TLR9、MyD88在颞叶癫痫大鼠海马组织中表达的动态变化

目的观察氯化锂-匹罗卡品致痫大鼠各期海马中Toll-样受体9(TLR9)、髓样分化因子(MyD88)表达的变化,探讨其是否与颞叶癫痫发生有关。方法 SD雄性大鼠120只,随机分为对照组(30只)和模型组(90只),腹腔注射氯化锂。18 h~20 h后模型组腹腔注射匹罗卡品诱导癫痫持续状态(SE);对照组予等量生理盐水取代匹罗卡品腹腔注射。对照组和造模成功的模型组依据腹腔注射后时间随机分为10个亚组:急性模型组(SE后3 h、6 h、9 h、12 h、1 d、3 d、7 d);潜伏模型组(SE后14 d、28 d);慢自发发作组(SE后56 d)。每亚组动物模型组9只,对照组3只。免疫组化、蛋白印迹、RT-PCR技术测定各亚组癫痫大鼠海马内TLR9、MyD88的表达。结果TLR9、MyD88在模型组海马内表达明显增多,与对照组相比,差异有显著性(P0.05)。模型亚组内,TLR9、MyD88在急性期和慢性期表达明显增高,而潜伏期无明显表达变化。其中急性期内的增高多集中在癫痫发作后6 h;3组比较差异有显著性(P0.05)。结论大鼠海马内TLR9、MyD88表达增多可能与颞叶癫痫发病有关,探讨其机制可能为颞叶癫痫的治疗提供新的靶点。     

Temporal lobe epilepsy in children: etiology in a cohort with new-onset seizures

PURPOSE: The aim of this study was to characterize the incidence and etiology of temporal lobe epilepsy (TLE) in a community-based cohort of children with new-onset disease. METHODS: A community-based cohort of 30 children with TLE was studied. The patients had new-onset disease before age 14 years between 1995 and 1999. They underwent clinical, EEG, and magnetic resonance imaging investigations. RESULTS: The patients could be divided in three main groups according to likely etiology, as suggested by Harvey et al. (Neurology 1997;49:960-8). Group 1 consisted of eight (26.7%) children with malformations or long-standing, nonprogressive tumors (developmental TLE). Arachnoid cysts were found in three, dual pathology [cortical dysplasia and hippocampal sclerosis (HS)] in one, and focal cortical dysplasia with glioproliferative changes in one patient. Dysembryoplastic neuroepithelial tumor was responsible for the epilepsy in one, and ganglioglioma, in two children. Group 2 consisted of seven (23.3%) children with a significant antecedent and/or HS. Five children had a significant illness or event before the onset of TLE, including perinatal hypoxic-ischemic encephalopathy in one, encephalitis in one, traumatic brain injury in two, and complex febrile seizures in one. HS was found in the patients with traumatic brain injury and complex febrile seizures in the history in addition to two children without known antecedents. Group 3 comprised 15 (50%) children with no abnormality on neuroimaging and no significant antecedents (cryptogenic TLE). CONCLUSIONS: Etiologic differences between children with new-onset TLE may have prognostic implications: children with TLE and significant antecedents/HS are expected to have the greatest risk of continued seizures and psychological problems.     

Persistent zinc depletion in the mossy fiber terminals in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy

Purpose:   Zinc is released in synaptic vesicles with glutamate, and modulates glutamatergic neurotransmission. In brain, the highest amount of zinc, detected by Timm staining, is in the mossy fiber (MF) system in the hippocampus. In the intrahippocampal kainate (KA) mouse model of mesial temporal lobe epilepsy, which is elicited by intrahippocampal KA, prominent MF sprouting develops rapidly within 2 weeks post-KA. However, the intensity of Timm staining is reduced gradually thereafter. The present study is designed to determine the mechanisms underlying this reduction of Timm staining.
Methods:   The changes in Timm staining, and VGluT1, Synapsin-1, and zinc transporter 3 (ZnT3) immunoreactivity (IR) were examined from 4–56 days post-KA. An analysis of glutamate release in the KA-injected hippocampus was conducted by microdialysis before and during the continuous injection of midazolam (MDZ).
Results:   At 56 days post-KA, Timm staining disappeared completely, whereas VGluT-1-, Synapsin-1-, and ZnT3-IR were increased in the sprouted MF boutons. However, when the seizures were suppressed by a continuous perfusion of MDZ, the glutamate release in the hippocampus decreased and Timm staining was recovered.
Discussion:   This study showed that the reduction of Timm staining is the result of decreased zinc content but not the loss of MF itself. The reduction is the result of the enhanced release of zinc relative to storage, and it should facilitate the glutamate excitation that might be related to the epileptogenesis and rapid advancement of the morphologic changes in this model.     

Granule cell dispersion develops without neurogenesis and does not fully depend on astroglial cell generation in a mouse model of temporal lobe epilepsy

Purpose: Granule cell dispersion (GCD) appears as a characteristic morphological feature of the mesial temporal lobe epilepsy (MTLE). It has been suggested that this phenomenon could be due to an increased neurogenesis in the dentate gyrus. However, this hypothesis is still debated and recent clinical and experimental studies have shown that neurogenesis is rather decreased in MTLE. To further determine the role of neural and astroglial cell generation in GCD we examined the consequences of aging and irradiation, which are known to reduce progenitor cells, in a mouse model of MTLE induced by intrahippocampal kainate (KA) injection. Methods: We injected KA in hippocampus of three different types of mice; (1) young adult, (2) aged, and (3) irradiated mice. Newly generated cells were labeled by Bromodeoxyuridine (BrdU) and were characterized by immunohistochemistry. The extent of GCD was compared among the three animal groups. Results: In young adult mice, BrdU‐labeled neurons as well as doublecortin‐ and NeuroD‐positive cells decreased progressively after KA injection whereas BrdU‐labeled astrocytes and microglias increased. In aged and irradiated mice, where basal neurogenesis was already strongly reduced, GCD developed after KA injection to the same extent as in young adult mice. However, augmentation of the BrdU‐labeled astrocytes after KA was less than 40% in irradiated mice in comparison to young and aged mice. Conclusions: Our data show that GCD occurs without neurogenesis. Furthermore GCD developed regardless of the degree of astroglial cell proliferation, suggesting that neural stem cell generation is not crucial for GCD.     

Secondarily generalized seizures in temporal lobe epilepsy

Purpose: Secondarily generalized tonic–clonic seizure (SGTCS) may occur rarely in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure‐related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (1) What clinical features differentiate patients with TLE who regularly had SGTCS from those who did not? (2) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data? Methods: We included 171 patients with TLE (mean age 34.4 ± 10) who participated in our presurgical evaluation program, which included continuous video–electroencephalography (EEG) and magnetic resonance imaging (MRI). Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To reevaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we reevaluated only the first three. Altogether video‐recorded seizures of 402 patients were reanalyzed. Key Findings: A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, whereas ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive association, whereas patient’s reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal‐onset seizure during video‐EEG monitoring. Significance: Clinical features associated with SGTCS may help clinicians during presurgical monitoring identify high‐risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.     

匹罗卡品致痫小鼠自发性癫痫发作模型的建立及癫痫后海马新生神经细胞增生的研究

目的探讨匹罗卡品致痫小鼠自发性癫痫发作(SS)模型的特点,并观察癫痫发作后其齿状回颗粒细胞下层新生神经细胞(NPC)增生变化。方法建立SS小鼠模型,进行行为学检测。将SS发作小鼠在癫痫持续状态(SE)后不同时间点进行Doublecortin(DCX)免疫组化,Western blot观察海马NPC的分布和表达改变。结果 80%的模型小鼠出现持续SS,发作时程约10～40 s,发作频率为2.18±0.45次/周。DCX+细胞及其蛋白表达在模型组中显著增多(P<0.05),SE后4周最为明显,SE后8周开始下降,至SE后12周显著减少。增生的DCX+细胞呈簇状分布,随时间推移出现迁移分散。存在SS的模型小鼠相对于不存在SS的模型小鼠DCX+细胞增生更为明显。结论匹罗卡品致痫后SS小鼠模型存在持续的NPC增生,这可能在慢性期癫痫持续发作的病理生理机制中有着重要作用。     

MRI影像改变对颞叶癫痫术后疗效的影响

目的 研究颞叶癫痫(TLE)患者的MRI影像与病理结果 的相关性,分析不同MRI改变对术后疗效的影响.方法 回顾2005年1月至2008年12月在我科手术治疗且有效随访的121例TLE患者的临床资料,统计分析MRI影像改变与病理结果 的关系;根据MRI影像改变将患者分为内侧型TLE、有结构性改变的TLE和隐源性TLE,利用Engel分级将患者分为无发作组和发作组,比较不同类型TLE患者术后疗效的差异.结果 121例患者中MRI结果 阳性101例,病理结果 阳性107例,二者差异无统计学意义,具有良好的相关性.隐源性TLE患者的术后疗效较内侧型TLE和有结构性病变的TLE差,而后二者之间差异无统计学意义.结论 MRI检查对于TLE的确诊及预后判断具有重要意义.     

Prognostic implication of contralateral secondary electrographic seizures in temporal lobe epilepsy

PURPOSE: Interhemispheric propagation of seizures in temporal lobe epilepsy is frequently noted during intracranial EEG monitoring. We hypothesized that a distinct secondary electrographic seizure (DSES) in the temporal lobe contralateral to primary seizure onset may be an unfavorable prognostic indicator. METHODS: We reviewed intracranial depth electrode EEG recordings, 1-year outcome, and medical records of 51 patients (M 29, F 22: age 15-64 years) who underwent anterior temporal lobectomy during 1988-96. We defined DSES as a seizure that spread to the contralateral temporal lobe and produced distinct contralateral EEG features. The distinct feature was focal involvement of one or two electrode contacts at onset, which starts and evolves independently from the ipsilateral temporal lobe. We considered DSES as the predominant seizure pattern when it occurred in more than one half of the patients' recorded seizures. RESULTS: Only nine of 19 (47%) patients with predominant DSES had a 1-year seizure-free outcome, whereas 27 of 32 (84%) patients without predominant DSES had a 1-year seizure-free outcome (p < 0.01). Bitemporal independent seizures were more common in patients with predominant DSES (9/19 versus 0/32; p < 0.001). CONCLUSION: Our results suggest that distinct contralateral secondary electrographic seizure is a predictor of unfavorable outcome and is also more likely to be associated with bitemporal seizures.     

Effects of fluoxetine and TFMPP on spontaneous seizures in rats with pilocarpine-induced epilepsy

PURPOSE: Fluoxetine is a selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitor (SSRI) commonly used to treat depression. Some uncontrolled clinical studies have reported that SSRIs increase seizures, but animal experiments with evoked-seizure models have suggested that SSRIs at therapeutic doses decrease seizure susceptibility. We tested the hypothesis that fluoxetine and trifluoromethylphenylpiperazine (TFMPP, a nonselective 5-HT-receptor agonist) reduce the frequency of spontaneous motor seizures in pilocarpine-treated rats. METHODS: Fluoxetine (20 mg/kg) and TFMPP (5 mg/kg) were administered to rats with pilocarpine-induced epilepsy. Phenobarbital (PB; 10 mg/kg) was a positive control, and saline (i.e., 0.5 ml) controlled for the injection protocol. Each rat received each treatment (intraperitoneally) once per day for 5 consecutive days with 1 week between treatments. Rats were continuously video-monitored for the last 72 h of each treatment. RESULTS: When compared with saline over the entire 72-h observation period, PB and fluoxetine treatment, but not TFMPP, reduced the spontaneous-seizure rate. Plots of magnitude of the drug effect as a function of seizure frequency after saline treatment revealed larger drug effects for fluoxetine and PB in the rats with the highest control seizure rate. When the data from the five rats with the highest seizure frequency in saline were analyzed for the first 6 h after treatment, TFMPP also significantly reduced seizure frequency. CONCLUSIONS: Animal models with spontaneous seizures can be used to screen potential antiepileptic drugs, and fluoxetine and TFMPP reduce spontaneous seizures in the pilocarpine model of temporal lobe epilepsy.     

Hyperkinetic seizures in patients with temporal lobe epilepsy: clinical features and outcome after temporal lobe resection

Purpose: Temporal lobe epilepsy (TLE) is usually associated with automatisms. Hyperkinetic seizures are supposed to be unusual. Because we witnessed several patients with TLE and ictal hyperkinetic symptoms, we retrospectively assessed the number, clinical findings, and seizure outcome in such patients who had undergone temporal lobe resection. Methods: We reviewed medical history, video–electroencephalography (EEG) recording and neuroimaging of adult patients who underwent epilepsy surgery for TLE at the Kork Epilepsy Center over the last 20 years with a minimum postoperative follow‐up of 12 months. Key Findings: Among 294 patients who were resected exclusively in the temporal region, we identified 17 (6%) who presented with hyperkinetic semiology such as violent vocalization, complex movements of the proximal segments of the limbs, rotation of the trunk, pelvic thrusting, or early tonic or dystonic posturing. Most of the patients had a preceding aura. Ictal EEG activity was located in the corresponding temporal region, usually with a wide distribution over temporal electrodes with fast spread to unilateral frontal electrodes and to the contralateral side. Neuroimaging revealed extended lesions in the temporal lobe involving mesial and neocortical structures. Most of the patients underwent classical anterior temporal lobe resection including amygdalo‐hippocampectomy. Fourteen patients (82%) became completely seizure‐free (Engel class Ia). Histopathology showed mainly focal cortical dysplasia plus hippocampal sclerosis. Significance: Hyperkinetic seizure semiology may occasionally occur in patients with TLE and is, therefore, no contradiction to the hypothesis of TLE if scalp EEG patterns and neuroimaging findings correspond. The postoperative seizure outcome is favorable in such patients and not different from outcome data in classical TLE.     

Clinical value and predictors of subclinical seizures in patients with temporal lobe epilepsy undergoing scalp video-EEG monitoring

The aim of this study was to determine the clinical importance and predictors of SCSs in a large population of patients with temporal epilepsy (TLE) undergoing video electroencephalographic (VEEG) monitoring. We reviewed the VEEG data of 327 consecutive patients with TLE admitted to our epilepsy center between August 2012 and January 2017. Demographic, electro-clinical, and neuroimaging data were recorded and re-analyzed. To our knowledge, this is the first study assessing SCSs recorded by long-term VEEG monitoring in patients with TLE. Twenty-seven of 327 (8.3%) patients exhibited SCSs during VEEG monitoring. Of these patients, 24 had both SCSs and clinical seizures. The mean duration of the SCSs was 23.18 s (range: 5–1307 s). Of the 27 patients with SCSs, 24 (88.9%) showed localizing value during the diagnostic process. Seventeen patients exhibited colocalization with clinical seizures, 4 showed useless localization related to clinical seizures, and 3 did not have clinical seizures. Sixteen patients (59.3%) experienced their first SCSs within the first 24 h of monitoring and one had the first SCSs within 20 min. Multivariate logistic regression analysis showed that age <18 years at VEEG monitoring (OR = 3.272, 95% CI = 1.283–8.343, p = 0.013) and bilateral IEDs (OR = 4.558, 95% CI = 1.982–10.477, p < 0.001) were independently associated with the presence of SCSs. Thus, SCSs are not uncommon in patients with TLE, particularly those with age <18 years or bilateral IEDs, and should be considered of significant clinical relevance during the diagnostic process.     

难治性颞叶癫痫术后急性发作对远期预后的预测价值

目的探讨药物难治性颞叶癫痫术后急性发作对远期预后的影响。方法回顾性分析我院自2009年6月-2010年6月收治的52例药物难治性颞叶癫痫患者的临床资料,所有患者均接受外科治疗,术后定期门诊或电话随访。根据术后7天患者有无急性发作,分为2组,分为实验组(复发),对照组(未复发)。将2组患者随访资料、远期预后(5年)等进行对比分析。结果实验组癫痫控制满意率为35.0%,对照组控制满意率为68.8%,实验组明显低于对照组,差异有统计学意义(χ2=5.683,P=0.017)。在多元Logistic回归分析结果中,复发次数、术前使用抗癫痫药物数量、术后脑电图,术后急性发作与术前习惯性发作相似是影响远期预后的独立影响因子。结论难治性颞叶癫痫术后急性发作对患者远期预后存在影响,已明确的影响因子包括:复发次数、术前抗癫痫药≥3种,术后脑电图及术后急性发作与术前习惯性发作相似。     

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.     

Mitochondrial involvement in temporal lobe epilepsy

Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca²⁺ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

颞叶癫(癎)影像诊断和脑电图分析

目的探讨CT和脑电图(EEG)对颞叶癫的诊断作用。方法分析使用美国GE1800型CT机及ND-82B型EEG仪监测的28例颞叶癫。结果CT检查正常6例(21.4%),异常22例(78.6%)。EEG记录间歇期样发作19例,临床发作期9例。结论CT结合EEG对颞叶癫的诊断、定位具有重要意义。     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

成人颞叶癫痫发作间期CT灌注成像的变化

目的探讨成人颞叶癫痫发作间期单侧和双侧痫性放电CT灌注成像的变化。方法将21例颞叶癫痫患者根据视频脑电图监测分为单侧痫性放电组11例、双侧痫性放电组10例,两组患者均在发作间期行CT灌注成像检查,计算每例患者双侧颞叶脑血流量(cerebral blood flow,CBF)、脑血容量(cerebral blood volume,CBV)、平均通过时间(mean transit ti me,MTT)的灌注参数,并比较每组患者颞叶CBF、CBV、MTT以及两组的CBF、CBV、MTT不对称指数(asymmetry index,AI)。结果21例患者头颅CT平扫均无异常,每组患者发作间期双侧颞叶CBF、CBV、MTT差异无统计学意义(P>0.05),两组患者CBF不对称指数差异有统计学意义(t=2.269,P=0.035),CBV和MTT不对称指数差异无统计学意义(P>0.05),在单侧痫性放电组中,痫性放电侧颞叶脑血流量较对侧有所减低,但比较差异无统计学意义(t=-2.093,P=0.063)。结论颞叶癫痫CT灌注成像显示颞叶区发作间期单侧痫性放电较双侧痫性放电脑血流量不对称。     

Long-term seizure outcome and its predictors in patients with recurrent seizures during the first year aftertemporal lobe resective epilepsy surgery

Purpose: The existing data on the implications of the characteristics of seizures that recur during the first year following epilepsy surgery on subsequent seizure outcome are conflicting. We investigated the impact of recurrent seizures in the first postoperative year and their attributes on long‐term seizure outcome. Methods: We studied the postoperative courses of 492 patients who had completed two or more years of follow‐up after temporal lobe resective epilepsy surgery. We used Kaplan‐Meier survival curves to define long‐term seizure outcome and assessed the predictive value of recurrent seizure characteristics on the outcome by univariate and multivariate proportional hazards regression models. Key Findings: In our patients, seizure recurrences during the first postoperative year, irrespective of the attributes of recurrent seizures (such as provoked vs. unprovoked, and timing and number of recurrences), imparted fourfold to sevenfold increased hazards for continued seizures beyond the first postoperative year. Although patients with complex partial seizures with or without secondary generalized tonic–clonic seizures (CPS/GTCS) had a sixfold increased risk, those with auras alone had only a borderline risk for seizures beyond the first postoperative year. In the multivariate model, CPS/GTCS as the predominant seizure type and three or more seizure recurrences during the first postoperative year independently predicted unfavorable long‐term seizure outcome. Significance: Our study provides valuable information that is helpful in prognosticating and counseling patients, and in making rational decisions on the withdrawal of antiepileptic drugs following surgery. Our findings enhance the general understanding of the etiopathogenesis of surgical failure.     

Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy

The hippocampus of patients with mesial temporal lobe epilepsy is often hardened and shrunken, a condition known as sclerosis. Magnetic resonance imaging reveals an increase in the T2-weighted signal, while diffusion weighted imaging shows a higher apparent diffusion coefficient in sclerotic hippocampi, indicating increased water content. As water transport appears to be coupled to K⁺ clearance and neuronal excitability [4], the molecular basis of the perturbed water homeostasis in the sclerotic hippocampus was explored. The expression of aquaporin-4 (AQP-4), the predominant water channel in the brain, was studied with quantitative real time PCR analysis, light microscopic immunohistochemistry and high-resolution immunogold labeling. A significant increase in AQP-4 was observed in sclerotic, but not in non-sclerotic, hippocampi obtained from patients with medically intractable temporal lobe epilepsy. This increase was positively correlated with an increase in the astrocyte marker glial fibrillary acidic protein. AQP-4 was localized to the plasma membranes of astrocytes including the perivascular end-feet. Gene expression associated with increased AQP-4 was evaluated by high throughput gene expression analysis using Affymetrix GeneChip U133A and related gene networks were investigated with Ingenuity Pathways Analysis. AQP-4 expression was associated with a decrease in expression of the dystrophin gene, a protein implicated in the anchoring of AQP-4 in perivascular endfeet. The decreased expression of dystrophin may indicate a loss of polarity in the distribution of AQP-4 in astrocytes. We conclude that the perturbed expression of AQP-4 and dystrophin may be one factor underlying the loss of ion and water homeostasis in the sclerotic hippocampus and hypothesize that the reported changes may contribute to the epileptogenic properties of the sclerotic tissue.The first two authors contributed equally to this study.