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Mesial Temporal Lobe Epilepsy (mesial + temporal_lobe_epilepsy)

Distribution by Scientific Domains

Medical Sciences	93%
Life Sciences	6%

Selected Abstracts

Prognostic Factors for the Surgery for Mesial Temporal Lobe Epilepsy: Longitudinal Analysis

EPILEPSIA, Issue 8 2005
Sang-Wuk Jeong
Summary:,Purpose: Determining long-term prognostic factors of surgery for mesial temporal lobe epilepsy (MTLE) is important for identifying ideal candidates and predicting the prognosis for individual patients. We tried to identify the prognostic factors of anterior temporal lobectomy (ATL) for MTLE with longitudinal multivariate analysis. Methods: Two hundred twenty-seven patients with MTLE were included in this study. The primary outcome variable was patient status 1,5 years after surgery: seizure free, or not. Clinical characteristics and recent diagnostic modalities were considered as prognostic factors. Univariate and standard multiple logistic-regression analysis for outcome at 1 and 5 years after surgery and the generalized estimation equation (GEE) model for longitudinal multiple logistic regression of the 5-year follow-up period were used. Results: The seizure-free rate at 1 year was 81.1% and decreased to 75.2% at 5 years after surgery. By the univariate or standard multiple logistic-regression analysis, age at surgery or hippocampal sclerosis on magnetic resonance imaging (MRI) ipsilateral to surgery was significant for the postsurgical outcome. However, the longitudinal analysis by the GEE model revealed that younger age at surgery [odds ratio (OR), 0.59; 95% confidence interval (CI), 0.43,0.81], absence of secondarily generalized tonic,clonic seizure (2°GTCS; OR, 0.45; 95% CI, 0.26,0.79), and hippocampal sclerosis on MRI (OR, 2.44; 95% CI, 1.11,5.26) were significant predictors of a good surgical outcome. Conclusions: Age at surgery, presence of 2°GTCS, and hippocampal sclerosis on MRI are independent prognostic factors for ATL in MTLE. These findings suggest that MTLE is a progressive disorder, and surgical outcome is better when early ATL is performed. [source]

Correlation between 1H MRS and Memory before and after Surgery in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

EPILEPSIA, Issue 6 2004
Lütfü Hano
Summary: 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. [source]

Magnetic Resonance Imaging Follow-up of Progressive Hippocampal Changes in a Mouse Model of Mesial Temporal Lobe Epilepsy

EPILEPSIA, Issue 6 2000
Viviane Bouilleret
Summary: 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. [source]

Doublecortin expression in the normal and epileptic adult human brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2008
Y. W. J. Liu
Abstract Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy. [source]

Hippocampal volume assessment in temporal lobe epilepsy: How good is automated segmentation?

EPILEPSIA, Issue 12 2009
Heath R. Pardoe
Summary Purpose:, Quantitative measurement of hippocampal volume using structural magnetic resonance imaging (MRI) is a valuable tool for detection and lateralization of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE). We compare two automated hippocampal volume methodologies and manual hippocampal volumetry to determine which technique is most sensitive for the detection of hippocampal atrophy in mTLE. Methods:, We acquired a three-dimensional (3D) volumetric sequence in 10 patients with left-lateralized mTLE and 10 age-matched controls. Hippocampal volumes were measured manually, and using the software packages Freesurfer and FSL-FIRST. The sensitivities of the techniques were compared by determining the effect size for average volume reduction in patients with mTLE compared to controls. The volumes and spatial overlap of the automated and manual segmentations were also compared. Results:, Significant volume reduction in affected hippocampi in mTLE compared to controls was detected by manual hippocampal volume measurement (p < 0.01, effect size 33.2%), Freesurfer (p < 0.01, effect size 20.8%), and FSL-FIRST (p < 0.01, effect size 13.6%) after correction for brain volume. Freesurfer correlated reasonably (r = 0.74, p << 0.01) with this manual segmentation and FSL-FIRST relatively poorly (r = 0.47, p << 0.01). The spatial overlap between manual and automated segmentation was reduced in affected hippocampi, suggesting the accuracy of automated segmentation is reduced in pathologic brains. Discussion:, Expert manual hippocampal volumetry is more sensitive than both automated methods for the detection of hippocampal atrophy associated with mTLE. In our study Freesurfer was the most sensitive to hippocampal atrophy in mTLE and could be used if expert manual segmentation is not available. [source]

Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS)

EPILEPSIA, Issue 10 2009
Chaturbhuj Rathore
Summary 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. [source]

Spontaneous periictal leaving behavior: A potential lateralizing sign in mesial temporal lobe epilepsy

EPILEPSIA, Issue 6 2009
Liri Jin
Summary Purpose:, Seizure-related spontaneous leaving behavior (LB) is an uncommonly reported phenomenon. The aim of this study was to determine its frequency, clinical significance, and especially its lateralizing value. Methods:, We analyzed retrospectively the spontaneous periictal LB occurring in complex partial seizures (CPS) of 138 patients with medically refractory mesial temporal lobe epilepsy (MTLE) with excellent postoperative seizure outcome and pathologic finding of hippocampal sclerosis. The relation of LB occurring in different phases of CPS to the side of resection was investigated. Results:, The overall frequency of periictal LB was 8.3% of 517 CPS and 25.2% of 123 patients. Among the 12 patients with ictal LB, 9 patients had epileptogenic focus ipsilateral to language dominant side, whereas the remaining 3 had seizure onset in the nondominant side. Conversely, 8 of 11 patients with postictal LB had foci in the nondominant side, and only three patients' seizures originated in the dominant side. Therefore, it was more likely for patients with left MTLE to show ictal LB and for those with right foci to display postictal LB (p = 0.03). Conclusions:, LB may represent a potential lateralizing sign. When LB occurs ictally, it may indicate seizure onset in the dominant temporal lobe, and LB occurring postictally indicates nondominant side seizure onset in patients with MTLE. [source]

Strategies for surgical treatment of epilepsies in developing countries

EPILEPSIA, Issue 3 2008
Ali A. Asadi-Pooya
Summary Epilepsy surgery has been proved to be efficacious, safe and cost-effective in developing countries. However, the success of epilepsy surgery depends on selecting suitable candidates based on the available resources and technologies. Some of the challenges to provide appropriate surgical treatment for epilepsy patients in developing countries include providing human and technological resources and developing realistic presurgical protocols. Detection of ideal candidates for epilepsy surgery is possible for well-trained epileptologists with the help of basic investigative technologies, for example, magnetic resonance imaging (MRI) and electroencephalography (EEG). Patients with potentially epileptogenic, well-circumscribed lesions on MRI and patients with mesial temporal lobe epilepsy (MTLE) are reasonable candidates for surgery. Palliative epilepsy surgeries include corpus callosotomy and other disconnections. These operations are feasible in developing countries with a knowledgeable team consisting of an epileptologist, neurosurgeon and technicians and with using MRI and EEG as basic investigative technologies. [source]

Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsy

EPILEPSIA, Issue 1 2008
Christoph Helmstaedter
Summary Purpose: In the surgical treatment of mesial temporal lobe epilepsy, there is converging evidence that individually tailored or selective approaches have a favorable cognitive outcome compared to standard resections. There is, however, also evidence that due to collateral damage, selective surgery can be less selective than suggested. As part of a prospective transregional research project the present study evaluated the outcome in memory and nonmemory functions, following two selective approaches: a combined temporal pole resection with amygdalohippocampectomy (TPR+) and transsylvian selective amygdalohippocampectomy (SAH). Methods: One year after surgery, cognitive outcomes of postoperatively seizure-free patients with mesial TLE and hippocampal sclerosis, who underwent either TPR+ (N = 35) or SAH (N = 62) in two German epilepsy centers (Bonn/Berlin), were compared. Results: Repeated measurement MANOVA and separate post hoc testing indicated a double dissociation of verbal/figural memory outcome as dependent on side and type of surgery. Verbal memory outcome was worse after left-sided operation, but especially for SAH, whereas figural memory outcome was worse after right-sided operation, preferentially for TPR+. Attention improved independent of side or type of surgery, and language functions showed some improvement after right-sided surgeries. Discussion: The results indicate a differential effect of left/right SAH versus TPR+ on material-specific memory insofar as transsylvian SAH appears to be favorable in right and TPR+ in left MTLE. The different outcomes are discussed in terms of a different surgical affection of the temporal pole and stem, and different roles of these structures for verbal and figural memory. [source]

Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double-Blind, Long-Term Follow-Up Study

EPILEPSIA, Issue 10 2007
Ana Luisa Velasco
Summary:,Purpose: Our aim was to evaluate the safety and efficacy of electrical stimulation of the hippocampus in a long-term follow-up study, as well as its impact on memory performance in the treatment of patients with refractory mesial temporal lobe epilepsy. Methods: Nine patients were included. All had refractory partial complex seizures, some with secondary generalizations. All patients had a 3-month-baseline-seizure count, after which they underwent bilateral hippocampal diagnostic electrode implantation to establish focus laterality and location. Three patients had bilateral, and six, unilateral foci. Diagnostic electrodes were explanted and definitive Medtronic electrodes were implanted directed into the hippocampal foci. Position was confirmed with MRI and afterwards, the deep brain stimulation system internalized. Patients signed the informed consent approved by the Hospital's Ethics Committee and began a double-blind stimulation protocol. Patients attended a medical appointment every 3 months for seizure diary collection, deep brain stimulation system checkup, and neuropsychological testing. Results: Follow-up ranged from 18 months to 7 years. Patients were divided in two groups: five had normal MRIs and seizure reduction of >95%, while four had hippocampal sclerosis and seizure reduction of 50,70%. No patient had neuropsychological deterioration, nor did any patient show side effects. Three patients were explanted after 2 years due to skin erosion in the trajectory of the system. Conclusions: Electrical stimulation of the hippocampus provides a nonlesional method that improves seizure outcome without memory deterioration in patients with hippocampal epileptic foci. [source]

Voxel-based T2 Relaxation Rate Measurements in Temporal Lobe Epilepsy (TLE) with and without Mesial Temporal Sclerosis

EPILEPSIA, Issue 2 2007
Susanne G. Mueller
Summary:,Introduction: Quantitative measurements of T2 relaxation in the hippocampus for focus lateralization in mesial temporal lobe epilepsy (mTLE) are well established. Less is known to what degree such relaxation abnormalities also affect regions beyond the ipsilateral hippocampus. Therefore, the aim of this study was to characterize extent and distribution pattern of extrahippocampal relaxation abnormalities in TLE with (TLE-MTS) and without MRI evidence of mesial-temporal sclerosis (TLE-no). Methods: Double spin echo images (TE1/2: 20/80 ms) acquired in 24 TLE-MTS and 18 TLE-no were used to calculate relaxation rate maps. These maps were analyzed by SPM2 and by selecting regions of interest (ROI) in the hippocampus and several extrahippocampal brain regions. Results: In TLE-MTS, the results of the SPM and ROI analysis were in good agreement and showed the most severe relaxation rate decreases in the ipsilateral hippocampus but also in other ipsilateral temporal regions, orbitofrontal, and parietal regions and to a lesser degree in contralateral frontal regions. The relaxation rate decreases in TLE-no were confined to small regions in the ipsilateral anterior inferior and medial temporal lobe in the SPM analysis while ROI analysis showed additional regions in the ipsilateral hippocampus, amygdala, and anterior cingulate. Conclusion: TLE-MTS showed extensive, widespread but predominantly ipsilateral temporal and also extratemporal T2 relaxation rate decreases. In contrast, the findings of the SPM and ROI analyses in TLE-no suggested that if relaxation rate decreases are present, they are less uniform and generally milder than in TLE-MTS. This further supports the hypothesis that TLE-no is a distinct clinicopathological entity from TLE-MTS and probably heterogeneous in itself. [source]

Prognostic Factors for the Surgery for Mesial Temporal Lobe Epilepsy: Longitudinal Analysis

Seizure Suppression by Adenosine A1 Receptor Activation in a Mouse Model of Pharmacoresistant Epilepsy

EPILEPSIA, Issue 7 2003
Nicolette Gouder
Summary: Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20,30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy. Methods: A mouse model for drug-resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl). Results: After injection of the selective adenosine A1 -receptor agonist, 2-chloro- N6 -cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of ,3.5 h after the injections. Seizure suppression was maintained when 8-sulfophenyltheophylline (8-SPT), a non,brain-permeable adenosine-receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern. Conclusions: This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug-resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures. [source]

Serum S-100 Protein Is Not a Suitable Seizure Marker in Temporal Lobe Epilepsy

EPILEPSIA, Issue 10 2002
Fritz Leutmezer
Summary: ,Purpose: S-100 protein is a sensitive marker of various brain diseases; however, its role in epilepsy is controversially discussed in the literature. We therefore studied the temporal profile of serial concentrations of S-100 protein in serum after secondarily generalized tonic,clonic seizures during video-EEG monitoring. Methods: Ten patients with mesial temporal lobe epilepsy were prospectively studied. Serum S-100 protein was measured after a seizure-free period of ,24 h (baseline) and 30 min, 3, 6, 12, and 24 h after a secondarily generalized tonic,clonic seizure of temporal lobe origin in nine and a convulsive status epilepticus in one patient. Results: All S-100 levels were within the normal range, except for those of one patient at baseline. Mean values were 0.045 ,g/L (range, 0.003,0.13 ,g/L) at baseline, 0.038 ,g/L (range, 0.003,0.09 ,g/L) at 30 min, 0.036 ,g/L (range, 0.003,0.08 ,g/L) at 3 h, 0.034 ,g/L (range, 0.003,0.07 ,g/L) at 6 h, 0.034 ,g/L (range, 0.003,0.08 ,g/L) at 12 h, and 0.035 ,g/L (range, 0.003,0.09 ,g/L) at 24 h after seizure offset. There were no significant differences between mean concentrations at any interval postictally. Conclusions: We could not detect any significant alterations in serum S-100 protein concentration either after a single secondarily generalized tonic,clonic seizure or after convulsive status epilepticus in patients with temporal lobe epilepsy. Our data do not confirm previous work, which suggested serum S-100 protein to be a suitable marker for epileptic seizures. [source]

FDG-PET Images Quantified by Probabilistic Atlas of Brain and Surgical Prognosis of Temporal Lobe Epilepsy

EPILEPSIA, Issue 9 2002
Sang Kun Lee
Summary: ,Purpose: This study evaluated the relation between hypometabolism, diagnosed by fluorodeoxyglucose positron emission tomography (FDG-PET), and the surgical outcome of a large and homogeneous series of cases of mesial temporal lobe epilepsy (mTLE), by using a probabilistic atlas of the human brain (statistical probabilistic anatomical maps: SPAM). Methods: Ninety-five surgically proven intractable mTLE patients and 22 age-matched controls were spatially normalized to the average brain PET template of international consortium of brain mapping (ICBM). The diagnosis of mTLE was confirmed by the presence of hippocampal sclerosis on magnetic resonance imaging (MRI) and video-EEG monitoring. Counts from normalized PET images were multiplied by the probability from 98 volumes of interest (VOIs) of SPAM. Asymmetric indexes (AIs) reflecting the severity of hypometabolism were calculated by counts of selected 12 VOIs from SPAM images in both temporal lobes. Extent of hypometabolism was determined by the number of voxels showing decreased metabolism in each VOI segmented by SPAM. Results: Of the 95 patients studied, 76 (80%) were seizure free, and 19 (20%) had postoperative seizures for the ,2-year follow-up period. No significant association between the severity of hypometabolism in each VOI of the temporal lobe and surgical outcome was identified (p > 0.05). The number of voxels showing decreased hypometabolism was not significantly different between the good- and poor-outcome groups (p > 0.05). Conclusions: Our results demonstrated that focal severity and extent of hypometabolism quantified by a probabilistic atlas of brain were not related to the surgical outcome in mTLE patients who had hippocampal sclerosis on MRI. We should develop a more localized and specified anatomic map for mTLE for further results. [source]

The Midline Thalamus: Alterations and a Potential Role in Limbic Epilepsy

EPILEPSIA, Issue 8 2001
Edward H. Bertram
Summary: ,Purpose: In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. Results: The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration. Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits. [source]

Magnetic Resonance Imaging Follow-up of Progressive Hippocampal Changes in a Mouse Model of Mesial Temporal Lobe Epilepsy

Down-regulation of protein l -isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

JOURNAL OF NEUROCHEMISTRY, Issue 3 2002
Julie Lanthier
Abstract Protein l -isoaspartyl methyltransferase (PIMT) repairs the damaged proteins which have accumulated abnormal aspartyl residues during cell aging. Gene targeting has elucidated a physiological role for PIMT by showing that mice lacking PIMT died prematurely from fatal epileptic seizures. Here we investigated the role of PIMT in human mesial temporal lobe epilepsy. Using surgical specimens of hippocampus and neocortex from controls and epileptic patients, we showed that PIMT activity and expression were 50% lower in epileptic hippocampus than in controls but were unchanged in neocortex. Although the protein was down-regulated, PIMT mRNA expression was unchanged in epileptic hippocampus, suggesting post-translational regulation of the PIMT level. Moreover, several proteins with abnormal aspartyl residues accumulate in epileptic hippocampus. Microtubules component ,-tubulin, one of the major PIMT substrates, had an increased amount (two-fold) of l -isoaspartyl residues in the epileptic hippocampus. These results demonstrate that the down-regulation of PIMT in epileptic hippocampus leads to a significant accumulation of damaged tubulin that could contribute to neuron dysfunction in human mesial temporal lobe epilepsy. [source]

Three-dimensional surface maps link local atrophy and fast ripples in human epileptic hippocampus,

ANNALS OF NEUROLOGY, Issue 6 2009
Jennifer A. Ogren PhD
Objectives There is compelling evidence that pathological high-frequency oscillations (HFOs), called fast ripples (FR, 150,500Hz), reflect abnormal synchronous neuronal discharges in areas responsible for seizure genesis in patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that morphological changes associated with hippocampal atrophy (HA) contribute to the generation of FR, yet there is limited evidence that hippocampal FR-generating sites correspond with local areas of atrophy. Methods Interictal HFOs were recorded from hippocampal microelectrodes in 10 patients with MTLE. Rates of FR and ripple discharge from each microelectrode were evaluated in relation to local measures of HA obtained using 3-dimensional magnetic resonance imaging (MRI) hippocampal modeling. Results Rates of FR discharge were 3 times higher in areas of significant local HA compared with rates in nonatrophic areas. Furthermore, FR occurrence correlated directly with the severity of damage in these local atrophic regions. In contrast, we found no difference in rates of ripple discharge between local atrophic and nonatrophic areas. Interpretation The proximity between local HA and microelectrode-recorded FR suggests that morphological changes such as neuron loss and synaptic reorganization may contribute to the generation of FR. Pathological HFOs, such as FR, may provide a reliable surrogate marker of abnormal neuronal excitability in hippocampal areas responsible for the generation of spontaneous seizures in patients with MTLE. Based on these data, it is possible that MRI-based measures of local HA could identify FR-generating regions, and thus provide a noninvasive means to localize epileptogenic regions in hippocampus. Ann Neurol 2009;66:783,791 [source]

A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: Seizure response, adverse events, and verbal memory,

ANNALS OF NEUROLOGY, Issue 2 2009
Nicholas M. Barbaro MD
Objective The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. Methods RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale,Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having "significant improvement," "no change," and "significant impairment" based on relative change indices. Results Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). Interpretation RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy. Ann Neurol 2009 [source]

Chromogranins as markers of altered hippocampal circuitry in temporal lobe epilepsy

ANNALS OF NEUROLOGY, Issue 2 2001
Susanne Pirker MD
Chromogranins are polypeptides which are widely expressed in the central nervous system. They are stored in dense core vesicles of nerve terminals, from where they are released upon stimulation. Using immunocytochemistry, we investigated the distribution of chromogranin A, chromogranin B, secretoneurin, and, for comparison, dynorphin in hippocampal specimens removed at routine surgery from patients with drug-resistant mesial temporal lobe epilepsy and in autopsy tissues from nonneurologically deceased subjects. In post mortem controls (n = 21), immunoreactivity for all four peptides (most prominently for chromogranin B and dynorphin) was observed in the terminal field of mossy fibers. For chromogranins, staining was observed also in sectors CA1 to CA3 and in the subiculum. Chromogranin B immunoreactivity was found in the inner molecular layer of the dentate gyrus, the area of terminating associational-commissural fibers. Secretoneurin and dynorphin immunoreactivity labeled the outer molecular layer and the stratum lacunosum moleculare of sectors CA1 to CA3, where projections from the entorhinal cortex terminate. In specimens with Ammon's horn sclerosis (n = 25), staining for all three chromogranins and for dynorphin was reduced in the hilus of the dentate gyrus. Instead, intense staining was observed in the inner molecular layer, presumably delineating terminals of sprouted mossy fibers. Specimens obtained from temporal lobe epilepsy patients without Ammon's horn sclerosis (n = 4) lacked this pronounced rearrangement of mossy fibers. In the stratum lacunosum moleculare of sector CA1, secretoneurin and dynorphin immunoreactivity was reduced in sclerotic, but not in nonsclerotic, specimens, paralleling the partial loss of fibers arising from the entorhinal cortex. Instead, presumably sprouted secretoneurin-immunoreactive fibers were found in the outer dentate molecular layer in sclerotic specimens. These changes in staining patterns for chromogranins and dynorphin mark profound plastic and functional rearrangement of hippocampal circuitry in temporal lobe epilepsy. [source]

Global Expression Profiling in Epileptogenesis: Does It Add to the Confusion?

BRAIN PATHOLOGY, Issue 1 2010
Yi Yuen Wang MBBS
Abstract Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results. [source]

Phenotypic characteristics of temporal lobe epilepsy: the impact of hippocampal sclerosis

ACTA NEUROLOGICA SCANDINAVICA, Issue 2009
K. Heuser
Objectives , Whether mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a condition with a unique biological background that can be delineated from other TLE, is unresolved. Here we performed a comparative analysis of two TLE patient cohorts , one cohort with HS and one without HS , in order to identify phenotypic characteristics specifically associated with MTLE-HS. Methods , Epidemiological data and clinical and diagnostic features were compared between patients with MTLE-HS and TLE patients without HS. When appropriate, data were compared with healthy controls. Results , Fifty-six (26%) patients were diagnosed with MTLE-HS and 162 (74%) with other TLE. Age at epilepsy onset was lower in patients with MTLE-HS (P = 0.003) than in TLE patients without HS. Incidence of simple partial seizures was higher in the MTLE-HS group (P = 0.006), as were complex partial seizures (P = 0.001), ictal psychiatric symptoms (P = 0.015), and autonomic symptoms (P < 0.001). Interictal psychiatric symptoms, including depression, were less frequent in MTLE-HS (P = 0.043). MTLE-HS patients had a higher incidence of childhood febrile seizures (FS; P = 0.043) than TLE patients without HS. In contrast, the former group had the lower frequency of first-grade family members with childhood FS (P = 0.019). Conclusions , We identified phenotypic characteristics that distinguish MTLE-HS from other types of TLE. These characteristics will be important in diagnostics, treatment, and determination of prognosis, and provide a basis for future phenotype,genotype studies. [source]

Temporal lobe magnetic resonance spectroscopic imaging following selective amygdalohippocampectomy for treatment-resistant epilepsy

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2005
D. C. Spencer
Objectives,,, Magnetic resonance spectroscopic imaging (MRSI) may show circumscribed or extensive decreased brain N -acetyl aspartate (NAA)/creatine and phosphocreatine (Cr) in epilepsy patients. We compared temporal lobe MRSI in patients seizure-free (SzF) or with persistent seizures (PSz) following selective amygdalohippocampectomy (SAH) for medically intractable mesial temporal lobe epilepsy (mTLE). We hypothesized that PSz patients had more extensive temporal lobe metabolite abnormalities than SzF patients. Materials and methods,,, MRSI was used to study six regions of interest (ROI) in the bilateral medial and lateral temporal lobes in 14 mTLE patients following SAH and 11 controls. Results,,, PSz patients had more temporal lobe ROI with abnormally low NAA/Cr than SzF patients, including the unoperated hippocampus and ipsilateral lateral temporal lobe. Conclusion,,, Postoperative temporal lobe MRSI abnormalities are more extensive if surgical outcome following SAH is poor. MRSI may be a useful tool to improve selection of appropriate candidates for SAH by identifying patients requiring more intensive investigation prior to epilepsy surgery. Future prospective studies are needed to evaluate the utility of MRSI, a predictor of successful outcome following SAH. [source]

Regional energetic dysfunction in hippocampal epilepsy

ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2005
J. W. Pan
Objectives , There is increasing evidence for a dysfunctional metabolic network in human mesial temporal lobe epilepsy (MTLE). To further describe this, we evaluated the bioenergetic status in unilateral MTLE inter-regionally and in relation to neuropathology. Materials and methods , We used whole brain high field (4 T) 31P MR spectroscopic imaging to determine in vivo PCr and ATP, studying n = 22 patients (all candidates for hippocampal resection) and n = 14 control volunteers. The degree of bioenergetic impairment was assessed by calculating the ratio of PCr to ATP. Results, Compared to controls, patients demonstrated significant decreases in PCr/ATP from the ipsilateral amygdala and pes (0.84 ± 0.14, 0.87 ± 0.10, respectively, patients vs 0.97 ± 0.15, 0.98 ± 0.16, controls). In patients, the ipsilateral thalamic energetics positively correlated with contralateral hippocampal energetics. In addition, the ipsilateral thalamic and striatal energetics negatively correlated with hippocampal total glial counts. Conclusions, These data are consistent with a view that in MTLE, the bilateral hippocampi, ipsilateral thalamus and striatum are linked in their energetic depression, possibly reflecting the propagation of seizures throughout the brain. [source]

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2004
M. Okujava
Objective ,, Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. Material and methods ,, Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. Results ,, Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). Conclusion ,, Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome. [source]