Hippocampal deformation-based shape analysis in epilepsy and unilateral mesial temporal sclerosis

PURPOSE: To assess shape changes in patients with mesial temporal sclerosis (MTS) and temporal lobe epilepsy (TLE), by using deformation-based hippocampal shape analysis. METHODS: We retrospectively reviewed magnetic resonance imaging (MRI) studies in 30 subjects with unilateral MTS (15 right-sided MTS, 15 left-sided MTS) and TLE. We defined the "average" hippocampus in the right- and left-MTS groups by generating a mean transformation for the 15 deformation images in each group. Further to quantify the difference between the hippocampi, we coregistered the mean transformation of the involved hippocampus (with MTS) to the contralateral hippocampus, considering the left- and right-MTS groups independently. We generated a color "flame" scale showing degrees of outward and inward deviation of the coregistered hippocampi. RESULTS: Both the right- and left-MTS groups showed similar shape changes, with maximal inward deformation in the medial and lateral hippocampal head and the hippocampal tail. However, more extensive involvement was seen in the lateral hippocampal body in the right-MTS group as compared with the left. CONCLUSIONS: Deformation-based hippocampal shape analysis shows specific regions of hippocampal surface anatomy that are most affected in MTS. This technique may aid in detection of clinically significant anatomic abnormalities of the hippocampus in patients with epilepsy.     

Hippocampal neuronal density in temporal lobe epilepsy with and without gliomas

Summary The majority of patients with temporal lobe epilepsy show hippocampal sclerosis, which pathologically represents neuronal loss and gliosis. We studied volumetric neuronal density on a representative mid to mid-posterior level slice of hippocampi surgically removed from intractable temporal lobe epilepsy cases, and compared the results between 25 non-tumor epilepsy (NTE) cases and 5 tumor-associated epilepsy (TAE) cases. Eleven age-matched non-epileptic autopsy cases were studied as controls. Cells were counted in the CA1 through CA4 fields and the stratum granulosum of the dentate fascia. In NTE every hippocampal field showed statistically significant loss of neurons, the neuronal density in each field ranging from 35% to 50% of that of control. The mean neuronal density between the TAE and NTE groups also showed statistically significant differences in all hippocampal fields. The neuronal density of hippocampal fields of NTE ranged from 43% to 58% of that of TAE. Tumor-associated epilepsy cases, however, failed to show any statistically significant deviation from the control in their neuronal density. The etiology of the difference in neuronal density between the TAE and NTE groups is discussed.Supported by NIH grant NS06208     

Hippocampal synaptic pathology in patients with temporal lobe epilepsy

Immunostaining of synaptic terminals was studied in the hippocampus of 26 patients who had surgical resections for intractable temporal lobe epilepsy. Two monoclonal antibodies (EP10 and SP12) reactive with distinct synaptic antigens were used on paraffinembedded tissues. The results indicated qualitative reductions on synaptic terminals in CA4 and other regions where cell loss is reported. The inner molecular layer of the dentate gyrus was observed to have increased synaptic immunostaining. Synaptic terminal loss in CA4 and redistribution in the molecular layer were most frequent in cases with hippocampal sclerosis. However, both forms of synaptic pathology were also noted in most cases where the pathological findings were classified as indefinite, and in some cases associated with mass lesions of the temporal lobe. These results support the importance of neuronal loss and synaptic reorganization as possible mechanisms of illness in epilepsy. They also indicate that synaptic immunostaining may be a useful adjunct to routine neuropathological diagnostic techniques.Supported by the British Columbia Health Research Foundation and the Theodore and Vada Stanley Foundation     

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.     

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.     

不同手术入路治疗海马硬化性颞叶内侧癫痫的比较

目的 比较常用的四种手术方式在治疗海马硬化性颞叶内侧癫痫(MTLE/HS)中的优缺点.方法 106例顽固性MTLE/HS患者中23例行经皮层脑室入路选择性海马杏仁核切除术;23例行经侧裂选择性海马杏仁核切除术;30例行前内侧颞叶切除术;30例行经颞下选择性海马杏仁核切除术.随访6个月-9年.采用Engel分级量表评价癫痫治疗效果,并比较并发症发生率.结果 四种术式在对癫痫发作的治疗效果比较上差异无统计学意义,无手术死亡,在并发症发生率方面差异无统计学意义.结论 对于经严格筛选的MTLE/HS,四种手术方式在疗效和安全性方面相当,可根据个人手术经验加以选择.     

Hippocampal formation involvement in a language-activation task in patients with mesial temporal lobe epilepsy

PURPOSE: The study aims to explore the contribution of the hippocampal formation to the retained language-comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE). METHODS: We performed a functional magnetic resonance (MRI) study based on a language comprehension paradigm in 45 right-handed patients with unilateral mesial TLE and 35 healthy control subjects. Activations in the hippocampal formations in both hemispheres were analyzed for each subject as well as for groups of left TLE, right TLE, and controls. RESULTS: In sum, 82% of TLE patients displayed hippocampal activations. A significant difference in hippocampal activation between left and right TLE was found: Right TLE patients showed increased activity in the left hippocampal formation compared with left TLE patients. In contrast, patients with left TLE did not show increased activity in the right hippocampal formation compared with right TLE patients. In comparison with a healthy control group, right TLE patients activated the left hippocampal formation to a greater extent, whereas patients with left TLE did not activate the right hippocampal formation to a greater degree. These findings point to an increased involvement of the left hippocampal formation during a language-comprehension task in right TLE patients. In contrast, left TLE in right-handed patients seems not associated with an enhanced involvement of the right hippocampal formation in retained language comprehension. CONCLUSIONS: These findings suggest that effective language comprehension in right-handed subjects with TLE depends on the involvement of the left hippocampal formation and underline the risks of postoperative language decline in patients with left TLE.     

Thalamo-cortical network dysfunction in temporal lobe epilepsy

ObjectivesImaging and neurophysiological data shows that the cortical disfunction caused by focal epilepsy is not limited to the epileptic focus, thus raising the modern vision of focal epilepsy as a network disorder. The involvement of deep thalamo-cortical projections in temporal lobe epilepsy is a clear example. We aimed at demonstrating the interictal functional impairment of thalamo-cortical network in drug-naïve TLE patients through the study of high frequency oscillations of somatosensory evoked potentials (HF-SEP).MethodsTwelve healthy controls (HC; 8 females, 52.2 ± 17.3 years-old) and 12 drug-naïve TLE patients (8 females, 55.5 ± 21.5 years-old) underwent bilateral median HF-SEP, recorded by scalp electrodes. Cp3′-Fz and Cp4′-Fz traces were filtered (400–800 Hz) to evidence HF-SEP.ResultsHF-SEP duration in the affected hemisphere was significantly longer when compared to that of both the unaffected hemisphere and HC hemispheres. No significant inter-hemispheric differences were found in areas, powers and latencies of HF-SEP wavelets.ConclusionOur results demonstrate that TLE induces early interictal functional impairments of the thalamo-cortical network.SignificanceOur data strongly corroborates the vision of focal epilepsy as a network disorder and offers a new neurophysiological tool to test pharmacological, surgical and neuromodulatory therapies.     

Spatial localization and time-dependant changes of electrographic high frequency oscillations in human temporal lobe epilepsy

Purpose:   High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity.
Methods:   Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained from seven patients with temporal lobe epilepsy using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC-500 Hz. We examined the spatial distribution of the different spectral bands 5 s before and 5 s after seizure onset. Temporal changes in the spectral bands were studied in the 30-s period leading up to seizure onset.
Results:   Three main observations were made. First, HFOs (100–500 Hz) can be recorded using commercial depth and subdural grid electrodes. Second, HFOs, but not <100 Hz oscillations, were localized to channels of ictal onset (100–200, 400–500 Hz, p < 0.05; 300–400 Hz, p < 0.001). Third, temporal analysis showed increased HFO power for approximately 8 s prior to electrographic onset (p < 0.05).
Conclusions:   These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.     

Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy

It has been hypothesized on the basis of animal models of epilepsy that abnormal neural activity in epilepsy may be related to reorganized neural circuits that facilitate epileptogenesis. Little evidence of this was available for human epilepsy. This paper provides the first evidence of such reorganization of a hippocampal seizure focus in human temporal lobe epilepsy (TLE). This reorganization involves the selective loss of somatostatin and neuropeptide Y immunoreactive interneurons, and axonal sprouting of other neuropeptide Y neurons and dynorphin-A immunoreactive granule cells. This set of changes is not exactly like those that are reported in animal models.     

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。     

Volumetric evidence of bilateral damage in unilateral mesial temporal lobe epilepsy

PURPOSE: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for >or=4 years of postsurgical follow-up. METHODS: Forty-six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow-up of >or=4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness. RESULTS: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls. CONCLUSIONS: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE.     

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.     

海马硬化与颞叶癫痫术前定位探讨(附12例报告)

目的　探讨对顽固性颞叶癫痫的术前定位方法。方法　将 Ｍ Ｒ 对海马硬化的诊断作为一重要参考指标与 Ｅ Ｅ Ｇ 检查相结合,对１２ 例顽固性颞叶癫痫进行术前定位诊断,并与术中皮层 Ｅ Ｅ Ｇ 检查结果和术后随访结果比较。结果　 Ｍ Ｒ 检查发现９ 例海马硬化,皮层 Ｅ Ｅ Ｇ 证实有同侧颞叶内侧放电,行选择性海马杏仁核切除术后病理证实海马硬化;未发现海马硬化改变３ 例行前颞叶切除术。随访０５ ～２ 年,疗效满意。结论　 Ｅ Ｅ Ｇ 是诊断颞叶癫痫的最重要手段, Ｍ Ｒ 发现海马硬化对致痫灶定位有重要意义。     

神经导航下锁孔入路选择性海马杏仁核切除术治疗内侧颞叶癫痫

目的 探讨神经导航下锁孔入路选择性海马杏仁核切除术治疗顽固性内侧颞叶癫痫的可行性.方法 总结分析18例神经导航下锁孔入路选择性海马杏仁核切除病例,所有病例均经过临床特征、影像检查、视频脑电监测、脑磁图检查确定为顽固性内侧颞叶癫痫.结果 随访结果显示72.2%病例术后癫痫发作停止.Engel癫痫疗效分级:Ⅰ级72.2%,Ⅱ级22.2%,Ⅲ级5.6%.结论 神经导航下锁孔入路选择性海马杏仁核切除术是一种安全可行的手术方法,疗效满意.     

Temporal lobe volumetric cell densities in temporal lobe epilepsy

Volumetric cell densities in 13 different subfields of the temporal lobe were calculated to test various hypotheses about mesial and lateral temporal lobe sclerosis in patients with complex partial epilepsy. In patients benefitting (primary group) from anterior temporal lobectomy (ATL), sclerosis was greater (fewer cells) in anterior than in posterior hippocampus. By contrast, the patients lacking full benefit (nonprimary group) from ATL had decreased numbers of neurons equally distributed from anterior to posterior hippocampus, indicating that zones of mesial temporal cell loss are linked to zones of epileptogenicity. These data support a model of focal hippocampal epilepsy originating from zones of cell loss and synaptic reorganization that is epileptic. There were no differences in cell densities in gyrus hippocampi or in lateral temporal gyri when patients with temporal lobe epilepsy and controls were compared. Hippocampal cell densities in mesial temporal lobe were not reduced in psychomotor epileptic patients with extrahippocampal foci consisting of foreign tissue. Variables in seizure histories were not correlated with Ammon's horn cell densities, indicating that most of the sclerosis preceded the seizures, which did virtually no significant further damage to hippocampus with repeated partial or generalized seizures.     

Frequency of bitemporal independent interictal epileptiform discharges in temporal lobe epilepsy

PURPOSE: Bitemporal interictal epileptiform discharges (IEDs) occur in < or =42% of scalp EEGs in patients with temporal lobe epilepsy (TLE) studied with routine EEGs or partial analysis of long-term recordings. METHODS: Twenty-eight patients with TLE demonstrating exclusively unilateral temporal IEDs on routine EEGs underwent 24-h continuous recording. The entire record was visually inspected for epileptiform discharges. We used continuous EEG to assess the significance of long-term recording in detecting bilateral IEDs. RESULTS: Twenty-two patients had left temporal IEDs; 21 had right temporal IEDs. Seventeen (61%) patients had IEDs originating from both the right and left temporal lobes. The probability of detecting bilateral independent IEDs was correlated with the duration of continuous EEG recording. There was no correlation between the number of IEDs originating from one side and the probability of detecting independent IEDs on the other side. The frequencies of IEDs were not correlated with the length of time since onset of epilepsy. CONCLUSIONS: The findings suggest that when long-term recordings are performed, the incidence of bilateral discharges in TLE is higher than previously reported in the literature and supports the view that TLE is commonly a bilateral disease.     

Correlation between 1H MRS and memory before and after surgery in mesial temporal lobe epilepsy with hippocampal sclerosis

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE-HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two patients underwent memory tests and 1H MRS investigation before and 6 months after SAH and were compared with nine control subjects. RESULTS: The 1H MRS scores were found to be significantly low on the pathological side of the patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of left TLE patients were correlated only with verbal memory scores. Statistical analysis did not reveal any significance for nonverbal memory scores for both TLE groups on either side, which showed no significant correlation between material specificity and 1H MRS findings. Conversely, regression analyses demonstrated that high right- and low left-sided 1H MRS values obtained before surgery may predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS can be considered as a useful tool to determine the lateralization in patients with MTLE-HS before the surgery. Although only a weak relation exists between the MRS values and memory scores, presurgical MRS scores may be predictive for a possible deterioration in verbal memory after surgery. However, further studies with higher numbers of cases are needed for confirmation of the results.