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Objective: Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity., Methods: Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected., Results: The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml)., Significance: Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy., (© 2022 International League Against Epilepsy.)

Objective: This study was undertaken to examine long-term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open-label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968)., Methods: Patients who completed the 12-week, multicenter, multinational, double-blind, randomized, placebo-controlled C013 study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment-emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan-Meier analysis., Results: One hundred forty-nine patients entered the OLE (median duration of cenobamate treatment = 6.25 years). As of the data cutoff, 57% of patients (85/149) remained in the OLE (median treatment duration = 6.8 years, range = 6.4-7.8 years). The median modal daily cenobamate dose was 200 mg (range = 50-400 mg). The probability of treatment continuation at 1-6 years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1 year (n = 107), the probability of continuing at Years 2-5 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29/149), adverse event (10.1%, 15/149), and lack of efficacy (5.4%, 8/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2/149), ataxia (1.3%, 2/149), and memory impairment or amnesia (1.3%, 2/149). Dizziness (32.9%, 49/149), headache (26.8%, 40/149), and somnolence (21.5%, 32/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity., Significance: Long-term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years in adults with treatment-resistant focal seizures taking one to three ASMs., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

To treat intractable cases of autoimmune encephalitis, the need for novel immunotherapy that penetrates the blood-brain barrier (BBB) is increasing. Tofacitinib is a Janus kinase (JAK) inhibitor used to treat refractory immune-mediated diseases that effectively penetrates the BBB. Accordingly, tofacitinib could be a new option for patients with refractory autoimmune encephalitis. Patients treated with tofacitinib were selected from Seoul National University Hospital cohort for autoimmune encephalitis from April 2019 until July 2020. We retrospectively analyzed the efficacy of tofacitinib in patients with autoimmune encephalitis who showed insufficient responses to multimodal conventional immunotherapies. Tofacitinib was administered orally at a dose of 5 mg twice daily. A total of eight patients were treated with tofacitinib; two had good responses (clinical global impression-improvement score [CGI-I] = 1 or 2), three had partial responses (CGI-I = 3), and three showed no significant improvements (CGI-I = 4) in response to tofacitinib. The two good responders showed the improvement of chronic autoimmune meningoencephalitis and the cessation of the new-onset refractory status epilepticus in anti-myelin oligodendrocyte glycoprotein (MOG)-associated disorder, which was previously intractable to anesthetics and the other immunotherapies. No patients had serious side effects. Our findings suggest the potential of tofacitinib as a therapeutic option for central nervous system autoimmune diseases., (© 2021 International League Against Epilepsy.)

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4-6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: -30.32%, P = 0.0017; -30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non-Asian population (-35.07%, P = 0.0001; -37.78%, P < 0.0001; -34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, -37.37%, P = 0.0139; non-Asian, -27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non-Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non-Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

This open-label, multicenter, randomized phase IV trial (NCT01498822) of noninferiority design compared the long-term effectiveness, safety, and tolerability of levetiracetam (LEV) monotherapy with those of oxcarbazepine (OXC) monotherapy in adults with newly diagnosed focal epilepsy. Korean patients (16-80 years), with ≥2 unprovoked focal seizures in the year preceding the trial, who had not taken any antiepileptic drugs (AEDs) in the last 6 months, were randomized to receive LEV or OXC (1:1). Effectiveness, safety, and tolerability were assessed over a 50-week period. Treatment failure rates (per protocol set) were 15/118 (12.7%) in the LEV-treated group and 30/128 (23.4%) in the OXC-treated group, an absolute difference of -10.7% (95% confidence interval [CI] -20.2, -1.2). Because the upper 95% CI limit was less than the pre-specified noninferiority margin of 15%, LEV was considered noninferior to OXC. Twenty-four-week and 48-week seizure freedom rates were 53.8% and 34.7% for LEV vs. 58.5% and 40.9% for OXC. Both LEV and OXC were well tolerated, with 8.7% and 8.6% of patients reporting serious treatment-emergent adverse events, respectively. By comparing LEV with OXC, another newer AED, LEV can be considered a useful option as initial monotherapy for patients with newly diagnosed focal epilepsy., (© 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Objective: Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC-induced cADRs are unknown., Methods: A total of 40 patients who experienced OXC-induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed., Results: The HLA-B*40:02 and HLA-DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC-MPE group compared to the OXC-tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced cADRs (HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups., Significance: This study is the first to demonstrate an association of HLA-B*40:02 and HLA-DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

The use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [OR] 4.09, p = 0.025) and the general Korean population (OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG-MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG-MPE group when compared to the LTG-tolerant group (OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Stem cell-based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs-E) in a mouse model of epilepsy., Methods: Human ASCs-E, boiled ASCs-E, or fibroblast-extract (fibroblast-E) was intraperitoneally administrated to C57BL/6 mice 15 min before pilocarpine-induced status epilepticus (SE) or during chronic epileptic stage. Blood-brain barrier (BBB) leakage was evaluated by measuring Evans blue dye extravasation. Spontaneous recurrent seizure (SRS) was investigated by long-term video-electroencephalography (EEG) monitoring. The mice performed elevated plus maze, open-field, light/dark transition, and novel object recognition tasks., Key Findings: Acute application of human ASCs-E before SE led to earlier attenuation of seizure spike activities after treatment with diazepam, reduction of BBB leakage, and inhibition of the development of epilepsy. Human ASCs-E treatment (for 7 days) during the chronic epileptic stage suppressed SRS and reduced abnormal epileptic behavioral phenotypes. However, neither boiled ASCs-E nor fibroblast-E had any effects in the experimental epilepsy model., Significance: Our results demonstrate that human ASCs-E prevents or inhibits epileptogenesis and SRS in mice. They also suggest a stem cell-based, noninvasive therapy for the treatment of epilepsy., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Children who experience complex febrile seizures are at a higher risk of subsequent epileptic episodes, and they may require therapy. This issue can be resolved by interventional studies using molecular targets identified and defined in animal models. In the current study, the molecular changes in the rat brain after febrile seizures were examined throughout the latent period, and erythropoietin was administered as a potentially antiepileptogenic intervention., Methods: The changes in the expressions of genes that were differentially regulated during the latent period after febrile seizures were categorized into the following four patterns: (1) continuously high (CH); (2) continuously low (CL); (3) rise and fall (RF); and (4) going-up (GU). Erythropoietin was administered immediately after seizure cessation and then once daily for at most 7 days, and spontaneous recurrent seizures and cellular and molecular changes were investigated., Key Findings: The CH genes were associated with cell cycle and adhesion, whereas the CL genes were related to energy metabolism. Within the category of RF, the largest changes were for genes involved in inflammation, apoptosis, and γ-aminobutyric acid (GABA) signaling. The GU category included genes involved in ion transport and synaptogenesis. Along with an early rise in inflammatory genes, there were substantial increases in brain edema and activated microglia during the early latent period. Erythropoietin reduced the early inflammatory responses and modulated the molecular alterations after febrile seizures, thereby reducing the risk of subsequent spontaneous seizures., Significance: Erythropoietin treatment may provide a new strategy for preventing epilepsy in susceptible individuals with atypical febrile seizures., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model., Methods: Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography)., Results: The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group., Discussion: Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

Purpose: The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial., Methods: We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology., Results: A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02)., Conclusions: We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS., (Wiley Periodicals, Inc. © 2009 International League Against Epilepsy.)

Purpose: Intracranial electroencephalography (EEG) monitoring is an important process in the presurgical evaluation for epilepsy surgery. The objective of this study was to identify the ideal resection margin in neocortical epilepsy guided by subdural electrodes. For this purpose, we investigated the relationship between the extent of resection guided by subdural electrodes and the outcome of epilepsy surgery., Methods: Intracranial EEG studies were analyzed in 177 consecutive patients who had undergone resective epilepsy surgery. We reviewed various intracranial EEG findings and resection extent. We analyzed the relationships between the surgical outcomes and intracranial EEG factors: the frequency, morphology, and distribution of ictal-onset discharges, the propagation speed, and the time lag between clinical and intracranial ictal onset. We also investigated whether the extent of resection, including the area showing ictal rhythm and various interictal abnormalities--such as frequent interictal spikes, pathologic delta waves, and paroxysmal fast activity--influenced the surgical outcome., Results: Seventy-five patients (42%) were seizure free. A seizure-free outcome was significantly associated with a resection that included the area showing ictal spreading rhythm during the first 3 s or included all the electrodes showing pathologic delta waves or frequent interictal spikes. However, subgroup analysis revealed that the extent of resection did not affect the surgical outcome in lateral temporal lobe epilepsy., Conclusions: The extent of resection is closely associated with surgical outcome, especially in extratemporal lobe epilepsy. Resection that includes the area with total pathologic delta waves and frequent interictal spikes predicts a good surgical outcome.

Purpose: Recent evidence suggests that aberrant neuro/gliogenesis and/or inflammation play critical roles in epileptogenesis. Although the plastic and inflammatory changes have been described in the postseizure hippocampus, little data is available concerning extrahippocampal regions, notably in the piriform and entorhinal cortices, amygdala, and parts of the thalamus. In this study, we examined histological changes in whole epileptic rat brain, with respect to cell death, cell genesis, and inflammation., Methods and Results: Experimental status epilepticus (SE) was induced using a lithium-pilocarpine injection. Neuronal death was evident in the amygdala, piriform, and entorhinal cortices, as well as the subfields of hippocampus. Microglial activation was observed in more extended limbic areas, such as, the hippocampus, entorhinal, perirhinal and piriform cortices, amygdala, thalamus, and hypothalamus, and a robust increase of cell genesis was noted in these damaged areas. The majority of newly generated cells in extrahippocampal areas proliferated in situ, and differentiated mainly into astrocytes or oligodendrocytes. In addition, stromal cell-derived factor-1alpha was found to be induced in close temporal and anatomical association with seizure-induced plasticity., Discussion: These findings indicate that neuronal death, inflammation, and cell genesis are substantially associated throughout the entire brain and that they may influence the epileptogenic process and clinical manifestations.

Purpose: To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible-dosing schedule in Korean patients with refractory partial-onset seizures., Methods: This randomized, double-blind (DB), placebo-controlled trial consists of a 6-week baseline, a 12-week DB treatment, and a 1-week taper phase. Patients having recurrent partial seizures (>or=4 seizures during baseline phase) under adequate pharmacotherapy were recruited to be randomized to PGB or placebo (PLC) in a 2 to 1 ratio. Starting dose was 150 mg/day, increased every 2 weeks by 150-mg/day increments up to maximum dose of 600 mg/day. The primary efficacy parameter was response ratio (RRatio) for all partial seizures., Results: A total of 178 patients (119 in PGB, 59 in PLC) were assigned to the study. Median daily doses of PGB and PLC were 367 and 420 mg/day, respectively. RRatio least squares (LS) mean was -35.8 in the PGB group and -23.2 in the PLC group, with estimated difference in RRatios being -12.6 [95% confidence interval (CI): -22.7 to -2.5, p = 0.015] in the intent-to-treat (ITT) population. Analysis of secondary efficacy measures showed a general trend favoring PGB over PLC. Seventy-seven patients (64.7%) in the PGB group and 18 patients (30.5%) in the PLC group developed adverse events (AEs) related to the study drug. Seven patients (5.9%) in the PGB group discontinued the study prematurely because of AEs. In the post hoc analysis, a significant weight gain (>or=7% of baseline body weight) was found in 24.8% of patients taking PGB, which was more frequent in patients with a lower body mass index (BMI

Purpose: Erythropoietin (EPO) has neuron and astroglial protective effects via reduction of tissue-injuring molecules such as reactive oxygen species, glutamate, inflammatory cytokines, and other damaging molecules. Although EPO may constitute an effective therapeutic modality in cases of epileptic insult, no study has been performed on the effects of exogenous EPO on the chronic seizure formation. In this study, we attempted to investigate if EPO could modulate the altered microenvironment in the epileptic rat brain., Methods: Morphological changes in the hippocampi of rats subjected to lithium-pilocarpine-induced status epilepticus (SE) were examined with respect to neuronal loss, inflammation, blood-brain barrier (BBB) leakage, and cell genesis. Spontaneous recurrent seizures (SRSs) were investigated by long-term video-EEG monitoring., Results: EPO receptor (EPOR) was found to be increased in the hippocampus after SE. Administered EPO prevented, during the latent period following SE, BBB leakage, neuronal death, and microglia activation in the dentate hilus, CA1, and CA3, and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. Moreover, EPO reduced the risk of SRS development., Discussion: These findings suggest that EPO has a potential therapeutic role in the setting of acute epileptic insults.

Purpose: To determine if defects in mitochondrial respiratory chain enzyme complexes (MRCs) contribute to the etiology of childhood epilepsy., Methods: We reviewed the clinical and laboratory features of 48 epileptic patients (23 male, 25 female) with MRC defects that were confirmed by biochemical assays using muscle biopsies., Results: (1) Thirty-five cases (72.9%) were MRC I deficient, one case (2.1%) was MRC II deficient, 11 cases (22.9%) were MRC IV deficient, and one case (2.1%) had combined MRC I and IV deficiencies. (2) In our clinical diagnosis, there were 10 cases (20.8%) with Leigh disease and one case each with myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS) or Alpers' disease (2.1%). Most of the remaining cases (75.0%) had uncategorized mitochondrial cytopathy with nonspecific encephalopathy. (3) For epileptic classification, there were two cases (4.2%) of Ohtahara syndrome, 10 cases (20.8%) of West syndrome, 12 cases (25.0%) of Lennox-Gastaut syndrome, two cases (4.2%) of Landau-Kleffner syndrome, 14 cases (29.2%) of generalized epilepsy, and eight cases (16.7%) of partial epilepsy. (4) The mean age of seizure onset was 2.68 +/- 2.21 (range: 1 month - 5.5 years). (5) Magnetic resonance imaging (MRI) showed diffuse cortical atrophy in 34 cases (70.8%), basal ganglia signal changes in 18 cases (37.5%) and thalamus signal changes in 12 cases (25.0%). (6) A ketogenic diet produced clinical improvements, including seizure reduction and global functional improvement in 75% of 24 patients., Conclusions: MRC defects are one of the important causes of probably symptomatic childhood epilepsy. A ketogenic diet should be carefully considered for treatment of intractable epilepsy related to MRC defects.

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.

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.

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.

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.

Purpose: The usefulness of diffusion tensor magnetic resonance imaging (DT-MRI) is still in debate, and the development of clinically feasible scan protocol is encouraged. The purpose of this study was to investigate the afferent fiber system to the cerebellum in patients with phenytoin (PHT)-induced cerebellar atrophy in comparison with cerebellar atrophy of other etiologies by using DT-MRI., Methods: Thirteen patients (M/F ratio, 7:6; mean age, 42.5 years) and age-matched normal controls (n = 8) participated in this study. The patient group consisted of epilepsy patients who had received PHT therapy (n = 9) and clinically diagnosed as having olivopontocerebellar atrophy (OPCA; n = 4). DT-MRI was performed by using diffusion weighting of b = 600 s/mm2, and fractional anisotropy (FA) and color-coded vector maps were generated. FA of the middle cerebellar peduncle (MCP), the cerebellum, and transverse pontine fibers (TPF) was measured and compared between PHT and OPCA patients., Results: Normal subjects showed FA values of 0.81 +/- 0.07 in MCP, 0.69 +/- 0.04 in TPF, and PHT users showed FA values of 0.84 +/- 0.09 in MCP, 0.72 +/- 0.08 in TPF, and 0.21 +/- 0.04 in cerebellum. OPCA patients showed FA values of 0.39 +/- 0.11 in MCP, 0.46 +/- 0.12 in TPF, and 0.22 +/- 0.07 in cerebellum. PHT users showed a statistically significant reduction of FA only in cerebellum, whereas OPCA demonstrated significant decrease of FA in MCP, TPF, and cerebellum (one-way analysis of variance, p < 0.01). Three-dimensional reconstruction of fiber tracts demonstrated decreased volume and altered fiber integrity within the peduncles and transverse pontine fibers in the OPCA group, whereas fiber course patterns in PHT users were similar to those in controls., Conclusions: PHT users showed normal orientation and anisotropy of MCP and TPF, whereas OPCA demonstrated impaired values, suggesting that PHT directly affects the cerebellum. DT-MRI can demonstrate detailed fiber configurations in degenerative diseases of brainstem and cerebellum and provides insight into the pathomechanisms of cerebellar atrophy.

Purpose: To examine whether the distribution of interictal epileptiform discharges (IEDs) recorded from foramen ovale electrodes (FOEs) correlates with metabolite levels in medial structures of the temporal lobes in patients with mesial temporal lobe epilepsy (MTLE)., Methods: We studied 34 patients with MTLE. The lateralization ratio of IEDs was calculated after counting IEDs recorded from FOEs during prolonged video-EEG monitoring. Metabolite ratio between N-acetylaspartate (NAA) and creatine (Cr) was calculated in each medial temporal structure. The correlation between the lateralization ratio of IEDs and metabolic ratio was evaluated., Results: The asymmetry indexes of IEDs correlated with the asymmetry index of NAA/Cr ratio in the medial temporal structure (rho = -0.380; p = 0.027). Analysis of IEDs and metabolite ratio revealed a significant inverse relation in the contralateral side to the major epileptogenic focus (rho = -0.360; p = 0.037); however, this significance was not present in the ipsilateral side (rho = -0.018; p = 0.921)., Conclusions: There is a correlation between the neuronal dysfunction or damage detected by MRS and the epileptic activity in the contralateral medial temporal structure. Our results suggest that the pathomechanism underlying the contralateral reduction of NAA/Cr ratio, frequently observed in patients with MTLE, might be related to the process of epileptogenesis generating the independent contralateral IEDs.

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

Purpose: We examined diagnostic performances of Tc-99m hexamethylpropylene amine oxime (HMPAO) and Tc-99m electron capture detection (ECD) ictal single-photon emission computed tomography (SPECT) to localize the epileptogenic zones in mesial temporal lobe epilepsy (TLE) and neocortical epilepsy (NE)., Methods: Epileptogenic zones were identified by invasive EEG or surgical outcome. Ictal SPECT was performed with stabilized Tc-99m HMPAO (TLE, 17; NE, 23) and with Tc-99m ECD (TLE, 7; NE, 7). Single-blind visual interpretation was used to localize the epileptogenic zones. Asymmetric index was calculated. Subtraction ictal SPECT was coregistered to a magnetic resonance imaging (MRI) template., Results: In TLE, the sensitivity of Tc-99m HMPAO SPECT was 82% (14 of 17) and that of Tc-99m ECD SPECT was 71% (five of seven). The asymmetric index (AI; 25 +/- 10) of Tc-99m HMPAO SPECT was larger (p = 0.05) than the AI (13 +/- 13) of Tc-99m ECD SPECT in patients with TLE. In NE, the sensitivity of Tc-99m HMPAO SPECT was 70% (16 of 23), but that of Tc-99m ECD SPECT was 29% (two of seven). The AI (15 +/- 10) of Tc-99m HMPAO SPECT was significantly larger (p = 0.02) than the AI (4.8 +/- 6) of Tc-99m ECD SPECT in patients with NE. Subtraction ictal SPECT coregistered to MRI supported the visual assessment., Conclusions: We concluded that the sensitivity of Tc-99m ECD ictal SPECT is similar to that of Tc-99m HMPAO ictal SPECT in TLE; however, ictal hyperperfusion was higher with the Tc-99m HMPAO SPECT. In patients with NE, Tc-99m HMPAO ictal SPECT also was superior to Tc-99m ECD ictal SPECT in sensitivity and degree of hyperperfusion.

Purpose: Application of independent component analysis (ICA) to interictal EEGs and to event-related potentials has helped noise reduction and source localization. However, ICA has not been used for the analysis of ictal EEGs in partial seizures. In this study, we applied ICA to the ictal EEGs of patients with medial temporal lobe epilepsy (TLE) and investigated whether ictal components can be separated and whether they indicate correct lateralization., Methods: Twenty-four EEGs from medial TLE patients were analyzed with the extended ICA algorithm. Among the resultant 20 components in each EEG, we selected components with an ictal nature and reviewed their corresponding topographic maps for the lateralization. We then applied quantitative methods for the verification of increased quality of the reconstructed EEGs., Results: All ictal EEGs were successfully decomposed into one or more ictal components and nonictal components. After EEG reconstruction with exclusion of artifacts, the lateralizing power of the ictal EEG was increased from 75 to 96%., Conclusions: ICA can separate successfully the manifold components of ictal rhythms and can improve EEG quality.

Purpose: Cerebral cortical dysplasia (CD) is one of the important causes of intractable epilepsies and characterized histologically by disorganized cortical lamination and cytomegalic dysplastic neurons. Although it has been suggested that neurotrophins play an important role in differentiation, growth, and survival of developmental neurons, their pathogenetic role in CD has rarely been investigated., Methods: To know the pathogenetic role of various neurotrophins on dysplastic neurons, immunohistochemical staining was performed using antibodies against NGFRp75, trkA, trkB, and trkC in surgical specimens of 20 patients with CD., Results: TrkB and trkC were strongly expressed in dysplastic neurons of severe CD, and NGFRp75 was also expressed in some dysplastic neurons., Conclusions: It is known that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) contribute to the differentiation of neuronal precursor cells, dendritic and axonal arborization, synaptic plasticity, and cellular hyperexcitability, so increased expression of trkB and trkC may have a critical pathogenetic role in cytoskeletal abnormalities and epileptogenicity in dysplastic neurons of CD.

Purpose: To elucidate uncoupling of perfusion and metabolism and its significance in epilepsy, 15O water and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) and Tc-99m hexamethyl-propyleneamine-oxime (HMPAO) single-photon emission computed tomography (SPECT) were examined by SPM (statistical parametric mapping) and quantitation by using SPAM (statistical probabilistic anatomic map)., Methods: [15O]water and [18F]FDG-PET, and [99mTc]-HMPAO SPECT were performed in 25 patients (SPECT in 17 of 25) with medial temporal lobe epilepsy. For volume of interest (VOI) count analysis, the normalized counts using VOI based on SPAM templates of PET and SPECT were compared with those of the normal controls. Perfusion or metabolism was found abnormal if the Z score was >2 for each VOI. For SPM analysis, the differences between each patient's image and a group of normal control images (t statistic for p < 0.01) on a voxel-by-voxel basis were examined to find significant decreases in perfusion or metabolism., Results: With SPAM VOI count analysis, areas of hypoperfusion were found in 13 patients in the epileptogenic temporal lobes by [15O]water PET and areas of hypometabolism in 21 patients by [18F]FDG-PET. With voxel-based SPM analysis, the epileptogenic zones were localized in 15 by [15O]water PET and in 23 patients by [18F]FDG-PET. The localization by [15O]water PET was concordant with that of [18F]FDG-PET. The areas of hypoperfusion on [15O]water PET were absent or smaller than the areas of hypometabolism on [18F]FDG-PET. Interictal [99mTc]-HMPAO SPECT revealed the hypoperfused zones in seven of 17 patients on visual assessment., Conclusions: SPAM VOI count and SPM analysis of [15O]water and [18F]FDG-PET and [99mTc]-HMPAO SPECT revealed that in the same patients, the areas of hypoperfusion were concordant with but smaller than the areas of hypometabolism. Discordance of perfusion and metabolic abnormalities represents an uncoupling of perfusion and metabolism in the epileptogenic zones, and this might explain the lower diagnostic accuracy of perfusion imaging in temporal lobe epilepsy.

Purpose: We investigated whether interictal F-18 fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) or ictal [99mTc]-HMPAO single-photon emission computed tomography (SPECT) was useful to find epileptogenic zones in occipital lobe epilepsy (OLE)., Methods: We reviewed visually and quantified patterns of hypometabolism in interictal [18F]FDG-PET and those of hyperperfusion in ictal SPECT in 17 OLE patients (27 plus minus 6.8 years old; M/F, 10/7; injection time, 30 plus minus 17 s). OLE was diagnosed based on invasive electroencephalography, surgery, and postsurgical outcome (Engel class I in all at an average of 26 months after surgery)., Results: Epileptogenic zones were correctly localized in nine (60%) of 15 patients by interictal [18F]FDG-PET, and asymmetric indices corroborated visual diagnosis. Epileptogenic hemispheres were correctly lateralized in 14 (93%) of 15 patients on [18F]FDG-PET. Epileptogenic hemispheres were correctly lateralized in 13 (76%) of 17 patients using ictal SPECT, but localization was possible in only five (29%) patients. Interictal [18F]FDG-PET was helpful in two of the patients who showed no abnormality on magnetic resonance imaging (MRI) and no possible localization with ictal SPECT., Conclusions: In OLE, ictal SPECT was helpful in lateralization, but less helpful in localization. Interictal [18F]FDG-PET was helpful in localization or lateralization of epileptogenic zones, even in patients with ambiguous MRI or ictal SPECT findings.

Purpose: Our aims were to identify (a) the characteristic magnetic resonance imaging (MRI) findings of cortical dyslamination with cytomegaly, including dysplastic and destructive lesions; (b) the relationship between MRI findings and pathologic characteristics; (c) the diagnostic role of functional neuroimaging studies in patients with these pathologies., Methods: The series consisted of 23 adult patients who had proven cortical dyslamination with cytomegaly. The abnormalities found on MRI were subdivided according to the patterns of involvement. They also were compared with the patients' pathologic characteristics. With visual qualitative analysis, [18F]fluorodeoxyglucose with positron emission tomography (FDG-PET), and ictal single-photon emission computed tomography (SPECT), observations were classified as localizing, lateralizing, nonlateralizing, false-localizing, and false-lateralizing. The standard for correct localization of neuroimages was defined to be the resected lobe., Results: Focal abnormalities were found in 14 cases by MRI. Six cases showed typical MRI findings of focal cortical dysplasia, with focal areas of cortical thickening with or without poor grey-white matter differentiation. Focal subcortical high signal intensities on T2-weighted images occurred in two cases. Six patients had the focal destructive pattern. Three of eight cases with normal MRI and four of eight cases with the nondestructive cortical dysplasia pattern had balloon cells. However, these were not found in six patients with the destructive MRI pattern. FDG-PET localized the pathologic lobe in 13 (65%) of 20 cases, and ictal SPECT achieved this in 11 (61.1%) of 18 cases. FDG-PET and ictal SPECT also correctly localized the pathologic lobe in four and two cases with normal MRI, respectively., Conclusions: Two distinct patterns of abnormal MRI were found in the pathology of cortical dyslamination with cytomegaly. These dysplastic and destructive patterns might reflect different pathogeneses, such as the time of insult. FDG-PET and ictal SPECT have confirmatory and independent diagnostic roles in localizing epileptogenic foci.

Purpose: This study was undertaken to determine what patients with epilepsy need to know about their condition, and to discern what differences exist between patients' perceptions of this need and the medical profession's perception of what patients should know., Methods: Seventy-five consecutive patients with epilepsy and 56 medical personnel (residents and nurses) who were working in either Neurology or Neurosurgery Units were studied using a structured questionnaire consisting of 3 subsets with a total of 27 questions., Results: Using a Likert scale, epilepsy patients gave high priority to their need for more information about "how epilepsy is diagnosed," "the structure of the brain" (p < 0.05, p < 0.01, respectively), and "the diet that might prevent the attack" (p < 0.05) than did medical personnel. Our study also revealed that men were more concerned with questions regarding smoking and drinking than were women (p < 0.05, respectively), whereas married patients gave higher scores in the category of employment (p < 0.01) and contraception/pregnancy (p < 0.05) than did unmarried patients. The patients with one or more seizures per month rated higher scores on questions concerning the first aid at the time of attack and dosage of antiepileptic drugs (AEDs; p < 0.05, respectively) than did the patients with fewer than one seizure per month. The patients taking poly-AED treatment gave higher scores on six items related to AED therapy than did those receiving monotherapy. No significant differences were found with regard to the length of time patients had the condition, nor to educational level or current employment status., Conclusions: An educational program for epilepsy patients should be developed on the basis of understanding that there are differences in perspectives among patients with different sociocultural contexts as well as between patients and medical personnel.

Purpose: Localizable scalp EEGs, during ictal episodes, appear to be rare in neocortical epileptic syndromes. However, studies based on large numbers of patients are also rare. This study aims to identify the characteristic patterns of variable neocortical epilepsies and to evaluate their clinical usefulness in the localization of epileptogenic focuses., Methods: We retrospectively assessed 394 noninvasive ictal recordings from 86 patients who subsequently underwent invasive study and resective surgery. Ictal EEGs were recorded using a video-EEG monitoring system with electrodes placed according to the International 10-20 system, with additional anterior temporal electrodes. The ictal recordings were analyzed according to localizing accuracy and frequency characteristics. The durations of discrete or regional ictal rhythms were also measured., Results: The percentage of discrete or regional EEGs was 23% in frontal lobe epilepsy, 52% in lateral temporal lobe epilepsy, 70% in occipital lobe epilepsy, and 10% in parietal lobe epilepsy. In order of frequency, the localizable ictal rhythms were theta, beta, alpha, delta, and rhythmic spike-and-wave. The duration of discrete or regional ictal rhythms was significantly shorter in frontal lobe epilepsy and parietal lobe epilepsy than in other epilepsies. Ictal beta activity was the most common rhythm in discrete-patterned EEGs. Structural lesions found on MRI did not significantly affect the localization of epileptogenic focuses in the patients. The type of seizure was not related to the degree of localization, with the exception of simple partial seizure., Conclusions: Ictal surface EEG was clinically helpful in the localization of epileptogenic focuses in at least some neocortical epileptic syndromes.

Purpose: To analyze the relationship between ictal electroencephalography (EEG) and ictal single-photon emission computed tomography (SPECT) and to evaluate the diagnostic usefulness of ictal SPECT as an independent presurgical evaluation technique., Methods: Sixty-eight patients with temporal lobe epilepsy who underwent temporal lobectomy with good surgical outcome were included in this study. Ictal SPECT was performed during video-EEG monitoring. The ictal EEG was analyzed in 5-second intervals from the initiation of the ictal rhythm. Lateralized EEG dominance was determined by the amplitude, frequency, or regional patterns of ictal rhythm for each 5-second interval. The total ictal EEG was divided into three periods: preinjection (maximum, 30 seconds), the initial part of the postinjection period (30 seconds), and the latter part of the postinjection period (30 to 60 seconds). The results of ictal SPECT were compared with the lateralized EEG dominance of each period and at seizure onset., Results: Fifty-four of 68 ictal EEGs correctly lateralized seizure focus ipsilateral to the side of surgery. Ictal SPECT correctly lateralized the epileptogenic temporal lobe in 61 of 68 patients (mean injection time, 29.8 seconds from onset). Multivariate analysis indicated that only the EEG dominance of the preejection period correlated significantly with the concordant hyperperfusion of ictal SPECT. Correct lateralization of ictal SPECT occurred in 10 of 14 patients with nonlateralized ictal EEG., Conclusions: Preinjection neuronal activity seems to be important for the accurate interpretation of the hyperperfused patterns of ictal SPECT. Ictal SPECT is an independent and confirmatory presurgical evaluation technique.

Purpose: Although the intracarotid amobarbital procedure (IAP) or Wada test is useful in lateralizing seizure focus in patients with temporal lobe epilepsy (TLE), the results of the IAP memory test are frequently nonlateralizing. An insufficient suppression of the medial temporal region contralateral to the seizure focus may contribute to the failure of lateralization. We tried to correlate IAP memory results with the functional changes in the contralateral medial temporal region as measured by single photon emission computed tomography (SPECT) during IAP., Methods: We performed a (99m)technetium-(Tc) hexamethylene-propylene-amine-oxime (HMPAO) brain SPECT in 19 medial TLE patients during a contralateral IAP (sodium amobarbital injected contralateral to the seizure focus). Regional cerebral blood flow (rCBF) was measured in the contralateral medial temporal region. The amount of decrease in the rCBF was calculated by subtracting the previous measurement from the one obtained with the interictal SPECT., Results: Ten (53%) patients passed and nine (47%) failed the contralateral IAP. The mean percentage decrease in rCBF was 5.3+/-5.3%. There was a significant negative correlation between a decrease in the rCBF and the IAP memory-retention score by Spearman correlation (p = -0.53: p<0.021). Patients with smaller decreases in rCBF (<5%) more frequently passed the contralateral IAP memory test than did those with larger decreases (80 vs. 22%; p<0.023)., Conclusions: We suggest that an insufficient suppression of the contralateral medial temporal function is partly responsible for nonlateralizing IAP memory tests. An IAP-SPECT may be useful in interpreting IAP memory tests for the lateralization of seizure focus in TLE patients.

Purpose: Even though there have been several studies on the prognostic factors of temporal lobe epilepsy (TLE) after lobectomy, no studies have been performed for homogeneous mesial TLE. Furthermore, most studies on the predictors of outcome of epileptic surgery were based on univariate analyses and did not consider modern epileptic surgery investigation modalities such as brain magnetic resonance imaging (MRI) and positron emission tomography (PET). We attempted to identify the prognostic factors in anterior temporal lobectomy (ATL) for mesial TLE with multivariate analysis., Methods: Ninety-three patients with mesial TLE (54 men and 39 women, mean age at surgery, 28.3 +/- 8.2 years) were included in the study. The primary outcome variable was the status of patients in the second postoperative year, classified as either seizure free (except aura), or not seizure free. Clinical, electroencephalographic, MRI, PET, Wada test, and pathological data were considered., Results: Seventy-eight (84.0%) patients had remission of seizures. With univariate analysis, age at surgery (p < 0.001), epilepsy duration before surgery (p = 0.04), and ipsilateral hippocampal sclerosis on MRI (p = 0.02) were found to be significant. By using multivariate analysis, age at surgery (p = 0.001) and ipsilateral hippocampal sclerosis on MRI (p = 0.03) were found to be the most significant prognostic factors., Conclusions: Age at surgery and hippocampal sclerosis are independent prognostic factors for ATL in mesial TLE. These findings suggest that mesial TLE may be a progressive disorder, and surgical outcome is better when early ATL is performed.

Purpose: Because the main blood supply to the medial temporal region is through the posterior cerebral artery, the validity of the intracarotid amobarbital procedure (IAP) is still debated. To verify clinical validity of the IAP, we investigated changes in neuronal function in the medial temporal region during IAP., Methods: Brain single photon emission computed tomography (SPECT) was performed during IAP (IAP-SPECT) in 22 patients with temporal lobe epilepsy (TLE), and regional cerebral blood flow (rCBF) in the medial and lateral temporal regions of interest (ROIs) was measured quantitatively. To determine the distribution of sodium amobarbital, in another 20 patients with TLE, SPECT images were obtained after intracarotid injection of 99mTc-HMPAO mixed with sodium amobarbital., Results: Mean rCBF was 89.2% in the medial temporal region and 81.6% in the lateral temporal region: in the former region, it was significantly lower than that shown by the results of interictal SPECT (99.1%; p < 0.001). In a few patients, however, rCBF did not decrease in the medial temporal region. In only 25% of patients, the medial temporal region was visualized in SPECT images obtained after intracarotid injection of 99mTc-HMPAO., Conclusions: The results in this study demonstrate that IAP is valid because the medial temporal region is inactivated in spite of infrequent delivery of sodium amobarbital. We assume that intratemporal diaschisis is operating for the inactivation of neuronal function. IAP-SPECT with intratemporal ROIs may be useful for monitoring changes in neuronal function in the medial temporal region during IAP.