Epileptiform activity extinguished by amygdala infusion of the neurotoxin ibotenate in a rat model of temporal lobe epilepsy

2002 ◽  
Vol 97 (2) ◽  
pp. 450-454 ◽  
Author(s):  
John R. Pace ◽  
Russell R. Lonser ◽  
R. Duncan Kirkby ◽  
Neal Jeffries ◽  
Michael A. Rogawski ◽  
...  

Object. The long-term antiseizure effects of local convection-enhanced infusion of the excitotoxin ibotenate were examined in a rat model of temporal lobe epilepsy. Methods. A single injection of kainate, an epileptogenic excitatory amino acid, into the left amygdala elicited chronic spontaneous recurrent seizure activity for at least 36 days after the injection. Two weeks after the injection, infusion of ibotenate, a nonepileptogenic excitatory amino acid that is an axon-sparing neuronal cell toxin, into the left amygdala and piriform lobe induced immediate and permanent extinction of electrical and behavioral seizure activity. Conclusions. Lesioning of an epileptic focus by convective distribution of ibotenate can produce an enduring suppression of seizure activity, indicating a chemical neurosurgical approach for epilepsy therapy.

2000 ◽  
Vol 93 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Guy M. McKhann ◽  
Julie Schoenfeld-McNeill ◽  
Donald E. Born ◽  
Michael M. Haglund ◽  
George A. Ojemann

Object. Among the variety of surgical procedures that are performed for the treatment of medically refractory mesial temporal lobe epilepsy (TLE), no consensus exists as to how much of the hippocampus should be removed. Whether all patients require a maximal hippocampal resection has not yet been determined.Methods. At the University of Washington, all TLE operations are performed in a tailored fashion, guided by electrocorticography (ECoG). The amount of hippocampal resection is determined intraoperatively by the extent of interictal epileptiform abnormalities on ECoG recorded from that structure, resulting in a hippocampal resection that is individualized for each patient. Using this approach, the authors prospectively observed 140 consecutive patients who underwent surgery for mesial TLE with pathological diagnoses of either mesial temporal sclerosis with neuronal loss (MTS group) or mild gliosis without neuronal loss (non-MTS group) to determine whether the extent of hippocampal resection correlates with outcome when a tailored approach is used. Additionally, the authors analyzed whether the presence of residual interictal epileptiform activity on ECoG following mesial temporal resection predicts poorer seizure control.With at least 18 months of clinical follow up, 67% of the 140 patients were seizure free or had only a single postoperative seizure. There was no correlation between the size of the hippocampal resection and seizure control in the group as a whole or when stratified by pathological subtype. Using an intraoperatively tailored strategy, individuals with a larger hippocampal resection (> 2.5 cm) were not more likely to have seizure-free outcomes than patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS patients, in whom postoperative ECoG detected residual epileptiform hippocampal (but not cortical or parahippocampal) interictal activity following surgical resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p = 0.002 in the non-MTS group).Conclusions. Intraoperative hippocampal ECoG can predict how much hippocampus should be removed to maximize seizure-free outcome, allowing for sparing of possibly functionally important hippocampus.


1970 ◽  
Vol 33 (3) ◽  
pp. 233-252 ◽  
Author(s):  
Murray A. Falconer

✓ The problem of childhood temporal lobe epilepsy is reviewed and illustrated from three cases in which the patients were freed from fits by temporal lobectomy. The pathological lesion (mesial temporal sclerosis) is discussed and the likelihood that many adult cases have gone unrecognized in childhood is emphasized.


2004 ◽  
Vol 101 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Aaron A. Cohen-Gadol ◽  
Jullie W. Pan ◽  
Jung H. Kim ◽  
Dennis D. Spencer ◽  
Hoby H. Hetherington

Object. Proton magnetic resonance (MR) spectroscopy imaging of the ratio of N-acetylaspartate (NAA) to creatine (Cr) has proved efficacious as a localizing tool in demonstrating the metabolic changes associated with temporal lobe epilepsy. To analyze the significance of these MR spectroscopy findings further, the authors explored the relationship between regional alterations in the NAA/Cr ratio in hippocampi measured preoperatively and histopathological findings in hippocampi resected in patients with intractable mesial temporal lobe epilepsy (MTLE). Methods. Twelve patients in whom the diagnosis of MTLE had been made and 12 healthy volunteers with no known history of neurological disease underwent high-resolution 1H MR spectroscopy imaging of NAA and Cr (0.64 cm3 nominal voxel resolution) in five voxels spanning the anteroposterior length of the hippocampus. The authors correlated the NAA/Cr ratio with neuropathological findings in resected hippocampi, specifically glial fibrillary acidic protein (GFAP) immunoreactivity and pyramidal neuronal loss. A linear regression analysis of the ipsilateral NAA/Cr ratio revealed a statistically significant relation to the extent of hippocampal neuronal loss in only the CA2 sector (correlation coefficient [r] = −0.66, p < 0.03). The ipsilateral NAA/Cr ratio displayed significant regressions with GFAP immunoreactivity from all the CA sectors (r values ranged from −0.69 and p < 0.01 for the CA4 sector to −0.88 and p < 0.001 for the CA2 sector) except for the CA1. The extent of neuronal cell loss in every hippocampal subfield (r = 0.71−0.74, p < 0.007), except the CA2 (p = 0.08), correlated to the extent of neuronal cell loss in the dentate gyrus. There was no significant relationship between the duration or frequency of seizures and the mean ipsilateral NAA/Cr ratio; however, the mean density of GFAP-immunopositive cells correlated with seizure frequency (p < 0.03). Conclusions. The NAA/Cr ratio may not measure the full extent of hippocampal neuronal cell loss. The significant association of the NAA/Cr ratio with the GFAP immunoreactivity of most CA sectors indicates that the NAA/Cr ratio may provide a more accurate measurement of recent neuronal injury caused by epileptic activity. The coupling between neuronal impairment and astroglial GFAP expression may indicate the close association between neuronal and glial dysfunction in patients with epilepsy.


1975 ◽  
Vol 43 (5) ◽  
pp. 596-607 ◽  
Author(s):  
John M. Van Buren ◽  
Cosimo Ajmone Marsan ◽  
Naomi Mutsuga

✓ The authors describe the use of temporal lobectomy following careful and repeated electroencephalogram (EEG) evaluation (with implanted electrodes in otherwise unresolvable cases) in the epileptic group characterized by automatisms (psychomotor seizures) with temporal epileptiform activity complicated by EEG foci in the opposite temporal lobe or by extratemporal activity. They found that this can render a significant number of patients (between 25% and 50%) either seizure-free or with significant and useful reduction in their seizure frequency. The cure and improvement rates of cases followed up after temporal resection with or without prior study with implanted electrodes were approximately equal. However, the implanted electrodes permitted surgical treatment of certain cases which would have been rejected on the basis of evidence derived from the scalp recordings alone. Of 28 of these 34 patients with persisting EEG epileptiform activity in the postoperative period, only one had such activity in a different location in a follow-up period of 6 years. No evidence of spreading epileptic activity or appearance of “mirror foci” was seen during a follow-up period averaging 8.2 years. Seizure remission up to 15 years with eventual recurrence of the original seizure type may occur following surgical therapy. Follow-up studies of surgical epileptic treatment of less than 3 to 5 years are of doubtful value.


2005 ◽  
Vol 103 (4) ◽  
pp. 768-769 ◽  
Author(s):  
Ross P. Carne ◽  
Terence J. O'Brien ◽  
Christine J. Kilpatrick ◽  
Lachlan R. MacGregor ◽  
Rodney J. Hicks ◽  
...  

Abstract Object. The syndrome of medial temporal lobe epilepsy (MTLE) may occur in patients in whom magnetic resonance (MR) images demonstrate normal findings. In these patients, there is no evidence of hippocampal sclerosis on neuroimaging, and histopathological examination of the resected hippocampus does not reveal significant neuron loss. In this paper the authors describe the distinct clinical features of this MTLE subtype, referred to as paradoxical temporal lobe epilepsy (PTLE). Methods. The authors selected 12 consecutive patients with preoperative findings consistent with MTLE in whom MR imaging did not demonstrate any hippocampal abnormality. Onset of hippocampal seizure was confirmed by long-term intracranial monitoring. There were six female and six male patients with a mean age of 32 ± 11 years (mean ± standard deviation [SD]) at presentation. These patients' seizure histories, available hippocampal volumetric measurements, and hippocampal cell densities in different subfields were reviewed. Sharp electrode recordings from dentate granule cells that had been maintained in hippocampal slices provided a measure of excitation and inhibition in the tissue. We compared these data with those of a cohort of 50 randomly selected patients who underwent anteromedial temporal resection for medial temporal sclerosis (MTS) during the same time period (1987–1999). The durations of follow up (means ± SDs) for the PTLE and MTS groups were 51 ± 59 months and 88 ± 44 months, respectively. A history of febrile seizure was present less frequently in the PTLE group (8%) than in the MTS group (34%). Other risk factors for epilepsy such as trauma, meningoencephalitis, or perinatal injuries were present more frequently in the PTLE group (50%) than in the MTS cohort (36%). In patients in the PTLE group the first seizure occurred later in life (mean age at seizure onset 14 years in the PTLE group compared with 9 years in the MTS group, p = 0.09). Ten patients (83%) in the PTLE cohort and 23 patients (46%) in the MTLE cohort had secondary generalization of their seizures. Among patients with PTLE, volumetric measurements (five patients) and randomized blinded visual inspection (seven patients) of the bilateral hippocampi revealed no atrophy and no increased T2 signal change on preoperative MR images. All patients with PTLE underwent anteromedial temporal resection (amygdalohippocampectomy, in five patients on the left side and in seven on the right side). Electrophysiological studies of hippocampal slices demonstrated that dentate granule cells from patients with PTLE were significantly less excitable than those from patients with MTS. The mean pyramidal cell loss in the CA1 subfield in patients in the PTLE group was 20% (range 0–59%) and that in patients in the MTS group was 75% (range 41–90%) (p < 0.001). Maximal neuron loss (mean loss 38%) occurred in the CA4 region in six patients with PTLE (end folium sclerosis). At the last follow-up examination, six patients (50%) in the PTLE group were seizure free compared with 38 patients (76%) in the MTS group. Conclusions. Clinical PTLE is a distinct syndrome with clinical features and surgical outcomes different from those of MTS.


2001 ◽  
Vol 95 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Warren Boling ◽  
Frederick Andermann ◽  
David Reutens ◽  
François Dubeau ◽  
Laetitia Caporicci ◽  
...  

Object. The goal of this study was to evaluate the efficacy of surgery for temporal lobe epilepsy (TLE) in older (≥ 50 years of age) patients. Methods. The authors conducted a review of all patients 50 years of age or older with TLE surgically treated at the Montreal Neurological Institute and Hospital since 1981 by one surgeon (A.O.). Only patients without a mass lesion were included. Outcome parameters were compared with those of younger individuals with TLE, who were stratified by age at operation. In patients aged 50 years and older, the onset of complex partial seizures occurred 5 to 53 years (mean 35 years) prior to the time of surgery. Postoperatively, over a mean follow-up period of 64 months, 15 patients (83%) obtained a meaningful improvement, becoming either free from seizures or only experiencing a rare seizure. Most surgery outcomes were similar in both older and younger individuals, except for a trend to more freedom from seizures and increased likelihood of returning to work or usual activities in the younger patients. Note that a patient's long-standing seizure disorder did not negatively affect their ability to achieve freedom from seizures following surgery. Conclusions. Surgery for TLE appears to be effective for older individuals, comparing favorably with results in younger age groups, and carries a small risk of postoperative complications.


2002 ◽  
Vol 97 (5) ◽  
pp. 1125-1130 ◽  
Author(s):  
Erol Veznedaroglu ◽  
Elisabeth J. Van Bockstaele ◽  
Michael J. O'Connor

Object. Several lines of evidence have demonstrated a number of cellular changes that occur within the hippocampus in patients with temporal lobe epilepsy (TLE). These include aberrant migration of granule cells and sprouting of mossy fibers, processes that have been linked to the hyperexcitability phenomenon observed in cases of TLE. In the present study the authors examined brain tissues obtained in patients undergoing temporal lobectomy surgery and in patients at autopsy (normal human control specimens), and compared the subcellular composition of regions of the hippocampus containing dispersed granule cells. Methods. Six human hippocampi were obtained in patients undergoing temporal lobectomies for intractable seizures. The patients ranged in age from 24 to 50 years. Two of the six patients had a history of head trauma and one had experienced a febrile seizure during childhood. Immediately following excision from the brain, the tissue was placed in an acrolein—paraformaldehyde fixative. The hippocampi were processed along with six human brain control specimens obtained at autopsy for light and electron microscopic evaluation. The tissues were then labeled for collagen types I through IV. Positive collagen labeling was identified, with the aid of both light and electron microscopy, in the parenchyma of all patients with TLE but not in the control tissues. Conclusions. The authors report the first localization of collagen outside of the vasculature and meninges in the brains of patients with TLE. Recent evidence of collagen's chemoattractant properties and its role in epileptogenesis in animal models suggests that collagen may play a role in cellular migration and seizure activity in a subset of patients. Further studies with a larger series of patients are warranted.


1998 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Bhaskara Rao Malla ◽  
Terence J. O'Brien ◽  
Gregory D. Cascino ◽  
Elson L. So ◽  
Kurupath Radhakrishnan ◽  
...  

Object. Recurrence of seizures immediately following epilepsy surgery can be emotionally devastating, and raises concerns about the chances of successfully attaining long-term seizure control. The goals of this study were to investigate the frequency of acute postoperative seizures (APOS) occurring in the 1st postoperative week following anterior temporal lobectomy (ATL) to identify potential risk factors and to determine their prognostic significance. Methods. One hundred sixty consecutive patients who underwent an ATL for intractable nonlesional temporal lobe epilepsy were retrospectively studied. Acute postoperative seizures occurred in 32 patients (20%). None of the following factors were shown to be significantly associated with the occurrence of APOS: age at surgery, duration of epilepsy, side of surgery, extent of neocortical resection, electrocorticography findings, presence of mesial temporal sclerosis, and hippocampal volume measurements (p > 0.05). Patients who suffered from APOS overall had a lower rate of favorable outcome with respect to seizure control at the last follow-up examination than patients without APOS (62.5% compared with 83.6%, p < 0.05). The type of APOS was of prognostic importance, with patients whose APOS were similar to their preoperative habitual seizures having a significantly worse outcome than those whose APOS were auras or were focal motor and/or generalized tonic—clonic seizures (excellent outcome: 14.3%, 77.8%, and 75%, respectively, p < 0.05). Only patients who had APOS similar to preoperative habitual seizures were less likely to have an excellent outcome than patients without APOS (14.3% compared with 75%, p < 0.05). Timing of the APOS and identification of a precipitating factor were of no prognostic importance. Conclusions. The findings of this study may be useful in counseling patients who suffer from APOS following ATL for temporal lobe epilepsy.


1992 ◽  
Vol 77 (2) ◽  
pp. 201-208 ◽  
Author(s):  
René Tempelhoff ◽  
Paul A. Modica ◽  
Kerry L. Bernardo ◽  
Isaac Edwards

✓ Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 µg · kg−1 (mean 25.75 µg · kg−1). More importantly, four of these eight seizures occurred initially in the “healthy” temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection.


2001 ◽  
Vol 94 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Johannes Schramm ◽  
Thomas Kral ◽  
Thomas Grunwald ◽  
Ingmar Blümcke

Object. The goal of this paper was to describe the clinical and surgical aspects of a group of patients suffering from drug-resistant neocortical temporal lobe epilepsy (TLE), as well as seizure outcomes and factors affecting seizure outcomes in these patients. Methods. This study was based on data prospectively collected and retrospectively evaluated. Sixty-two patients with neocortical TLE constituted the study population. Only patients who underwent corticectomies, lesionectomies, lateral anterior lobe resections, and/or multiple subpial transections were included. The pathological areas resected in these patients could be separated into three groups composed of 35 neoplastic lesions, 23 nonneoplastic lesions, and three nonlesional areas. The mean duration of follow-up review in these patients was 21.9 ± 14 months. Outcomes were categorized according to Engel classes. Class I was found in 79% of the patients and Class II in 11%. Invasive presurgical evaluation was performed in 43% of the patients. There were only temporary complications (3.3% surgical and 1.6% neurological) and no deaths. In summary, lesions confirmed on histological examination were rarely found in patients with neocortical TLE. Low-grade tumors were the most commonly found lesions in these patients and the most common tumor was ganglioglioma. Outcome was best for those patients with neoplastic lesions and was independent of the duration of their seizures. Outcome was little influenced by the type of resection performed and was found to be as good as that achieved in patients with mesial TLE. Conclusions. These results demonstrate that the concept of lateral or neocortical TLE as a distinct entity is useful. Surgery for neocortical TLE can be considered a viable treatment option that is associated with a low morbidity rate and good outcomes.


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