, febrile convulsion history, ictal dystonic posturing, unilateral interictal electroencephalography (EEG) discharges (IED), preoperative secondarily generalized tonic–clonic seizures (SGTCS), and preoperative seizure frequency for short- and long-term postoperative seizure control were evaluated with two classification systems: Classification 1 (seizure-freedom with or without auras during 12-months before observation points) and the stringent classification 2 [International League Against Epilepsy (ILAE) Ia; absolute absence of seizures and auras after operation].
Results: Unilateral IED at year 1 and 2 (p = 0.037 and p = 0.034), male gender and low seizure frequency at year 2 (p = 0.013 and p = 0.046) were significant predictors for seizure freedom using classification 1. All variables (except male gender at year 2; p = 0.035) lost their predictive power, applying classification 2. The proportion of seizure-free patients remained stable between 70% to 79% with classification 1, but decreased from 64.4% at year 1 to 45.8% at year 5 with classification 2.
Discussion: Positive predictors of short-term outcome do not predict long-term outcome in patients with TLE associated with HS. Absolute freedom of seizures and auras cannot be predicted by conventional preoperative variables.     

Interictal and postictal circadian and ultradian luteinizing hormone secretion in men with temporal lobe epilepsy

PURPOSE: Hypothalamic regulation of the reproductive axis in temporal lobe epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing hormone (LH), has been shown to be altered interictally and postictally. Our objective is to determine if epilepsy or seizures disrupt normal circadian fluctuations of LH as well as circadian organization of ultradian bursts of LH. METHODS: We characterized LH secretion in 10 men with TLE during two 24-h blocks: an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was measured every 10 min and characterized by circadian and ultradian patterns with cosinor and deconvolution analysis. RESULTS: Mean peak serum concentrations of LH occurred at approximately 0400 in controls, were significantly delayed approximately 5 h interictally, and were randomly distributed postictally. Burst amplitudes differed significantly by phase among controls, with the largest amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase differences were present in interictal or postictal epochs. Burst frequency weakly but significantly was slowest between 0101 and 0700 in controls, but did not differ significantly by phase in either interictal or postictal epochs. Postictal LH burst frequencies, but not amplitudes, were significantly decreased immediately postictally. CONCLUSION: The pulsatile secretion of LH in TLE is abnormal both in the circadian as well as the ultradian domain. Interictal effects consist mainly in loss of circadian fluctuations in LH burst amplitude, whereas postictal effects consist of altered burst timing. Altered daily patterns of neuroendocrine signals may underlie other disorders of homeostasis in TLE.     

家族性颞叶癫痫的临床与脑电图特征分析

目的探讨家族性颞叶癫痫(FTLE)的临床和脑电图(EEG)特点。方法收集6个 FTLE的家系资料,通过详细的调查,建立较完善的家系谱,并对受累者的临床资料、EEG进行分析总结。结果6个家系共78名家族成员,其中受累者20例,每个家系2-6例受累者不等,2代发病居多。发病年龄0．5-27岁,平均(13．7±10．5)岁。平均发作频率(6．7±8．9)次/月。表现为复杂部分性发作13 例次(76．5％),继发全身强直一阵挛性发作12例次(70．6％),单纯部分性发作4例次(23．5％),强直发作和全身强直一阵挛性发作各1例次;无法分类3例。20例受累者中3例出现复杂视幻觉,1例出现听幻觉。受累者中13例进行发作间期EEG检查,仅1例示颞叶局灶痫性放电(7．7％),2例痫性异常放电, 余未见明显异常;10例进行MRI检查,仅1例示右额颞发育异常(10．0％)。18例受累者疗效观察,3例发作自然缓解,另15例接受抗癫痫药物(AEDs)治疗,14例有效(4例发作控制),仅1例无效。结论 FTLE家庭受累者临床症状呈多样性,发作间期EEG大部分未见局灶异常放电,MRI检查未见异常。 FTLE的正确诊断主要依据患者临床发作特征和家系谱,AEDs治疗疗效良好。     

Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy

PURPOSE: To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). METHODS: Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. RESULTS: Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. CONCLUSIONS: This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.     

Stereologic estimation of hippocampal GluR2/3- and calretinin-immunoreactive hilar neurons (presumptive mossy cells) in two mouse models of temporal lobe epilepsy

Purpose: Hippocampal mossy cells receive dense innervation from dentate granule cells and, in turn, mossy cells innervate both granule cells and interneurons. Mossy cell loss is thought to trigger granule cell mossy fiber sprouting, which may affect granule cell excitability. The aim of this study was to quantify mossy cell loss in two animal models of temporal lobe epilepsy, and determine whether there exists a relationship between mossy cell loss, mossy fiber sprouting, and granule cell dispersion. Methods: Representative hippocampal sections from p35 knockout mice and mice with unilateral intrahippocampal kainate injection were immunolabeled for GluR2/3, two subunits of the amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor and calretinin to identify mossy cells. Mossy fibers were immunostained against synaptoporin. Key Findings: p35 Knockout mice showed no hilar cell death, but moderate mossy fiber sprouting and granule cell dispersion. In the kainate‐injected hippocampus, there was an 80% and 85% reduction of GluR2/3‐ and GluR2/3/calretinin‐positive hilar neurons, respectively, and dense mossy fiber sprouting and significant granule cell dispersion. In the contralateral hippocampus there was a 52% loss of GluR2/3‐, but only a 20% loss of GluR2/3‐calretinin‐immunoreactive presumptive mossy cells, and granule cell dispersion; no mossy fiber sprouting was observed. Significance: These results indicate a probable lack of causality between mossy cell death and mossy fiber sprouting.     

24例难治性颞叶癫痫手术患者病例分析

目的 了解难治性颞叶癫痫手术治疗的现状和预后效果.方法 回顾性分析2011年4月-2014年6月于淄博昌国医院经手术治疗且临床及随访资料完整的24例难治性颞叶癫痫手术患者,其中男14例,女10例.年龄16～44岁,平均(24.40±6.26)岁,平均病程(12.50±8.42)年.分析患者的临床特点和预后情况.结果 2...     

Surgical treatment for refractory temporal lobe epilepsy in the elderly: seizure outcome and neuropsychological sequels compared with a younger cohort

PURPOSE: Surgical treatment of refractory temporal lobe epilepsy (TLE) is promising for selected patients, but only little experience has been acquired in operating on older patients, especially with limited resections. We intend to delineate clinical and surgical factors influencing outcome in patients older than 50 years at operation and to compare the results with those of a younger patient cohort. METHODS: Fifty-two patients older than 50 years were operated on for intractable mesial or combined mesiolateral TLE between 1991 and 2002. The mean age at operation was 55 years, and the mean duration of epilepsy was 33 years. Forty selective amygdalohippocampectomies (33 for hippocampal sclerosis, seven for removal of a mesiotemporal lesion), five lateral temporal lesionectomies plus amygdalohippocampectomy, and seven anterior temporal lobectomies were performed. Eleven (21%) patients had undergone invasive presurgical video-EEG monitoring. The mean follow-up period was 33 months. We compared the results with those of a younger cohort operated on in the same time period. RESULTS: Thirty-seven older patients attained complete seizure control (71% class I), and 10 patients had only rare postoperative seizures (19% class II). Four patients improved >75% (8% class III), and one patient did not improve (2% class IV). The same rate of seizure control was attained by 11 patients older than 60 years at surgery. These results were not significantly different from those in a younger patient group. A trend toward better seizure control was noted in 16 patients with an epilepsy duration of <30 years (all class I or II), and in 20 patients with a seizure frequency of fewer than five seizures per month (all class I or II). No mortality resulted from a total of 65 diagnostic and therapeutic procedures. A 3.8% permanent neurologic morbidity (dysphasia and hemiparesis) was noted. Hemianopia occurred in three (5.9%) patients. Neuropsychological testing revealed low preoperative performances and some gradual further deterioration after surgery. CONCLUSIONS: Results of surgery for TLE with mainly limited resections are promising in patients older than 50 years and older 60 years, despite the long seizure history. As expected, the risk of complications is somewhat higher compared with that in a younger control group. The impact of low neuropsychological performance is a concern.     

经皮层选择性海马杏仁核切除术治疗颞叶癫痫

目的 观察经皮层入路选择件海马含仁核切除术对颞叶癫痫的治疗效果及风险。方法 20例单侧海马硬化性顽崮性颞叶内侧癫痫患者，采用颢部开颅经颞中同侧脑室入路选择性海马杏仁核切除术治疗，随访至少1年以卜，采用Engel分级量表进行针对癫痫发作控制效果的评价。结果 Ⅰ级结果15例，Ⅱ级结果3例，Ⅲ级结果2例，无明显持久性并发症，无手术死亡。结论 在严格筛选的颞叶内侧癫痫，颞部开颅经颞中回皮层入路选择性切除海马含仁核术对治疗颞叶癫痫，安全有效。     

Increased densities of AMPA GluR1 subunit proteins and presynaptic mossy fiber sprouting in the fascia dentata of human hippocampal epilepsy

In human hippocampal epilepsy, there is a consistent pathology of cell loss and reactive synaptic reorganization of ‘excitatory' mossy fibers (MF) into the inner molecular layer (IML) of the fascia dentata (FD). In this study, neo-Timm's histochemistry of MFs and immunocytochemistry of GluR1 were used to determine, in patients with or without hippocampal sclerosis (HS), if there was a correlation between aberrant supragranular (IML) mossy fiber sprouting and increased densities of AMPA GluR1 subunit proteins in the IML of the FD. Computerized quantified densitometric grey values of Timm and GluR1 densities were corrected for the densities of granule cell losses using cell counts. In the IML of the HS group, despite the losses of granule cells, mossy fiber sprouting was significantly greater (P<0.000001) and GluR1 protein densities were significantly higher (P<0.0005) than those of the non-HS group. Unlike supragranular mossy fiber sprouting, which was limited to the IML, the increased GluR1 stainings were distributed throughout the whole molecular layer. For all cases, MF synaptic reorganization in the supragranular ML was correlated with GluR1 subunit protein densities in the IML (R=0.784, P<0.0093). These data demonstrate that in the human epileptic fascia dentata, there are significantly increased AMPA GluR1 subunit proteins associated with aberrant MF synaptic reorganizations. This suggests that the hyperexcitability of sclerotic hippocampus occurs, at least in part, from the associated changes of both presynaptic mossy fiber glutamatergic neoinnervation and increased GluR1 subunit proteins in the dendritic domains of the FD.