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PubMed2001

[Surgery for intractable epilepsy in children: pre- and perioperative evaluations with special reference to dipole tracing method estimated from interictal spike].

Methods of preoperative and perioperative evaluation methods for surgical treatment of intractable epilepsy in children are described. Among non-invasive diagnostic methods, EEG-video monitoring is the most fundamental. Amygdalohippocampal volume measurement by MR was useful for the differential diagnosis of mesial temporal lobe epilepsy (TLE) from lateral TLE and generalized epilepsy. The dipole tracing method with a realistic head model was useful for identification of epileptic foci from the interictal spikes of scalp EEG, when an abnormal electric source was estimated as an equivalent current dipole (ECD) in the brain of patients with organic lesion and TLE. ECD concentration ratio ranged from 70 to 90% within 20 mm around the lesion. After lesionectomy seizures disappeared in every patient. The mean distance between the centers of the ECD and epileptic focus (identified by subdural electrode recording) was 14 mm (range: 8 to 18 mm). ECDs of mesial TLE were located in the temporal base rather than mesial temporal lobe, whereas those of lateral TLE in the lateral cortex precisely. In unilateral, intermediate and bilateral TLE, 76%, 52% and 36% of ECDs were localized in the ictal onset zone respectively (p = 0.007). Electrical cortical stimulation with chronically placed intracranial electrodes was used to accurately identify eloquent areas to avoid postsurgical complications. Immediately after operation, 10 to 20% of patients showed better or deteriorated results in neuropsychological examinations, which recovered in all patients after one year. Postoperative seizures were absent in three fourths of patients. Further efforts are needed to obtain better seizure control in future.

Adolescent↗

PubMed2004

Unitemporal vs bitemporal hypometabolism in mesial temporal lobe epilepsy.

BACKGROUND: Patients with mesial temporal lobe epilepsy (TLE) often show bilateral temporal hypometabolism (BTH), but the nature of this finding has not been well established. OBJECTIVE: To compare the clinical characteristics between unitemporal hypometabolism (UTH) and BTH patients in mesial TLE. DESIGN: Cross-sectional study. SETTING: Epilepsy center at university hospital in Seoul, Korea. PATIENTS: We enrolled 95 patients with mesial TLE, 87 of whom had subsequently undergone surgery. Seizures, interictal and ictal electroencephalography (EEG), brain magnetic resonance imaging, Wada test, and neuropsychological test results were reviewed. (18)F-fluorodeoxyglucose positron emission tomography scans were interpreted visually. Patients were divided into 2 groups: UTH and BTH. RESULTS: There were 59 UTH patients and 36 BTH patients. Semiologic analysis showed that UTH patients had higher frequencies of aura and unilateral dystonic posturing, whereas BTH patients had higher frequencies of a nonlateralized bilateral ictal EEG pattern and bilateral interictal spikes. Moreover, BTH patients had more frequent symmetric Wada memory scores and white matter changes in the bilateral temporal lobes on brain magnetic resonance imaging than UTH patients. All UTH patients with bilateral TLE on scalp EEG showed unilateral seizure onset on intracranial EEG. CONCLUSIONS: The characteristic clinical findings of mesial TLE with BTH were a more frequent nonlateralized ictal EEG pattern, bitemporal interictal spikes, symmetric Wada memory score, and the anterior temporal white matter changes, and less frequent aura and unilateral dystonic posturing. Surgical outcomes were similar and good in both groups, although surgery could not be performed in 8 BTH patients (22%).

Adult↗

PubMed2007

Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy.

Molecular biology tools have been employed to investigate the participation of peptides in human temporal lobe epilepsy (TLE). Active polypeptides and their receptors have been related to several brain processes, such as inflammation, apoptosis, brain development, K(+) and Ca(2+) channels' activation, cellular growth, and induction of neuronal differentiation. Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE. The present work was delineated to analyze the kinin B1 and B2 receptors expression in the hippocampus of patients presenting refractory mesial TLE. The hippocampi were removed during the patients surgery in a procedure used for seizure control and compared with tissues obtained after autopsy. Nissl staining was performed to study the tissue morphology and immunohistochemistry, and Western blot was used to compare the distribution and levels of both receptors in the hippocampus. In addition, real time PCR was employed to analyze the gene expression of these receptors. Nissl staining showed sclerotic hippocampi with hilar, granular, and pyramidal cell loss in TLE patients. Immunohistochemistry and Western blot analyses showed increased expression of kinin B1 and B2 receptors but the real-time PCR data demonstrated increased mRNA level only for kinin B2 receptors, when compared with controls. These data show for the first time a relationship between human TLE and the kallikrein-kinin system, confirming ours previous results, obtained from experimental models of epilepsy.

Adult↗

PubMed2004

Synaptosomal glutamate and GABA transport in patients with temporal lobe epilepsy.

High-affinity glutamate and GABA transporters found in the plasma membrane of neurons and glial cells terminate neurotransmission by rapidly removing extracellular transmitter. Impairment of transporter function has been implicated in the pathophysiologic mechanisms underlying epileptogenesis. We characterized glutamate and gamma-aminobutyric acid (GABA) transport in synaptosomes, isolated from neocortical and hippocampal biopsies of patients with temporal lobe epilepsy (TLE). We analyzed K(+)-evoked release in the presence and absence of Ca(2+) to determine vesicular and transporter-mediated release, respectively. We also analyzed (3)H-glutamate and (3)H-GABA uptake, the effect of glutamate uptake inhibitors L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and DL-threo-beta-benzyloxyaspartate (TBOA), and GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (SK&F 89976-A). Neocortical synaptosomes from TLE patients did not show vesicular glutamate release, strongly reduced transporter-mediated release, and an increased basal release compared to that in rat synaptosomes. Furthermore, basal release was less sensitive to tPDC, and (3)H-glutamate uptake was reduced compared to that in rat synaptosomes. Vesicular GABA release from neocortical synaptosomes of TLE patients was reduced compared to that in rat synaptosomes, whereas transporter-mediated release was hardly affected. Furthermore, basal GABA release was more than doubled, but neither basal nor stimulated release were increased by SK&F 89976-A, which did significantly increase both types of GABA release in rat synaptosomes. Finally, (3)H-GABA uptake by synaptosomes from TLE patients was reduced significantly in hippocampus (0.19 +/- 0.04%), compared to that in neocortex (0.32 +/- 0.04%). Control experiments with human peritumoral cortical tissue suggest that impaired uptake of glutamate, but not of GABA, was caused in part by the hypoxic state of the biopsy. Our findings provide evidence for impaired function of glutamate and GABA transporters in human TLE.

Amino Acid Transport System X-AG↗

PubMed1993

Verbal recognition memory performance in unilateral temporal lobe epilepsy.

Recognition memory performance of 91 left and right unilateral temporal lobe epilepsy (TLE) patients was examined prior to and post anterior temporal lobectomy. The left TLE group showed more impaired response discrimination ability than the right TLE group; however, their false positive rate varied as a function of distractor type. Prior to temporal lobe resection, false positives were higher for semantically related distractors (novel or from an interference list) than for semantically unrelated items from an interference list, phonemic distractors, or unrelated errors. Following temporal lobe resection, only novel semantically related distractors in the left TLE group showed a significant increase in false positives, and they were also significantly higher than all other error types. The results of this study suggest that the left TLE patients have impaired individual item recollection in the context of intact information about basic semantic attributes.

Adult↗

PubMed2002

Ipsilateral Reorganization of Language in Early-Onset Left Temporal Lobe Epilepsy.

Purpose. Decline in confrontation naming ability occurs in a subset of temporal lobe epilepsy (TLE) patients following left (dominant) anterior temporal lobectomy (ATL). Patients with late age of onset of seizures are most vulnerable to such decline. In addition, object names typically acquired later in language development are the words most likely to be inaccessible after ATL. Early-onset left TLE patients may be at lower risk for post-ATL dysnomia either because they have a limited preoperative lexicon that does not include most late-age-of-acquistion names or they undergo early ipsilateral language reorganization, which results in a lexicon similar to that of late-onset TLE patients but offers protection from post-ATL naming decline.Methods. Sixty-five left hemisphere speech dominant left TLE patients who had undergone ATL were assessed pre- and postoperatively on the Boston Naming Test (BNT).Results. The early- and late-onset groups performed similarly across three BNT age-of-acquisition categories at the preoperative assessment. Words acquired relatively later in life were most likely to become inaccessible postoperatively for both groups, but the early-onset patients showed significantly less overall postoperative decline in naming ability compared with the late-onset group.Conclusions. The more stable pre- to postoperative naming performance exhibited by early-onset patients cannot be attributed to lack of acquisition of the words shown to be most vulnerable to postoperative decline (i.e., late-age-of-acquisition words). Their object naming stability suggests that early-onset left TLE patients undergo intrahemispheric reorganization of language early in life that provides protective benefits.

Journal Article↗

PubMed1990

Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epilepsy relief.

It has been reported that hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 +/- 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symptoms. Long-lasting (27 months) normoprolactinemia (19.4 +/- 0.6 ng/ml) and TLE relief were achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 micrograms/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.

Adult↗

PubMed2006

White matter abnormalities in the anterior temporal lobe suggest the side of the seizure foci in temporal lobe epilepsy.

INTRODUCTION: White matter abnormalities in the anterior temporal lobe (WAATL) are sometimes observed on magnetic resonance (MR) images of patients with temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in TLE patients. METHODS: We reviewed 112 consecutive patients with medically intractable TLE. We compared the side of seizure foci on EEG (preoperative and intraoperative) and MR images. RESULTS: Both loss of gray-white matter demarcation and increased signal intensity changes in the anterior white matter (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were present on the same side as the seizure foci on preoperative intracranial EEG with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG) in all the patients. In 47 patients, MR images showed WAATL and focal lesions that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45 patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion were on the same side. In three patients, no focal lesions were seen but WAATL were present on the same side as the seizure foci on sEEG and ECG. In four patients, MR images showed focal lesions for which epileptogenicity was questionable, and WAATL on the same side as the seizure foci on EEG. CONCLUSION: WAATL are clinically useful because they indicate the side of the seizure foci.

Adolescent↗

PubMed1999

An increase of hippocampal calretinin-immunoreactive neurons correlates with early febrile seizures in temporal lobe epilepsy.

Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS). Previous data demonstrate an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are transiently expressed in the murine developing hippocampus and are critically involved in neuronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally oriented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal formation have been visualized by antibodies against the calcium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hippocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher levels of CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a considerable number of TLE patients with AHS display signs of impaired hippocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It remains to be elucidated, how these changes contribute to the pathogenesis of TLE.

Adolescent↗

PubMed1990

Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy.

The distribution of granule cells in the dentate gyrus of the hippocampal formation was studied in control autopsy and temporal lobe epilepsy (TLE) specimens. In control tissue, the granule cell somata were closely approximated and formed a narrow lamina with a distinct, regular border with the molecular layer. In 11 of 15 TLE specimens, the granule cell somata were dispersed and formed a wider than normal granule cell layer. The granule cell somata extended into the molecular layer to varying extents, creating an irregular boundary between the lamina. The dispersed granule cells were frequently aligned in columns, and many of these neurons displayed elongated bipolar forms. The extent of granule cell dispersion appeared to be related to the amount of cell loss in the polymorph layer of the dentate gyrus. Granule cell dispersion was not consistently associated with granule cell loss although 5 of the 11 specimens with granule cell dispersion also showed moderate to marked granule cell loss. The most common features in the histories of the TLE cases with granule cell dispersion were severe febrile seizures or seizures associated with meningitis or encephalitis during the first 4 years of life. The dispersion of the granule cells suggests that there has been some alteration in the patterns of cell migration in a subpopulation of cases with severe TLE. The resultant ectopic positions of the granule cells could lead to changes in both the afferent and efferent connections of these neurons and, thus, contribute to the altered circuitry of the hippocampal formation in TLE.

Adolescent↗

PubMed1995

The pathophysiologic relationships between lesion pathology, intracranial ictal EEG onsets, and hippocampal neuron losses in temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) lesion patients the pathology, location of intracranial ictal EEG onsets, and hippocampal neuron losses were compared. Patients (n = 63) were classified into: (1) Tumors (n = 26, e.g. astrocytomas, gangliogliomas); (2) vascular (n = 9, e.g. cavernous and venous angiomas); (3) developmental (n = 17, e.g. cortical dysplasia, heterotopias); or (4) atrophic (n = 11, e.g. cortical or white matter encephalomalacia). Other variables were; (1) the location of the temporal lesion in the mesial to lateral, and anterior to posterior plane, (2) a clinical history of an initial precipitating injury (IPI) prior to the onset of TLE (e.g. prolonged first seizure, head trauma), (3) hippocampal neuron densities, (4) focal or regional location by intracranial depth EEG of ictal onsets, and (5) seizure outcomes. Results showed that severe hippocampal neuron losses were associated with two statistically significant findings. First, patients with mesial lesions in or adjacent to the body of the hippocampus had greater neuron losses compared to mesial lesions anterior or posterior to the hippocampus (P = 0.04). Second, lesion patients with an IPI history had greater Ammon's horn (AH) neuron losses compared to those without IPI histories (P = 0.0005), and the profile of loss was similar to hippocampal sclerosis (HS). Granule cell losses correlated in a complex manner in that; 1) by regression analysis densities decreased with longer intervals of TLE (P = 0.006), (2) tumor patients with IPIs had less granule cell loss compared to those without IPIs intervals of TLE (P = 0.006), (2) tumor patients with IPIs had less granule cell loss compared to those without IPIs (P = 0.05), and (3) developmental patients with IPIs had greater granule cell loss than patients without IPIs (P = 0.009). Mesial-temporal depth EEG electrodes were the first areas of ictal activity in 15 of 16 patients (94%), and greater hippocampal neuron losses were not associated with focal mesial-temporal EEG onsets. Seizure outcomes were worse in tumor patients compared to HS patients (P = 0.01), and patients with post-resection seizures had incomplete resections of their lesions and/or hippocampi. These results indicate that in TLE lesion patients the amount and pattern of hippocampal neuron loss depends on the location of the lesion, the pathologic classification, and a history of an IPI. Further, despite variable neuron losses, in temporal lesion patients the hippocampus was nearly always involved in the genesis or propagation of the chronic seizures.

Case-Control Studies↗

PubMed2005

Reading abilities and cognitive functions of children with epilepsy: influence of epileptic syndrome.

Children with epilepsy are at risk of developing learning disorders. To explore the influence of the epileptic syndrome on reading abilities, we have compared the neuropsychological profile of 12 children with benign idiopathic epilepsy with rolandic spikes, 10 with temporal lobe epilepsy and 12 with idiopathic generalized epilepsy. Children underwent a selection of standardised tests designed to assess: oral language, reading, short-term memory, attention and behavioural adjustment. Analysis of variance was adjusted according to age of onset of the epileptic syndrome, duration of the syndrome, and performance IQ for each group. Children with temporal lobe epilepsy (TLE) had significantly lower scores for reading speed and comprehension, but epileptic variables (the age of onset of epilepsy, duration and activity of epilepsy) had influenced academic performances. In the TLE group there was a clear effect of the topography of the epileptic foci (left-side TLE vs. right-side TLE) on reading profile. Furthermore, the effect of epileptic syndromes was found in phonological, semantic and verbal working memory deficits in the TLE group. To a lesser extent children with idiopathic generalized epilepsy (IGE) also exhibit cognitive deficit. The results of the present study lend support to epilepsy-specific patterns of neuropsychological dysfunction in children that should be considered to improve remediation of academic underachievement in these populations.

Adolescent↗

PubMed2004

Recurrent nightmares and disorders of arousal in temporal lobe epilepsy.

Sleep is known to be severely altered in temporal lobe epilepsy (TLE). Furthermore, sleep deprivation is one of the key factors contributing to cognitive deficits and drug resistance in TLE. In the past, "non-ictal" parasomnias, as well as parasomnia-like nocturnal episodes ultimately diagnosed as seizures, have been documented in epileptic patients. However, recurrence of possibly "ictal" parasomnias in TLE has not been adequately appreciated. Through questionnaires and diaries distributed to TLE patients and their families in a tertiary center for epilepsy, 20 out of 168 patients seen in the last 2 years have been identified as, probands and extensively recorded during sleep. Patients presented with confusional arousals were 16, 14 with nightmares, and 2 with sleep walking episodes. Episodes (25) corresponding to clinical or subclinical seizures have been video-polygraphically recorded in 10/20 patients. Therapy optimization, pharmacological or surgical, resolved the episodes in 17/20 patients. A better seizure control with improved quality of life can be achieved by increasing and extending the practice of nocturnal recording in TLE patients.

Adolescent↗

PubMedDate not supplied

Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients.

RATIONALE: Altered expression of glutamate transporter EAAT2 protein has been reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis. METHODS: By RT-PCR we studied the occurrence of I7R and E9S in neocortical and hippocampal specimens from TLE patients and non-neurological controls. RESULTS: Both splice forms were found in all neocortical specimens from TLE patients (100% I7R, 100% E9S). This was significantly more than in controls (67% I7R, 60% E9S; P < 0.05). We also detected I7R and E9S in all seven motor cortex post-mortem samples from patients with amyotrophic lateral sclerosis. Within the TLE patient group, both splice variants appeared significantly more in non-sclerotic (100%), than in sclerotic hippocampi (69%, P < 0.05). CONCLUSION: These data indicate that the epileptic brain, especially that of TLE patients without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA splicing. Our data confirm that the presence of alternative EAAT2 splice forms is not disease specific.

Adult↗

PubMed2004

Chronic temporal lobe epilepsy: spatial extent and degree of metabolic dysfunction studied with magnetic resonance spectroscopy (MRS).

INTRODUCTION: Proton magnetic resonance spectroscopy ((1)H MRS) has been proposed as a lateralizing method for the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). Studies have shown correlations between temporal lobe (TL) NAA and seizure frequency, and TL NAA/Cr and the duration of epilepsy in patients with TLE. This latter finding may suggest that progressive neuronal dysfunction may occur in both temporal lobes in patients with TLE, even when the seizures originate in only one temporal lobe. We analyzed our data in an attempt to find a possible correlation between extension of neuronal dysfunction based on NAA measures and duration of epilepsy. METHODS: We studied 45 consecutive patients with the diagnosis of TLE, who were referred for presurgical evaluation. Duration of epilepsy was defined as the interval between the age of seizure onset and the time of the MRS examination. All studies were performed in the inter-ictal state, prior to intracranial monitoring or resection. We performed two-tailed Pearson correlation analysis between ipsilateral NAA/Cr and extension of the abnormality (voxels involved) and the duration of the seizure disorder in years. RESULTS: The average duration of epilepsy in this group was 20 years. No significant correlation was found between duration of epilepsy and mean hippocampal NAA/Cr (r=-.131, p=.390); nor was a correlation found between duration of epilepsy in years or the extent of metabolic lesion (voxels involved) (r=-.264, p=.079). CONCLUSIONS: Hippocampal NAA/Cr does not correlate with duration of epilepsy in TLE. Our findings suggest that cross-sectional group measures of hippocampal neuronal function do not suggest damage progression.

Adolescent↗

PubMed2004

Epilepsy induced by extended amygdala-kindling in rats: lack of clear association between development of spontaneous seizures and neuronal damage.

Most patients with temporal lobe epilepsy (TLE), the most common type of epilepsy, show pronounced loss of neurons in limbic brain regions, including the hippocampus, amygdala, and parahippocampal regions. Hippocampal damage in patients with TLE is characterized by extensive neuronal loss in the CA3 and CA1 sectors and the hilus of the dentate gyrus. There is a long and ongoing debate on whether this type of hippocampal damage, referred to as hippocampal sclerosis, is the cause or consequence of TLE. Furthermore, hippocampal damage may contribute to the progressive features of TLE. The present study was designed to determine whether development of spontaneous recurrent seizures (SRS) after extended kindling of the amygdala in rats is associated with neuronal damage. The kindling model of TLE was chosen because previous studies have shown that only part of the rats develop SRS after extended kindling, thus allowing to compare the brain pathology of rats that received the same number of amygdala stimulation but did or did not develop SRS. For extended kindling, rats were stimulated twice daily 3-5 days a week for up to about 280 stimulations. During long-term EEG/video monitoring, SRS were observed in 50% of the rats over the period of extended kindling. SRS often started with myoclonic jerks or focal seizures and subsequently progressed into secondarily generalized seizures, so that the development of SRS recapitulated the earlier kindling of elicited seizures. No obvious neurodegeneration was observed in the CA1 and CA3 sectors of the hippocampus, the amygdala, parahippocampal regions or thalamus. A significant bilateral reduction in neuronal density was determined in the dentate hilus after extended kindling, but this reduction in hilar cell density did not significantly differ between rats with and without observed SRS. Determination of the total number of hilar neurons and of hilar volume indicated that the reduced neuronal density in the dentate hilus was due to expansion of hilar area but not to neuronal damage. The data demonstrate that extended kindling does not cause any hippocampal damage resembling hippocampal sclerosis, but that SRS develop in the absence of such damage.

Amygdala↗

PubMed2006

Evidence of tumor necrosis factor receptor 1 signaling in human temporal lobe epilepsy.

Seizures, particularly when prolonged, may cause neuronal loss within vulnerable brain structures such as the hippocampus, in part by activating programmed (apoptotic) cell death pathways. Experimental modeling suggests that seizures activate tumor necrosis factor receptor 1 (TNFR1) and engage downstream pro- and anti-apoptotic signaling cascades. Whether such TNFR1-mediated signaling occurs in human temporal lobe epilepsy (TLE) is unknown. Presently, we examined this pathway in hippocampus surgically obtained from refractory TLE patients and contrasted findings to matched autopsy controls. Western blotting established that total protein levels of the TNFR1 proximal signaling adaptor TNFR-associated protein with death domain (TRADD), cleaved initiator caspase-8 and apoptosis signal-regulating kinase 1 (ASK1) were higher in TLE samples than controls. Intracellular distribution analyses revealed raised cytoplasmic levels of TNFR1, TRADD and the caspase-8 recruitment adaptor Fas-associated protein with death domain (FADD), and higher levels of TRADD and cleaved caspase-8 in the microsomal fraction, in TLE samples. Immunoprecipitation studies detected TRADD-FADD binding, and fluorescence microscopy revealed TRADD co-localization with FADD in TLE hippocampus. These data suggest that TNFR1 signaling is engaged in the hippocampus of patients with refractory temporal lobe epilepsy.

Adult↗

PubMed2004

Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus.

While it is clear that acute hippocampal injury or status epilepticus increases the production of new neurons in the adult dentate gyrus (DG), the effects of chronic epilepsy on dentate neurogenesis are unknown. We hypothesize that epileptogenic changes and spontaneous recurrent motor seizures (SRMS) that ensue after hippocampal injury or status epilepticus considerably decrease dentate neurogenesis. We addressed this issue by quantifying the number of cells that are positive for doublecortin (DCX, a marker of new neurons) in the DG of adult F344 rats at 16 days and 5 months after an intracerebroventricular kainic acid (ICV KA) administration or after graded intraperitoneal KA (IP KA) injections, models of temporal lobe epilepsy (TLE). At early post-KA administration, the injured hippocampus exhibited increased dentate neurogenesis in both models. Conversely, at 5 months post-KA administration, the chronically epileptic hippocampus demonstrated severely declined neurogenesis, which was associated with considerable SRMS in both KA models. Additionally, stem/progenitor cell proliferation factors, FGF-2 and IGF-1, were decreased in the chronically epileptic hippocampus. Interestingly, the overall decrease in neurogenesis and the extent of SRMS were greater in rats receiving IP KA than rats receiving ICV KA, suggesting that the extent of neurogenesis during chronic TLE exhibits an inverse relationship with SRMS. These results provide novel evidence that chronic TLE is associated with extremely declined dentate neurogenesis. As fraction of newly born neurons become GABA-ergic interneurons, declined neurogenesis may contribute to the increased seizure-susceptibility of the DG in chronic TLE. Likewise, the hippocampal-dependent learning and memory deficits observed in chronic TLE could be linked at least partially to the declined neurogenesis.

Animals↗