Efficacy of hippocampal transection for left temporal lobe epilepsy without hippocampal atrophy

We describe a case of left temporal lobe epilepsy without hippocampal atrophy. A 31-year-old woman presented with typical symptoms of complex partial seizures. Magnetic resonance imaging demonstrated slightly obscure internal structures in the left hippocampus. Scalp electroencephalography revealed interictal epileptiform discharges in the left temporal lobe. A Wada test with propofol determined the language-dominant hemisphere to be the left. Intraoperative electrocorticography revealed active epileptic discharges in the hippocampus and the anterior temporal basal area. The hippocampal epileptic area was treated with multiple transection, which led to the complete cessation of epileptic discharges. After surgery, the Rey Auditory Verbal Learning Test score decreased from 12 to 9. However, it returned to the preoperative level 6months after surgery. We describe this case as a typical example demonstrating the efficacy of hippocampal transection for seizure control and the preservation of verbal memory.     

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.     

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。     

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。     

Corpora amylacea replace the hippocampal pyramidal cell layer in a patient with temporal lobe epilepsy

A 39-year-old woman, with a 23-year history of medically intractable seizures of the complex partial type, underwent a left anterior temporal lobectomy and hippocampectomy. Histologic examinations revealed a massive occurrence of corpora amylacea, neuronal loss, and gliosis in the pyramidal cell layer of the hippocampus. The distribution of corpora amylacea in this case was quite distinctive and unlike the patterns of "nonspecific" corpora amylacea formation seen in aging or other neurodegenerative conditions. The pathogenetic aspects of the accumulation of these peculiar bodies are discussed in relation to hippocampal sclerosis.     

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.     

Clinical-electroencephalogram patterns at seizure onset in patients with hippocampal sclerosis

OBJECTIVE: The purpose of this study is to identify specific clinical-electroencephalogram (EEG) patterns at seizure onset in patients with hippocampal sclerosis (HS). METHODS: Sixty-six ictal video-EEG recordings corresponding to 26 patients with HS have been reviewed, focusing on the EEG features found during the first 30 ictal s. The EEG activity has been classified into the following groups: (A) according to spatial distribution: type 1: temporal electrodes on one side; type 2: temporal and adjacent frontal electrodes on one side; and type 3: non-lateralizing electrographic activity; and (B) according to morphology; subtype (a): regular 5-9 Hz rhythmic activity (RA); subtype (b): low-voltage rapid activity, followed by a 5-9 Hz RA; and subtype (c): irregular EEG sharp waves.We analyzed the clinical symptoms sequence and established the relationship with the ictal EEG patterns. RESULTS: Considering spatial distribution and morphology, the most frequent ictal EEG patterns were type 1 (57%), type 2 (37%), and subtype (a): 62%; subtype (b): 27%; and subtype (c): 11%. The sequence of clinical symptoms observed was: aura-->behavioral arrest-->oro-alimentary automatisms-->unilateral hand automatisms. All seizures with aura and including two or more symptoms of the clinical sequence (65%) were associated with a 1a, 1b, 2a or 2b EEG pattern. CONCLUSIONS: The identification of a specific clinical-EEG pattern provides a useful tool for the epileptogenic zone localization in non-invasive pre-surgical assessment of patients with hippocampal sclerosis. SIGNIFICANCE: The identification of a specific clinical-EEG pattern associated to neuroimaging findings and neuropsychological testing allows indicating surgery for the treatment of epilepsy in patients with hippocampal sclerosis, without performing any further complementary studies.     

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy

ObjectiveTo study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE).MethodsWe used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi.ResultsConnectivity analysis revealed significant differences between left and right TLE compared to healthy controls. Left TLE showed widespread impairment of task-positive language networks, while right TLE showed less pronounced alterations. Particularly right TLE showed altered connectivity for cortical regions that were part of the default mode network (DMN). Left TLE showed a disturbed functional dissociation pattern along the left hippocampus to left and right inferior frontal language regions, while left and right TLE revealed an altered dissociation pattern along the right hippocampus to regions associated with the DMN.ConclusionsOur results showed an impaired hippocampal integration into active language and the default mode networks, which both may contribute to language impairment in TLE.SignificanceOur results emphasize the direct role of the left hippocampus in language processing, and the potential role of the right hippocampus as a modulator between DMN and task-positive networks.     

Synaptophysin immunoreactivity in temporal lobe epilepsy-associated hippocampal sclerosis

We have previously devised a semiquantitative grading system for hippocampal sclerosis (HS) in specimens resected for intractable temporal lobe epilepsy. The grades range from zero to four based on the amount and distribution of neuronal loss and gliosis. In the present study hippocampal sections from 25 patients who had temporal lobe epilepsy and had previously been assigned a grade were examined with synaptophysin immunohistochemistry, and the synaptic content in specific hippocampal fields was correlated with the results of the HS grading system. There was evidence of both significant synaptic loss and increased synaptic density in different fields of the hippocampus with increasing HS. A marked decrement of synaptic immunostaining was present in fields CA1 and CA4 that were highly correlated with HS grade. Sector CA4 seemed to respond in a more graded or continuous way to the pathological insults occurring in temporal lobe epilepsy than did CA1, which appeared to exhibit an all or nothing response. Also, while the width of the outer part of the molecular layer of the dentate (mld) gyrus decreased with increasing HS grade, the inner part of the mld became wider and showed an increased synaptic density so that the overall width of the mld was increased in the high-grade group. We conclude that quantitative measurement of synaptic loss in CA1 and CA4 using synaptophysin immunohistochemistry is a sensitive method for detecting HS and correlates well with the empirically derived HS grading scale, with CA4 exhibiting a more graded response than CA1. In addition, a plasticity response in the inner part of the mld in patients with high-grade HS has been confirmed and quantitated. Received: 8 September 1998 / Revised, accepted: 21 October 1998     

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.     

Neocortical temporal FDG-PET hypometabolism correlates with temporal lobe atrophy in hippocampal sclerosis associated with microscopic cortical dysplasia

PURPOSE: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. METHODS: Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. RESULTS: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. CONCLUSIONS: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD.     

Unilateral hippocampal sclerosis with contralateral temporal scalp ictal onset

PURPOSE: To investigate the clinical characteristics and surgical outcomes in patients with unilateral hippocampal sclerosis whose scalp ictal EEG recordings localize to the opposite temporal lobe. METHODS: We retrospectively reviewed the data of all adult patients who had undergone depth electrode implantation for suspected temporal lobe epilepsy (TLE) at UCLA (1993-2000) or the Montreal Neurological Institute (1991-1998) to identify patients who had (a) unilateral hippocampal atrophy, and (b) surface ictal recordings in which the majority of seizures appeared to initiate in the opposite temporal lobe, with few or none that were concordant with the hippocampal atrophy. RESULTS: Of 109 patients with suspected TLE who underwent depth electrode study at the two centers, five patients met the aforementioned criteria. Four of these five had very severe hippocampal atrophy, whereas the fifth had mild atrophy but extensive signal change on magnetic resonance imaging (MRI). Depth electrode recordings in four of the five patients yielded clear ictal onset in the mesial temporal lobe ipsilateral to the imaging abnormality (contralateral to apparent scalp ictal onset). One patient had an unusual bitemporal onset pattern, which was nonetheless suggestive of onset in the sclerotic hippocampus. No patient had intracranial ictal onset contralateral to the imaging abnormality. All patients underwent resection of the structurally abnormal temporal lobe. After follow-up of > or = 2 years, four (80%) of five patients were seizure free, while the fifth showed lesser improvement (class III). CONCLUSIONS: Some patients with severe hippocampal sclerosis (sometimes called a "burned-out hippocampus") have atypical spread of ictal discharges, resulting in apparent gross discordance between imaging and scalp ictal recordings. These patients nonetheless have excellent surgical outcomes on the whole. Whether such patients may forego intracranial recordings requires further study.     

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     

颞叶癫痫颅内EEG记录定位与海马病理变化的关系

目的探讨颞叶癫痫颅内EEG记录与颞叶海马病变程度的关系。方法视频EEG证实为颞叶癫痫并经MRI检查的病人序贯进入本研究,采用硬膜下电极及深部电极联合纪录,确定领先发作释放(initialictaldischarge,IID)部位。37例病人中,无或轻度海马萎缩(hippocampalatrophy,HA阴性组)27例,中至中度HA(HA阳性组)者10例。海马病理变化依据MRI检查的海马容积测量及术后组织病理学的海马硬化分级。结果本组HA阴性组27例病人中,9例病人IID广泛出现在海马区、内侧旧皮层及外侧新皮层;3例在海马区及内侧古皮层;14例完全出现在海马区以外的颞叶皮层;仅1例局限于海马区。在HA阳性组中,90%的病人IID局限于海马区(P<0.05),在25例低级别海马硬化(HS)中,IID局限于海马区显著低于12例HS高级别病人(P<0.05)。结论颞叶癫痫的抽搐发作放电定位与海马的病理变化存在着密切关系,无HA和低级别HS病人的IID多出现在海马、颞叶内侧皮层、颞叶新皮层的部位,而HA明显者和高级别的HS病人出现的IID往往仅局限于海马(HF)。     

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.     

Verbal retention lateralizes patients with unilateral temporal lobe epilepsy and bilateral hippocampal atrophy

PURPOSE: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy. METHODS: The sample consisted of 74 patients with EEG-defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using chi2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery. RESULTS: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery. CONCLUSIONS: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI.     

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。     

Quantitative neuropathology of the entorhinal cortex region in patients with hippocampal sclerosis and temporal lobe epilepsy

PURPOSE: Clinical, radiologic, and experimental evidence indicates that the entorhinal cortex (EC) region may be linked to the pathophysiology of hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. Few neuropathologic studies of this region have been undertaken in patients with HS undergoing surgery, some suggesting preferential loss of layer III neurones. METHODS: We carried out a quantitative analysis in 26 patients with HS, nine patients with lesional temporal lobe epilepsy (LTLE), and eight postmortem controls. We measured neuronal densities in EC by using a three-dimensional cell-counting technique on NeuN immunostained and Nissl-stained sections. We also quantified the density of calretinin-positive interneurones in this region and the density of neurones in adjacent subiculum and CA1 subfields. We also assessed the patterns of gliosis in the EC in the patient groups and the presence of any neocortical neurone loss. RESULTS: No significant difference was found in the mean neuronal densities in the EC region between HS and LTLE groups or postmortem controls. Laminar gliosis in midcortical layers was seen in a proportion of HS cases but also in the LTLE group. No significant difference was seen in the density of calretinin interneurones and no correlation between the presence of neocortical neuronal loss and EC neuronal densities. CONCLUSIONS: A stereotypical pattern of neuronal loss and gliosis in the EC region in patients with HS is not confirmed that distinguishes this pathologic process from that in patients with lesional TLE.