Biomedical subjects

Sang Kun Lee

Publications and source records attributed to Sang Kun Lee.

At least 19 recordsLinked to original sources

PubMed2025

Prediction of personalized antiseizure medications response based on clinical signatures in epilepsy.

Despite the increasing number of available antiseizure medications (ASMs), optimal medical therapy is still a process of trial and error. We aimed to predict the responsiveness of various ASMs based on initial tests using artificial intelligence. The study consisted of 2586 patients fulfilling the following criteria: (1) first visit to the epileptologists from 2008 to 2017, (2) a diagnosis of epilepsy, and 3) ≥ three years of follow-up duration. The clinical characteristics, ASM history, seizure frequency, laboratory, EEG, and MRI results, were collected. Machine algorithms were utilized to predict the responsiveness of specific regimens. Valproate showed the highest area under curve (AUC), 0.636. The AUCs of levetiracetam, oxcarbazepine, and lamotrigine were 0.614, 0.633, and 0.674. The AUCs of common dual regimens were 0.543 for levetiracetam + oxcarbazepine, 0.454 for levetiracetam + valproate, and 0.583 for levetiracetam + lamotrigine. Levetiracetam + carbamazepine showed the highest AUC, 0.686. In Shapley Additive exPlanations analysis, seizure type significantly impacted prediction performance for valproate responsiveness, and onset age and disease duration for lamotrigine. The prediction performances for the response based on initial data differ according to ASMs. An enormous dataset from a multicenter would improve the prediction power of ASM responsiveness in the future.

Humans↗

PubMed2006

Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation.

BACKGROUND AND PURPOSE: Astrocytic glutamate transporter protein, GLT-1 (EAAT2), recovers extracellular glutamate and ensures that neurons are protected from excess stimulation. Recently, beta-lactam antibiotics, like ceftriaxone (CTX), were reported to induce the upregulation of GLT-1. Here, we investigated ischemic tolerance induction by CTX in an experimental model of focal cerebral ischemia. METHODS: CTX (200 mg/kg per day, IP) was administered for 5 consecutive days before transient focal ischemia, which was induced by intraluminal thread occlusion of the middle cerebral artery for 90 minutes or permanently. RESULTS: Repeated CTX injections enhanced GLT-1 mRNA and protein expressions after 3 and 5 days of treatment, respectively. CTX-pretreated animals showed a reduction in infarct volume by 58% (reperfusion) and 39% (permanent), compared with the vehicle-pretreated animals at 24 hours postischemia (P<0.01). Lower doses of CTX (20 mg/kg per day and 100 mg/kg per day) reduced infarct volumes to a lesser degree. The injection of GLT-1 inhibitor (dihydrokainate) at 30 minutes before ischemia ameliorated the effect of CTX pretreatment. However, CTX administration at 30 minutes after ischemia produced no significant reduction in infarct volume. CTX reduced the levels of proinflammatory cytokines (tumor necrosis factor-alpha, FasL), matrix metalloproteinase (MMP)-9, and activated caspase-9 (P<0.01). In addition, CTX-pretreated animals showed better functional recovery at day 1 to week 5 after ischemia (P<0.05). CONCLUSIONS: This study presents evidence that CTX induces ischemic tolerance in focal cerebral ischemia and that this is mediated by GLT-1 upregulation.

Animals↗

PubMed2006

Ictal SPECT in neocortical epilepsies: clinical usefulness and factors affecting the pattern of hyperperfusion.

INTRODUCTION: The aims of this analysis were to: (1) determine the value of ictal SPECT in the localization of neocortical epileptogenic foci, (2) evaluate the relationships between the results of ictal SPECT and other potential affecting factors, and (3) compare traditional visual analysis and the subtraction method. METHODS: We retrospectively analyzed 81 consecutive patients with neocortical epilepsy who underwent epilepsy surgery and achieved a favourable surgical outcome, including 36 patients with normal MRI. Side-by-side visual analysis and subtraction images were classified as correctly localizing,correctly lateralizing, or non-localizing/non-lateralizing images according to the resected lobe. RESULTS: Side-by-side visual analysis and subtraction SPECT correctly localized the epileptogenic lobe in 58.9% and 63.0% of patients, respectively. The two methods were complementary and the diagnostic sensitivity of ictal SPECT using the two methods was 79.0%. Ictal SPECT using the visual method correctly localized the epileptogenic lobe more frequently in patients with a localizing pattern of ictal scalp EEG at the time of radioligand injection. When using subtraction images, an injection delay of less than 20 s after seizure onset was significantly correlated with correct localization. The subtraction method was superior to the visual method for localizing frontal lobe epilepsy (FLE) and parietal lobe epilepsy (PLE), and in patients with non-localizing/non-lateralizing EEG at onset. CONCLUSIONS: Ictal SPECT analyses using visual and subtraction methods are useful and complementary for the localization of the epileptogenic foci of neocortical epilepsy. Early radioligand injection and ictal EEG patterns are related to ictal SPECT localization. The subtraction method may be more useful in some epileptic syndromes.

Adolescent↗

PubMed2006

Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

Recent evidences suggest key roles of abnormal neurogenesis and astrogliosis in the pathogenesis of epilepsy. Alterations in the microenvironment of the stem cell, such as microglial activation and cyclooxygenase-2 induction may cause ectopic neurogenesis or astrogliosis. Here, we examined if inflammatory blockade with celecoxib, a selective cyclooxygenase-2 inhibitor, could modulate the altered microenvironment in the epileptic rat brain. Celecoxib attenuated the likelihood of developing spontaneous recurrent seizures after pilocarpine-induced prolonged seizure. During the latent period, celecoxib prevented neuronal death and microglia activation in the hilus and CA1 and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. The direct inhibition of precursor cells by celecoxib was further demonstrated in human neural stem cells culture. These findings raise the evidence of COX-2 induction to act importantly on epileptogenesis and suggest a potential therapeutic role for COX-2 inhibitors in chronic epilepsy.

Animals↗

PubMed2006

Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy.

The variability of P-glycoprotein expression in individuals is linked to a C3435T polymorphism of the multidrug-resistance 1 (MDR1) gene, and the CC genotype at the C3435T polymorphism was reported to be associated with multidrug resistance in epilepsy patients. Since population frequencies of polymorphic genes depend on ethnic specificity, we investigated functional significance of the C3435T polymorphism of the MDR1 gene in Korean epilepsy patients. One hundred and eight patients with drug-responsive epilepsy, 63 patients with drug-resistant epilepsy, and 219 control migraine subjects were studied, but the analysis for C3435T allele showed no significant association between the CC genotype and the multidrug-resistant epilepsy. We suggest that influence of the C3435T polymorphism in the multidrug-resistant epilepsy may not be significant in Korean populations and further investigations in various ethnic populations would be necessary to clarify the effect of C3435T polymorphism on the mutidrug resistance in epilepsy patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Prognostic factors in neocortical epilepsy surgery: multivariate analysis.

PURPOSE: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery. METHODS: One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status >or=2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors. RESULTS: The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p<0.05). Multivariate analysis revealed that a focal lesion on MRI (p=0.003), correct localization by FDG-PET (p=0.007), and localized ictal onset on EEG (p=0.01) were independent predictors of a good outcome. CONCLUSIONS: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.

Adult↗

PubMed2005

Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy.

Surgical treatment of cryptogenic neocortical epilepsy is challenging. The aim of this study was to evaluate surgical outcomes and to identify possible prognostic factors including the results of various diagnostic tools. Eighty-nine patients with neocortical epilepsy with normal magnetic resonance imaging (35 patients with frontal lobe epilepsy, 31 with neocortical temporal lobe epilepsy, 11 with occipital lobe epilepsy, 11 with parietal lobe epilepsy, and 1 with multifocal epilepsy) underwent invasive study and focal surgical resection. Patients were observed for at least 2 years after surgery. The localizing values of interictal electroencephalogram (EEG), ictal scalp EEG, interictal 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and subtraction ictal single-photon emission computed tomography were evaluated. Seventy-one patients (80.0%) had a good surgical outcome (Engel class 1-3); 42 patients were seizure free. Diagnostic sensitivities of interictal EEG, ictal scalp EEG, FDG-PET, and subtraction ictal single-photon emission computed tomography were 37.1%, 70.8%, 44.3%, and 41.1%, respectively. Localization by FDG-PET and interictal EEG was correlated with a seizure-free outcome. The localizing value of FDG-PET was greatest in neocortical temporal lobe epilepsy. The focalization of ictal onset and also ictal onset frequency in invasive studies were not related to surgical outcome. Concordance with two or more presurgical evaluations was significantly related to a seizure-free outcome.

Adolescent↗

PubMed2005

Surgical outcome of epilepsy caused by cortical dysplasia.

PURPOSE: Cortical dysplasia (CD) is the second most common pathologic entity in surgically treated epilepsy. To delineate its surgical outcome and prognostic factors, we performed a retrospective analysis of patients operated on at a single institute. METHODS: Between September 1994 and December 2000, 128 cases with CD were operated on at our institute. The male/female ratio was 85:43, and the mean age was 27 years (SD, 7.6 years). The mean postoperative follow-up period was 26.9 months (SD, 12.0 months). Seizure outcome and severity of CD were classified according to Engel's and Mischel's classifications, respectively. Severity of CD was mild in 69, moderate in 21, and severe in 38. Lobar distribution was temporal in 54, frontal in 48, and others in 26. Cortical resection, lobectomy, or hemispherectomy was done in all patients. Univariate analysis was done followed by multivariate analysis by using computerized statistical software. RESULTS: Postoperative seizure outcome was Engel class I in 58 (45.3%), II in 17 (13.3%), III in 16 (12.5%), and IV in 37 (28.9%). Transient postoperative complications occurred in 14 (10.9%) patients without mortality or permanent neurologic impairment. Multivariate analysis revealed severity of CD and frontal lobe resection as independent prognostic factors for worse outcome (p = 0.001 and 0.003, respectively). CONCLUSIONS: Epilepsy surgery for CD achieved 45.3% seizure-free rate with 10.9% transient postoperative complications in our institute. Worse postoperative seizure outcome was observed in cases with mild CD and frontal lobe resection.

Adolescent↗

PubMed2005

Prognostic factors for the surgery for mesial temporal lobe epilepsy: longitudinal analysis.

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 degrees 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 degrees 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.

Adolescent↗

PubMed2005

Occipital lobe epilepsy: clinical characteristics, surgical outcome, and role of diagnostic modalities.

PURPOSE: To assess the role of various diagnostic modalities, to identify surgical prognostic factors and concordances with presurgical evaluations, and to characterize the clinical features of occipital lobe epilepsy (OLE), we studied 26 patients who were diagnosed as having OLE and underwent epilepsy surgery. METHODS: Diagnoses were established by standard presurgical evaluations, which included magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), ictal single-photon emission computed tomography (SPECT), scalp video-EEG monitoring, and intracranial EEG monitoring. After epilepsy surgery, patients were followed up for >2 years. RESULTS: Sixteen (61.5%) of the 26 became seizure free after surgery, and another eight patients had a favorable outcome. Sixteen of the 26 patients experienced a type of visual aura (i.e., visual hallucination, visual illusion, blindness, or a field defect). Nine patients had both automotor seizures and secondary generalized tonic-clonic seizures at different times. Interictal EEG showed correctly localizing spikes in 10 of the 16 patients who became seizure free, and in three of the 10 non-seizure-free patients. MRI correctly localized the lesion in seven of these 16 seizure-free patients, and in three of the 10 non-seizure-free patients. FDG-PET correctly localized the lesion in eight of the 16 seizure-free patients, and in three of nine non-seizure-free patients. Ictal SPECT was performed in 19 patients and correctly localized the lesion in only three of 12 seizure-free patients, and in four of seven non-seizure-free patients. Ictal EEG correctly localized the lesion in 13 of the 16 seizure-free patients, and in five of the 10 non-seizure-free patients. No significant relation was found between the diagnostic accuracy of any modality and surgical outcome. The localizations of epileptogenic zones by these different diagnostic methods were complementary. The concordance of three or more modalities was significantly observed in seizure-free patients (p = 0.042). However, no definite relation was observed between the presence of lateralizing clinical seizure manifestation and surgical outcome (p = 0.108). CONCLUSIONS: Some specific auras indicated an occipital epilepsy onset. Various diagnostic methods can be useful to diagnose OLE, and a greater concordance between presurgical evaluation modalities indicates a better surgical outcome.

Adolescent↗

PubMed2004

Parietal lobe epilepsy: surgical treatment and outcome.

OBJECTIVE: Parietal lobe epilepsy (PLE) is neither common nor easily diagnosed because of its variable clinical features. To elucidate its characteristics and surgical outcome, the authors reviewed their surgical experiences. METHODS: Between September 1994 and August 2001, 38 patients with PLE received surgical treatment at the Seoul National University Hospital. All patients underwent resection, mainly involving the parietal lobe. RESULTS: Preoperatively, over 60% of the cases were not considered to be PLE, even though PLE was the most common diagnosis (15/38, 39.8%). An invasive study was performed in 37 of the 38 patients. Awake operations under regional anesthesia were performed in 20 patients (52.6%). Seizure disappeared in 15 (Engel's classification I, 39.5%), and rare seizure remained in 5 (Engel II, 13.2%). Thirteen patients showed a worthwhile improvement (Engel III, 34.2%), whereas 5 exhibited no worthwhile improvement (Engel IV, 13.2%). Pathologies were diverse, the most common being cortical dysplasia (94.3%). CONCLUSION: Since PLE is difficult to diagnose preoperatively, an invasive study covering the parietal lobe is mandatory, if PLE is suspected. Cortical dysplasia was the most common etiology, thus awake operation under regional anesthesia and intraoperative brain mapping is helpful during extensive resection in order to spare the eloquent cortex.

Adolescent↗

PubMed2004

Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats.

Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and beta galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-beta gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.

Aggression↗

PubMed2004

Probabilistic map of blood flow distribution in the brain from the internal carotid artery.

Brain single photon emission computed tomographic (SPECT) images acquired after injecting Tc-99m-HMPAO into the internal carotid artery (ICA) during an intracarotid amobarbital procedure (IAP SPECT) provide anatomical information on the blood flow distribution from the ICA. In this study, probabilistic maps of the distribution of blood supply from the ICA were developed using the IAP SPECT images. Twenty-two sets of basal and IAP SPECT were collected from an existing database. IAP SPECT images were coregistered to basal SPECT images, and spatial normalization parameters used for basal SPECT images were reapplied to IAP SPECT for anatomical standardization. Pixel counts of IAP SPECT images were then normalized, and the probabilistic map of cerebral perfusion distribution (perfusion probabilistic map) for each hemisphere was determined by averaging the spatial/count-normalized IAP SPECT images. Population-based probabilistic maps representing the extent of ICA territory (extent probabilistic map) were also composed by averaging the binary images obtained by thresholding the spatially normalized IAP SPECT images. The probabilistic maps were used to quantify cerebral perfusion and reserve change after arterial bypass surgery in 10 patients with ICA stenosis. In the probabilistic maps, blood supply from the ICA was found to be most likely in the dorsolateral frontal lobe, the anterosuperior portion of the temporal lobe, and in the frontoparietal area. Of the subcortical regions, the striatum was found to be most likely to derive its blood supply from ICA. In patients with cerebral occlusive disease, improvements in basal perfusion and perfusion reserve in the bypass-grafted ICA territory were well identified and were increased by 6.2% and 4.6%, respectively, on average. The probabilistic maps developed in this study illustrate the perfusion distribution and extent of vascular territory for ICA and would be useful for objective evaluations of perfusion status in cerebrovascular disease.

Adolescent↗

PubMed2004

Diffusion changes suggesting predominant vasogenic oedema during partial status epilepticus.

Diffusion-weighted imaging (DWI) has demonstrated a focal area of cytotoxic oedema during partial status epilepticus (PSE). However, vasogenic oedema related to the breakdown of the blood-brain-barrier (BBB) and ictal hyperperfusion could be the predominant DWI findings in the epileptogenic area during PSE. We report a case of PSE with ictal aphasia, right hemiparesis, and repetitive focal motor seizure of the right side. T2-weighted image (T2WI) and apparent diffusion coefficient (ADC) maps obtained during PSE showed an increased signal in the left temporo-parietal area, indicative of vasogenic oedema. EEG documented the ictal activities and single photon emission tomography (SPECT) showed asymmetrically increased perfusion in the corresponding area. Follow-up T2WI, DWI, and ADC maps obtained 3 months later showed the disappearance of the previous abnormalities. However, T2WI showed cortical atrophy and newly developed white matter changes in the corresponding area. This case shows that DWI findings may be variable during PSE, dependent on the predominance of cytotoxic and vasogenic oedema.

Aged↗

PubMed2004

Role of immediate postictal diffusion-weighted MRI in localizing epileptogenic foci of mesial temporal lobe epilepsy and non-lesional neocortical epilepsy.

OBJECTIVE: To determine whether meaningful changes in signal intensity or in the apparent diffusion coefficient of water (ADC) in the ictal onset zone can be detected through immediate postictal and interictal diffusion-weighted magnetic resonance imaging (DWMRI) in patients with localization-related epilepsy. METHOD: In randomly selected 10 medial and lateral temporal lobe epilepsy (TLE) and four extratemporal epilepsy patients, DWMRI was performed immediately after a seizure and during the interictal period. All 14 patients were non-lesional except for hippocampal sclerosis detected on MRI. The mean time interval from seizure onset to postictal DWMRI was 81 min. Regions of interest (ROI) were selected in both the cortex, which was believed to be the ictal onset zone, and the corresponding anatomical region of the contralateral hemisphere in the postictal and interictal DWMRI. The mean ADC measured from all ROIs was compared. Ictal onset zones were determined by ictal electroencephalography (EEG) and seizure semiology. RESULTS: On visual inspection of postictal and interictal DWMRI, signal changes in the ictal onset zone could be identified in only one patient with medial TLE. The mean ADC values from the ictal onset zones were not significantly different from those of the corresponding contralateral regions of the cortices in both postictal and interictal DWMRI. However, the postictal ADC values of the epileptogenic foci of neocortical epilepsy or neocortical temporal portion of TLE without hippocampal sclerosis were decreased compared with interictal ones in whom both interictal and postictal DWMRIs were obtained (P = 0.028). CONCLUSION: Our results demonstrate that water diffusion can change even after a single seizure in non-lesional neocortical epilepsy.

Adolescent↗

PubMed2004

Parietal lobe epilepsy: the semiology, yield of diagnostic workup, and surgical outcome.

PURPOSE: To characterize the clinical features, the prognostic value, and diagnostic sensitivities of various presurgical evaluations and the surgical outcomes in parietal lobe epilepsy (PLE), we describe 40 patients who were diagnosed as having PLE, including 27 surgically treated patients. METHODS: The diagnosis was established by means of a standard presurgical evaluation, including magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), ictal single-photon emission tomography (SPECT), and scalp video-electroencephalography (EEG) monitoring, with additional intracranial EEG monitoring in selected cases. RESULTS: Among the 40 patients, 27 experienced at least one type of aura. The most common auras were somatosensory (13 patients), followed by affective, vertiginous, and visual auras. The patients had diverse manifestations. Eighteen patients showed simple motor seizure, followed by automotor seizure, and dialeptic seizure. Two patients manifested generalized tonic-clonic seizures only, and 19 patients experienced more than one type of seizure. The surgical outcome was favorable in 22 of 26 patients including 14 who were seizure free. Patients with localized MRI abnormality had a higher probability to be seizure free, with marginal significance (p = 0.062), whereas other diagnostic modalities failed to predict the surgical outcome. In the seizure-free group, localization sensitivity was 64.3% by MRI, 50% by PET, 45.5% by ictal SPECT, and 35.7% by ictal EEG. The concordance rate of the various diagnostic modalities was higher in the seizure-free group than in the non-seizure-free group, although it did not reach statistical significance. CONCLUSIONS: Seizures, in the case of PLE, can manifest themselves in a wider variety of ways than was previously thought. Surgical outcome was favorable in most of the patients. MRI abnormality and concordance of different diagnostic modalities were associated with high seizure-free rate.

Adolescent↗

PubMed2004

Continuous cytosine-b-D-arabinofuranoside infusion reduces ectopic granule cells in adult rat hippocampus with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

Brief or prolonged seizures induce various patterns of plasticity. Axonal or dendritic remodelling and development of ectopic granule cells have been described in the hilus and molecular layer of the adult rodent hippocampus. Hippocampal cell proliferation also occurs after seizures. However, whether the seizure-induced cell proliferation plays a pathological or reparative role in the epileptic brain is unknown. In this study, we attempted to suppress the seizure-induced cell proliferation with the antimitotic agent cytosine-b-D-arabinofuranoside (Ara-C) and to examine the development of spontaneous recurrent seizures (SRS). Experimental status epilepticus was induced with pilocarpine, and Ara-C or vehicle alone was infused continuously with an osmotic minipump. SRS were video-monitored. BrdU immunohistochemistry was used for the spatial and temporal analysis of hippocampal cell proliferation, and double labelling with NeuN, calbindin and GFAP antibodies was performed for the differentiation of BrdU-positive cells. Timm staining was also performed for evaluation of mossy fibre sprouting (MFS). With continuous Ara-C infusion, the likelihood of developing SRS was decreased and, during the latent period, the development of ectopic granule cells in the hilus and new glia in the CA1 area was reduced when compared with the vehicle-infused group, while MFS was not altered. The results suggest that the hippocampal cell proliferation plays a pro-epileptogenic role rather than a compensatory role, and that the epileptogenic process may be associated with the generation of new glia in the CA1 area and/or new neurons in the dentate gyrus, particularly the ectopically located hilar granule cells.

Animals↗

PubMed2004

Adding or repositioning intracranial electrodes during presurgical assessment of neocortical epilepsy: electrographic seizure pattern and surgical outcome.

OBJECT: The aim of this study was to investigate changes in electroencephalography (EEG) patterns obtained from added or repositioned electrodes after those initially implanted had failed to indicate the true local ictal onset zone. The authors focused on the following matters: rationale for adding or repositioning electrodes, topographic and frequency characteristics of ictal onset before and after adding or repositioning electrodes, the effect of the procedures, and the relationship between changes in intracranial EEG onset patterns and surgical outcomes. METHODS: Of 183 patients with intracranial recordings, 18 experienced repositioning of existing or implanting of additional electrodes 7 or 10 days later. All patients underwent resection and were followed up for more than 1 year. In particular, the relationship between surgical outcome and distribution/frequency of intracranial seizure onset was analyzed. Results of noninvasive presurgical evaluations in patients who had undergone single and double invasive studies were also evaluated. By adding or repositioning electrodes, a new ictal onset zone was revealed in 13 patients. In another four, the second evaluation led to a change in defining the resection margin. Ictal onset in the partially sampled area, simultaneous or independent onset in two separate areas, and onset in the distal end of the electrode strip or grid were common reasons for failing to localize the ictal onset zone during the initial evaluation. Seven of 11 patients who were ultimately found to have a focal ictal onset zone on the second evaluation became seizure free after the operation. Only one of six patients with a regional ictal onset zone identified on the second evaluation became seizure free. There was no relationship between the frequency of the ictal rhythm and surgical outcome. Note, however, that surgical outcome was more favorable in patients who had undergone a single invasive study than in those who had undergone double invasive studies. The patients who needed a second evaluation had less localizing information and less concordant results on presurgical evaluations. When comparing nonlesional cases, surgical outcomes were not significantly different among patients with a single invasive study and those with double invasive studies. No additional morbidity or death occurred during the second study. CONCLUSIONS: The addition or reposition of intracranial electrodes with a short-term interval should be considered in selected patients. Spatial restriction of the ictal onset rhythm identified on repeated evaluation is the most important predictor of a good surgical outcome.

Adolescent↗