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Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy.

PURPOSE: Recent data suggested a role for glial cells in epilepsy. This study sought to identify and functionally characterize AMPA receptors expressed by astrocytes in human hippocampal tissue resected from patients with intractable temporal lobe epilepsy. METHODS: Patch-clamp and fast application methods were combined to investigate astrocytes in situ and after fresh isolation from the stratum radiatum of the hippocampal CA1 subfield. Relying on presurgical and histopathologic analysis, we divided human specimens into two groups, Ammon's horn sclerosis (AHS) and lesion-associated epilepsy. RESULTS: Fast application of glutamate and kainate evoked receptor currents in all cells studied. Reversal-potential analysis revealed an intermediate Ca2+ permeability of the receptor channels that did not vary between the two groups of patients. However, preapplication of the AMPA receptor-specific modulator, cyclothiazide, disclosed differences in flip-flop splicing. This treatment considerably enhanced the receptor conductance, with potentiation being significantly stronger in cells from AHS specimens compared with lesion-associated cells, suggesting upregulation of AMPA receptor flip splice variants in astrocytes of the sclerotic tissue. CONCLUSIONS: Compelling evidence has been accumulated showing direct and rapid signaling between neurons and glial cells. Our data suggest that in AHS patients, neuronally released glutamate will lead to an enhanced and prolonged depolarization of astrocytes, which might be involved in seizure generation and spread in this particular condition of human temporal lobe epilepsy.

Astrocytes↗

The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis.

OBJECTIVE: Prior studies on the predictive value of intraoperative electrocorticography (ECoG) have been performed on heterogeneous groups of patients with both temporal and extratemporal interictal spikes, lesional and nonlesional pathological findings, and variably extensive resections by different surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who underwent standard nontailored resections by one surgeon (RRG). All patients had only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis diagnosed by preoperative magnetic resonance imaging and confirmed by pathological examination of resected tissue. RESULTS: After a mean follow-up of 24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were seizure-free except for auras, and 8 (28%) who had any seizure after the 1st postoperative month. Fourteen patients (48%) had active interictal discharges outside the area of planned resection revealed by preresection ECoG. Neither the presence of these spikes nor their mean frequency correlated with seizure outcome. Eleven patients (38%) had residual spike discharges after resection, and 18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of these findings nor the mean spike frequency of residual or new spikes related to seizure outcome. Persistent spikes increased in frequency after resection in all outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal epileptiform activity intraoperatively is not useful in the surgical treatment of patients undergoing standard resection for medial temporal lobe epilepsy with magnetic resonance imaging evidence of mesial temporal sclerosis.

Adolescent↗

Properties of a delayed rectifier potassium current in dentate granule cells isolated from the hippocampus of patients with chronic temporal lobe epilepsy.

PURPOSE: Properties of potassium outward currents were investigated in human hippocampal dentate gyrus granule cells from 11 hippocampal specimens obtained from patients with temporal lobe epilepsy (TLE) during resective surgery. METHODS: Dentate granule cells were isolated enzymatically and outward currents analyzed by using the whole-cell configuration of the patch-clamp method. Hippocampal specimens were classified neuropathologically with respect to severe segmental cell loss, gliosis, and axonal sprouting (Ammon's horn sclerosis, AHS), or the presence of a focal lesion in the adjacent temporal lobe. RESULTS: A delayed rectifier outward current (IK), but not an A-type potassium current (IA) or inwardly rectifying potassium currents, was observed in all cells. The average current density of IK, the time-dependent decay of IK, and the resting membrane characteristics were not significantly different between patients with and without AHS. The voltage of half-maximal activation V1/2(act) was 5.4 +/- 1.8 mV in AHS compared with -2.9 +/- 1.8 mV in lesion-associated epilepsy (NS). In contrast, V1/2(inact) was shifted in a hyperpolarizing direction in AHS (-67.7 +/- 0.6 mV) compared with that in hippocampi not showing AHS (-47.7 +/- 2.6 mV; p = 0.0017). CONCLUSIONS: The altered steady-state voltage-dependence of IK may result in abnormal excitability of dentate granule cells in AHS and exert a marked influence on input-output properties of the dentate gyrus.

Adult↗

Variation in appearance of glioma on serial thallium-201 single photon emission computed tomography--case report.

A 63-year-old female presented with recurrent glioblastoma at the site of a right parietal glioblastoma which was diagnosed 1 year before. She was treated at that time by total removal of the tumor, irradiation, and chemotherapy. Four months after the initial treatment, serial thallium-201 single photon emission computed tomography (201Tl SPECT) showed increased uptake at the edge of the original tumor site. The index, the ratio of 201Tl uptake in the lesion to the normal brain, was 2.9 which suggested a recurrent tumor. Magnetic resonance images with gadolinium over the next 7 months demonstrated an enhanced mass lesion at the site of primary tumor resection and a new enhanced mass in the right temporal lobe. The lesion in the right parietal lobe had a 201Tl uptake index of 2.5, while the lesion in the right temporal lobe had an index of 1.5. Re-craniotomy and total resection of the tumors in the right parietal and temporal lobes were performed. The histological diagnosis of both tumors was glioblastoma. The proposed use of 201Tl SPECT for the differential diagnosis of recurrent glioma and radiation necrosis should be carefully considered because the 201Tl uptake index can vary in tumor with the same malignancy grade.

Brain Neoplasms↗

Surgical treatment for partial epilepsy among Norwegian children and adolescents.

We conducted a retrospective longitudinal self-controlled study of 64 patients aged 4-19 years treated with resective surgery for partial epilepsy from 1952 to 1988. Approximately 60% of patients experienced > 95% reduction in seizure frequency, and 70% had worthwhile improvement of at least 75% reduction. Seizure relief was more frequent among patients who underwent operation after 1978, and significant differences by time period of operation were noted for those with temporal lobe excisions and patients with normal tissue histology. The region of resection and the age at treatment did not provide significant information with respect to seizure outcome. Postresection electrocorticography (ECoG) and EEG of the first postoperative year predicted later seizure outcome. Small neurologic deficits were more common among patients resected in the temporal lobe than in patients resected in the frontal lobe. Half of the patients with preoperative unilateral focal activity and a third of those with bilateral focal activity had normal EEG postoperatively. One fourth had discontinued antiepileptic drug (AED) therapy. As expected, long-term mortality was significantly higher than the mortality of the general population. Seven patients died during follow-up. Two male patients committed suicide.

Adolescent↗

Postoperative EEG and seizure outcome in temporal lobe epilepsy surgery.

OBJECTIVE: To assess the prognostic value of scalp electroencephalogram (EEG) after epilepsy surgery, we investigated whether postoperative EEG abnormalities (interictal epileptiform discharges, IED; interictal slow activity, ISA) were associated with seizure outcome and other patient characteristics after resective surgery in patients with temporal lobe epilepsy (TLE). METHODS: Sixty-two patients with medically refractory TLE who underwent surgery were studied. Patients were categorized according to etiology (mesiotemporal sclerosis vs. tumors/cortical dysplasias); extent of surgical resection (extensive vs. limited); and amount of preoperative IED on wake EEG (oligospikers, <1 IED/h, vs. spikers). Patients were also classified as seizure-free (SF) or having persistent seizures/auras (not-SF) during follow up visits 1 month and 1 year after surgery. Preoperative 60-min interictal EEGs were evaluated for IED and ISA, and compared to postoperative wake EEGs. RESULTS: Seizures/auras persisted in 16/62 (25.8%) patients at 1 month and in 8/62 (12.9%) at 1 year follow up. ISA was not significantly related to outcome. Of 42 patients with EEG negative for IED at 1 month, 4 were not-SF; at 1 year, one of 44 such patients was not-SF. IED was significantly associated with seizure/aura persistence in patients categorized as mesiotemporal sclerosis and with extensive surgery. Oligospikers and spikers on preoperative EEG showed no differences in the postoperative seizure outcome, excellent in both cases; moreover, the presence of postoperative IEDs indicated auras/seizures persistence apart from the preoperative EEG spike frequency. CONCLUSIONS: Our study showed that the presence of IED of postoperatve EEG strongly indicates seizure/aura persistence. Therefore, serial EEGs should be included in postoperative follow up schedules as a crucial tool in evaluating seizure outcome.

Adolescent↗

Second operation after the failure of previous resection for epilepsy.

We present our surgical experience with second operations in 15 patients with recurrent intractable partial seizures after resection for epilepsy. The interval from the first operation until the first recurrence of seizures ranged from 1 day to 7 months (mean, 62 days). The interval between the first and second operations ranged from 3 months to 12 years (mean, 38 months). Detailed video-electroencephalographic interictal and ictal recording was performed in all patients (invasive electrodes were used in 11 patients). Ictal onset was shown to be remote from the zone of previous resection in 3 of 15 cases (all 3 extratemporal and in the ipsilateral hemisphere). Recurrent seizures arose from the area of previous extratemporal resection in 2 of 15 patients, and from the area of previous temporal resection in 10 of 15 patients. Both cases of extratemporal recurrences and 3 of the 10 cases of temporal lobe recurrences in the area of previous resection were associated with residual unresected structural lesion. Of the 10 patients with local temporal recurrence, 6 had proven epileptogenicity in the residual mesial structures, and 4 had residual epileptogenicity in the unresected lateral temporal lobe. The patients have been monitored for 8 to 82 months (mean, 18 months) after the second operation: 7 patients (47%) have remained seizure-free and another 5 (33%) have achieved a reduction in seizure frequency of more than 90%. There was no mortality or significant morbidity in this series. We conclude that the extent and distribution of residual epileptogenicity after failed epilepsy surgery are highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Musicogenic seizures can arise from multiple temporal lobe foci: intracranial EEG analyses of three patients.

PURPOSE: To determine the ictal-onset zone of musicogenic seizures by using intracranial EEG monitoring. METHODS: Musicogenic seizures in three patients with medically intractable musicogenic epilepsy were first localized by using noninvasive methods including, in one patient, ictal magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). The ictal-onset zones in these patients were then further localized using by intracranial EEG monitoring, and the outcomes of the two patients who underwent epilepsy surgery were determined. RESULTS: Patient 1's musicogenic seizures localized to the right lateral temporal lobe, patient 2's originated in the right mesial temporal lobe, and patient 3's arose independently from both mesial temporal lobes. Patients 1 and 2 underwent resective epilepsy surgery and are seizure free (Engel class I). CONCLUSIONS: Musicogenic epilepsy is a heterogeneous syndrome with seizures that can arise from multiple temporal lobe foci. Patients with medically intractable musicogenic epilepsy and with unilateral ictal onset zones may be considered candidates for resective epilepsy surgery.

Adult↗

Lateralized memory deficits on the Wada test correlate with the side of lobectomy only for patients with unilateral medial temporal lobe epilepsy.

The aim of this study was to determine whether the predictive value of the intracarotid amobarbital test (IAT) for the side to be resected is applicable only to medial temporal lobe epilepsy and to investigate whether there are different patterns of memory performances on the IAT between patients with unilateral mesial temporal sclerosis (UMT group) and those without (non-UMT group). We studied 30 patients in the UMT group and 10 in the non-UMT group, who underwent pre-surgical evaluation for intractable temporal lobe epilepsy. Memory performances on the IAT was defined as the percentage of memory items presented during unilateral hemispheric anesthesia that was recognized after recovery. More than a 20% decline of the memory performance on the IAT compared with the memory performance on the pre-test was regarded as a memory deficit. Age at onset of epilepsy was significantly younger in the UMT than in the non-UMT group. Surgical outcome was significantly better in the UMT than in the non-UMT group. The lateralizing value of unilateral memory deficits on the IAT was statistically confirmed. There was a significant association between falsely lateralizing memory performances and the non-UMT group. Excluding the exceptional cases with right-sided language dominance in spite of right-sided lesions, the high incidence of the unilateral right-sided memory deficits in the non-UMT group was statistically significant. This study suggested that the excellent lateralizing value of the memory performances on the IAT is limited to patients with mesial temporal lobe epilepsy. IAT memory performances in patients without such lesions can be misleading, even if lateralized, because their memory status presumably reflects a natural lateralization of the memory organization which is independent of the epileptogenic focus.

Adult↗

Diminished ability to interpret and report internal states after bilateral medial temporal resection: case H.M.

These experiments centered around H.M., a 54-year-old man who became amnesic 27 years ago after a bilateral resection in the medial temporal lobe region for epilepsy. In order to document the clinical reports that he rarely comments on such internal states as pain, hunger, and thirst, his thermal pain perception was examined in relation to his other somatosensory capacities, and his reports of hunger and thirst were assessed before and after meals. In order to investigate the effect of limited memory ability on the reporting of internal states, H.M.'s performance was compared with that of 5 other subjects with global amnesia. The results provided evidence that H.M.'s information about internal states is less available or less accessible than normal and that his impairment is not attributable to his well-documented memory deficit. Instead, it is believed that the bilateral resection of the amygdala accounts for H.M.'s poor appreciation of his internal states.

Adult↗

Exacerbation of vocal tics after temporal lobectomy.

We describe a woman with intractable temporal lobe epilepsy secondary to dysgenesis of the left temporal lobe who had a marked and long-term exacerbation of her preexisting vocal tics after a temporal lobectomy that completely controlled her seizures. The patient was determined to have right-sided speech dominance by the Wada test. This is, to our knowledge, only the second reported case of exacerbation of tics after resection of the nondominant temporal lobe.

Adult↗

Insular epilepsy. Similarities to temporal lobe epilepsy. Case report.

Insular epilepsy has been rarely reported and its clinical and electrographic features are poorly understood. The electrographic study of the insula is difficult since it is hidden from the brain surface by the frontal and temporal lobe. A 48 years-old woman started having simple partial autonomic and complex partial seizures with automatisms and ictal left arm paresis 8 years prior to admission. Seizure's frequency was 1 per week. Pre-operative EEG showed a right temporal lobe focus. Neuropsychological testing disclosed right fronto-temporal dysfunction. MRI showed a right anterior insular cavernous angioma. Intraoperative ECoG obtained after splitting of the sylvian fissure showed independent spiking from the insula and temporal lobe and insular spikes that spread to the temporal lobe. The cavernous angioma and the surrounding gliotic tissue were removed and the temporal lobe was left in place. Post-resection ECoG still disclosed independent temporal and insular spiking with a lower frequency. The patient has been seizure-free since surgery. Insular epilepsy may share many clinical and electroencephalographic features with temporal lobe epilepsy.

Brain Neoplasms↗

[A case of anaplastic astrocytoma arising 8 years after initial treatment by partial resection and irradiation for central neurocytoma].

A 31-year-old female developed the anaplastic astrocytoma in the right basal ganglia and temporal lobe 8 years after partial resection and irradiation of the central neurocytoma. Probably the malignant astrocytoma was an irradiation-induced tumor. Postoperative radiation therapy for the central neurocytoma appears to have a good effect on tumor local control. But it should be carefully decided whether to use radiation therapy for residual tumor because of the risk of delayed complications of irradiation, such as the present case.

Adult↗

Self-report of memory function in patients with temporal lobe epilepsy and temporal lobectomy.

Thirty-one surgical candidates with a unilateral temporal lobe seizure focus, 72 temporal lobectomy patients, 63 non-epileptic controls and their relatives, respectively, filled in the Memory Observation Questionnaire. The two patient groups rated their current memory similarly, but significantly worse than controls rated their own memory. Memory status was judged to be improved approximately three years after a temporal lobectomy. The relatives' ratings agreed with those of the patients. Thus patients who underwent surgical resection for relief of temporal lobe epilepsy did not report further subjective deterioration in memory compared to pre-operative cases. Laterality of excision did not affect self-report of general memory function. Nevertheless, a brief Verbal memory subscale yielded the expected material specific pattern after unilateral temporal lobectomy.

Adult↗

Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy.

To investigate the relationship of temporal lobe hypometabolism demonstrated on PET to surgical outcome and underlying pathology, we reviewed 30 consecutive epilepsy patients who underwent interictal PET studies with 18F fluorodeoxyglucose before temporal lobectomy. Two interpreters blindly reviewed the PET studies and graded them for degree, extent, and location of temporal lobe hypometabolism. Pathologic analysis of en bloc resected tissue showed mesial temporal sclerosis (n = 22), astrocytoma (n = 2), and no pathologic diagnosis (n = 6). Outcome (24 to 40 months' follow-up) was rated as seizure-free (21 patients), significantly improved (five patients), and not significantly improved (four patients). Both the degree and extent of the temporal lobe hypometabolism demonstrated on PET were strongly associated with subsequent seizure control. Pathologic findings, however, did not correlate with degree of PET hypometabolism or subsequent outcome. These data demonstrate that in patients judged to have temporal lobe epilepsy, the presence of temporal lobe hypometabolism is associated with a positive outcome after ipsilateral temporal lobectomy.

Adolescent↗

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.

Adult↗

Results of reoperation for failed epilepsy surgery.

A total of 37 patients who failed epilepsy surgery were evaluated with magnetic resonance imaging and long-term scalp electroencephalographic monitoring before reoperation. Repeat surgery involved focal resections after initial focal resections (30 cases) or stereotactic lesions (one case), or focal resections following anterior corpus callosotomy (six cases). Patients with initial focal resections followed by enlargement of the original operative site had the most successful outcome, especially those with complex partial seizures of temporal lobe origin. The most common cause for poor outcome of the original operation in patients with temporal lobe epilepsy was insufficient hippocampal resection. Patients who were most likely to benefit from reoperation were: 1) those with initially incompletely resected structural lesions; 2) those who were initially evaluated with invasive ictal monitoring; and 3) those who underwent further resection of the initial operative site rather than resection of a different cortical region.

Adolescent↗

Characterization of neocortical and hippocampal synaptosomes from temporal lobe epilepsy patients.

To investigate epilepsy-associated changes in the presynaptic terminal, we isolated and characterized synaptosomes from biopsies resected during surgical treatment of drug-resistant temporal lobe epilepsy (TLE) patients. Our main findings are: (1) The yield of synaptosomal protein from biopsies of epilepsy patients was about 25% of that from rat brain. Synaptosomal preparations were essentially free of glial contaminations. (2) Synaptosomes from TLE patients and naive rat brain, quickly responded to K(+)-depolarization with a 70% increase in intrasynaptosomal Ca(2+) ([Ca(2+)](i)), and a 40% increase in B-50/GAP-43 phosphorylation. (3) Neocortical and hippocampal synaptosomes from TLE patients contained 20-50% of the glutamate and gamma-aminobutyric acid (GABA) contents of rat cortical synaptosomes. (4) Although the absolute amount of glutamate and GABA released under basal conditions from neocortical synaptosomes of TLE patients was lower than from rat synaptosomes, basal release expressed as percentage of total content was higher (16.4% and 17.3%, respectively) than in rat (11.5% and 9. 9%, respectively). (5) Depolarization-induced glutamate and GABA release from neocortical synaptosomes from TLE patients was smaller than from rat synaptosomes (3.9% and 13.0% vs. 21.9% and 25.0%, respectively). (6) Analysis of breakdown of glial fibrillary acid protein (GFAP) indicates that resection time (anoxic period during the operation) is a critical parameter for the quality of the synaptosomes. We conclude that highly pure and viable synaptosomes can be isolated even from highly sclerotic human epileptic tissue. Our data show that in studies on human synaptosomes it is of critical importance to distinguish methodological (i.e., resection time) from pathology-related abnormalities.

Adult↗