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This study aims to compare directed transfer function (DTF), which is an effective connectivity analysis, derived from scalp EEGs between responder and nonresponder groups implanted with vagus-nerve stimulation (VNS). Twelve patients with drug-resistant epilepsy (six responders and six nonresponders) and ten controls were recruited. A good response to VNS was defined as a reduction of ≥50% in seizure frequency compared with the presurgical baseline. DTF was calculated in five frequency bands (delta, theta, alpha, beta, and broadband) and seven grouped electrode regions (left and right frontal, temporal, parieto-occipital, and midline) in three different states (presurgical, stimulation-on, and stimulation-off states). Responders showed presurgical nodal strength close to the control group in both inflow and outflow, whereas nonresponders exhibited increased inward and outward connectivity measures. Nonresponders also had increased inward and outward connectivity measures in the various brain regions and various frequency bands assessed compared with the control group when the stimulation was on or off. Our study demonstrated that the presurgical DTF profiles of responders were different from those of nonresponders. Moreover, a presurgical normal DTF profile may predict good responsiveness to VNS. [ABSTRACT FROM AUTHOR]

Objective: Focal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data. Methods: We retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD. Results: Finally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD. Conclusion: In this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD. [ABSTRACT FROM AUTHOR]

Background We conducted the study to examine accuracy of the magnetoencephalography (MEG) spike source localization in presurgical evaluation of patients with medically refractory focal epilepsy. Methods Ten consecutive patients with refractory focal epilepsy who were candidates for two-stage surgery with long-term intracranial electroencephalography (ICEEG) monitoring were enrolled. Interictal MEG recordings with simultaneous scalp EEG were obtained within 7 days before the ICEEG electrode implantation. The location of each MEG spike source was quantitatively compared with ICEEG spike foci (focal area of interictal spikes) and ICEEG ictal foci (earliest cortical origin of seizures). Gyral-width concordance and sublobar concordance were also determined for all MEG spike sources. Gyral-width concordance was defined by distance of 15 mm or less between MEG spike sources and ICEEG spike foci or ICEEG ictal foci. Results Visual analyses of the MEG traces of all 10 patients revealed 292 spikes (29.2 ± 24.0 per patient). Spike yield of the MEG was similar to the simultaneously recorded scalp EEG. MEG spike sources were closely located with ICEEG spike foci (distance: 9.3 ± 10.8 mm). Clustered MEG spike sources were even closer to ICEEG spike foci (distance: 7.3 ± 6.4 mm). MEG spike sources, even clustered ones, were less concordant with ICEEG ictal foci and had significant longer distance from ICEEG ictal foci (distance: 21.5 ± 15.6 mm for all sources, 19.7 ± 13.7 mm for clustered sources). Gyral-width concordance rate and sublobar concordance rate were also higher with ICEEG interictal spike foci than with ICEEG ictal foci. On the other hand, 53.4% of interictal spike foci from ICEEG were not detected by interictal MEG recordings. Conclusions MEG spike sources, especially clustered ones, from interictal recording could localize the irritative zone of ICEEG with a high accuracy. However, MEG spike sources have relatively poor correlation with seizure onset zone and lower sensitivity in identifying all irritative zones of ICEEG. This limitation should be considered in the interpretation of MEG results. [ABSTRACT FROM AUTHOR]

Headaches are a neglected entity in patients with epilepsy (PWE), although PWE have a high chance of suffering from seizure-related as well as seizure-unrelated headaches. We aimed to identify the prevalence and characteristics of headaches and investigate the correlation between headaches and affective symptoms in PWE. Consecutive PWE who visited our tertiary outpatient clinic were interviewed about headaches and epilepsy. Affective symptoms were evaluated using the Korean version of the Beck Depression Inventory—II (BDI-II), Beck Anxiety Inventory (BAI), and suicidality portion of the Mini-International Neuropsychiatric Interview. We classified headaches as interictal or seizure-related headaches (SRHs; pre- and postictal). Tension-type headache and migraine were defined based on International Classification of Headache Disorders criteria. From the initial cohort of 177 patients (92 men, mean age: 37.1 years), 73 (41.2%) reported suffering from interictal (N = 34, 19.2%), preictal (N = 3, 1.7%), and postictal (N = 48, 27.1%) headaches. Univariate analysis revealed significantly higher BDI and BAI scores in the headache group. Tension-type headaches were the most frequent, and half of the interictal headaches and most of the SRHs were untreated. Spearman's partial correlation analyses showed that headaches overall were significantly related with depression and anxiety. Interictal headaches were correlated with depression only, and postictal headaches were correlated with depression as well as suicidality, separately. These results show that investigating and controlling headaches may relieve affective symptoms and ultimately improve the quality of life of PWE. [ABSTRACT FROM AUTHOR]

Purpose Although mounting evidence suggests that sleep and epilepsy are reciprocal and seizures influence circadian rhythms, sleep–wake pattern and seizure control have not been widely researched. This study aimed to investigate the association of sleep–wake pattern, sleep quality, and chronotype with seizures in patients with epilepsy (PWE). Methods 160 consecutive PWE (aged 20–49 years, focal epilepsy, FE: generalized epilepsy, GE = 127:33) and 130 age–gender matched healthy controls (HC) were enrolled. All subjects completed a sleep diary for more than 2 weeks, Pittsburgh Sleep Quality Index (PSQI), Epworth sleepiness scale (ESS), and the Morningness–Eveningness questionnaire (MEQ). Detailed seizure history was reviewed for the last 1 year. Key findings Sleep–wake patterns on workdays were different between PWE and HC ( p < 0.001), although PSQI, ESS, and MEQ did not differ. Social jetlag (difference of mid-sleep time between workdays and free days) was more evident in PWE (1.4 h) than HC (0.7 h, p < 0.001). GE showed lower MEQ, later mid-sleep time on both workdays and free days, and larger social jetlag than FE. Higher seizure frequency was positively correlated with higher PSQI and ESS after adjusting for age, gender, and number of antiepileptic drugs ( p < 0.05). PWE with lower MEQ presented worse sleep quality. Significance Contrary to HC, PWE maintained sleep–wake patterns more regularly during workdays and free days. GE patients reported more eveningness-preference; however, their sleep quality was not worse than FE. Although sleep quality may affect seizure frequency, sleep–wake patterns and chronotype were not related to seizures in PWE. [ABSTRACT FROM AUTHOR]

Aims: To estimate the effect of levetiracetam (LEV) on cognitive function and mood status in newly diagnosed epilepsy patients. Methods: Fifty-five drug-naïve epilepsy patients (M:F ratio = 31:24; mean age = 30.9 years) were included. All patients underwent two neuropsychological (NP) tests, one before receiving LEV and then another 12.9 ± 5.0 months after starting LEV monotherapy. We evaluated general cognitive function, verbal/visual attention and memory, linguistic and visuospatial functions, frontal lobe function, and mood status. Repeated-measures regression and generalized estimating equation models were applied to assess the effects of all the confounding variables such as seizure control, average LEV dose, duration of epilepsy, inter-test interval, and subtype of epilepsy syndrome. Results: LEV monotherapy over 1 year revealed significant improvements in the following domains of NP tests with the correction of possible confounding variables: verbal and visual attention, psychomotor speed, mental flexibility, executive function, verbal fluency and word generation. No NP domains showed any significant decrease. Conclusion: Our study suggested that LEV monotherapy had no harmful effect on cognitive function in drug-naïve patients with epilepsy. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Purpose: Antiepileptic drugs (AEDs) may have adverse effects on bone metabolism and bone mineral density (BMD). The aim of this study is to determine the changes of bone metabolism and BMD in epilepsy patients who are undergoing levetiracetam (LEV) monotherapy. Methods: Drug-naïve, sixty-one patients with recent onset epilepsy were recruited (24 female, 37 males; mean age: 31.0±13.1 years) in this study. We measured calcium, phosphate, bone alkaline phosphatase, parathyroid hormone, osteocalcin, insulin-like growth factor (IGF)-1, C-telopeptide, vitamin D3 levels and bone density measurements with DEXA method before and after LEV administration of mean duration 14.16±3.36 months. Rusults: T score in lumbar spine (L1–L4) was significantly increased with the correction of multiple T tests using Bonferroni''s test across LEV monotherapy (p =0.0401). However, no significant change was observed in other parameters for BMD and T score. Repeated measures ANOVA with Bonferroni''s correction of confounders such as sex, age, and treatment duration revealed significant increase in T score in lumbar spine (p =0.0164). The level of average LEV dosage itself did not reveal any significant association with BMD and bone metabolism. Conclusions: We suggest that LEV monotherapy may have no harmful effect on bone strength and metabolism for 1 year. [Copyright &y& Elsevier]

Summary Purpose: Ictal single-photon emission computerized tomography (SPECT) is often nonlocalized in patients with partial epilepsy. We repeated ictal SPECT in patients with partial epilepsy whose first ictal SPECT was nonlocalized. We also performed subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) to test the localizability of ictal SPECT. Methods: We recruited 69 patients with partial epilepsy (33 male and 36 female, mean plus or minus standard deviation age 29.5 ± 12.2 years), who had a repeated ictal SPECT. Ictal-interictal SPECT subtractions were performed, and the subtracted SPECTs were coregistered with their brain MRI studies. SISCOM results were considered to be localizing when the results were concordant with the final location of the epileptic focus, as determined by the presurgical evaluation. We compared seizure duration, tracer injection time, interictal and ictal scalp electroencephalography (EEG) patterns, presence and time of secondary generalization, and epilepsy classification between the localized and nonlocalized SISCOM groups. Key Findings: The SISCOM results of the second ictal SPECT were localized in 43 (62.3%) patients and nonlocalized in 26 (37.7%) patients. In the second ictal SPECT, the radiotracer injection time was significantly shorter in the localized group (25.1 ± 8.9 s), as compared to the nonlocalized group (49.2 ± 55.8 s) (p = 0.008). Furthermore, the radiotracer injection time of the second ictal SPECT was significantly shorter than the first ictal SPECT, only in the localized group (36.8 ± 23.8 s in the first and 25.1 ± 8.9 s in the second ictal SPECT in the localized group, p = 0.004). The percent injection time ([(tracer injection time−seizure onset time)/total seizure duration] × 100%) in the second SPECT was significantly shorter in the localized group, as compared to the nonlocalized group (37.9 ± 23.0% in the localized group and 72.3 ± 46.2% in the nonlocalized group, p < 0.001). The localized ictal EEG patterns at the time of injection were more frequent in the localized SISCOM group. The secondary generalization of seizures at the time of injection was more frequent in nonlocalized groups. Significance: Repeated ictal SPECT with SISCOM analysis is helpful for localizing an epileptic focus in patients with partial epilepsy who have a nonlocalized first ictal SPECT. The most important factor for increasing the localizability of repeated ictal SPECT is early injection time and a localizing ictal EEG pattern at the time of radiotracer injection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the antiepileptic effect of low-frequency rTMS (repetitive transcranial magnetic stimulation) in the patients with intractable epilepsy. Methods: We enrolled 35 patients with localization-related epilepsy who had experienced at least one complex partial seizure or a secondarily generalized seizure per week on a constant antiepileptic drug regimen over an 8-week period. rTMS was administered using a Rapid 2 magnetic stimulator with an air-cooled coil at 0.5Hz for 5 consecutive days at 100% of rMT (resting motor threshold). Patients were divided into a focal stimulation group with a localized epileptic focus, or a non-focal stimulation group with a non-localized or multifocal epileptic focus. These two groups were then randomly subdivided into four subgroups depending on the total number of stimulations administered, i.e., 3000 pulse and 1500 pulse subgroups. Weekly seizure frequencies were determined for 8 weeks before and after rTMS. To compare the number of interictal spikes before and after rTMS, EEG was recorded twice before (1st day) and after rTMS (5th day). Results: Mean weekly seizure frequency was non-significantly decreased after rTMS (8.4→6.8/week, −13.9%). Longer stimulation subgroups (3000 pulses, −23.0%) tended to have fewer seizures than shorter stimulation subgroups (1500 pulses, −3.0%), without statistical significance. TMS stimulation site and structural brain lesions did not influence seizure outcome. However, interictal spikes significantly decreased (−54.9%, P =0.012) after rTMS and they totally disappeared in 6 patients (17.1%, 6/35). Conclusions: Low-frequency rTMS reduced interictal spikes, but its effect on seizure outcome was not significant. Focal stimulation for a longer duration tended to further reduce seizure frequency. Significance: These findings may help clinicians to further investigate the therapeutic potential of the rTMS for patients with intractable epilepsy. [Copyright &y& Elsevier]

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the cognitive effect of levetiracetam (LEV) monotherapy with quantitative electroencephalogram (EEG) analysis and neuropsychological (NP) tests. Methods: Twenty-two drug-naïve epilepsy patients were enrolled. EEG recordings were performed before and after LEV therapy. Relative power of discrete frequency bands was computed, as well as alpha peak frequency (APF) at occipital electrodes. Eighteen patients performed a battery of NP tests twice across LEV treatment. Results: LEV therapy decreased the power of delta (1–3Hz, p <0.01) and theta (3–7Hz, p <0.05) bands and increased that of alpha-2 (10–13Hz, p <0.05) and beta-2 (19–24Hz, p <0.05) bands. Region-specific spectral change was observed: delta power change was significant in fronto-polar region, theta in anterior region, alpha-2 in broad region, and beta-2 in left fronto-central region. APF change was not significant. Improvement in diverse NP tests requiring attention, working memory, language and executive function was observed. Change in theta, alpha-2, and beta-2 power was correlated with improvement in several NP tests. Conclusions: Our data suggest LEV is associated with acceleration of background EEG frequencies and improved cognitive function. Change in frequency band power could predict improvement in several cognitive domains across LEV therapy. Significance: Combined study of quantitative EEG analysis and NP tests can be useful in identifying cognitive effect of antiepileptic drugs. [Copyright &y& Elsevier]

Abstract: We electrically stimulated the face-selective area in epileptic patients while they were performing a face-categorization task. Face categorization was interfered by electrical stimulation but was restored by increasing the visual signal. More importantly, face-categorization interference by electrical stimulation was confined to face-selective electrodes, and the amount of interference was positively correlated with the sensitivity of the face-selective electrodes. These results strongly support the hypothesis that the face-selective area has a direct causal link to face perception. [Copyright &y& Elsevier]

Summary: Ictal Single Proton Emission Computed Tomography (SPECT) has demonstrated high levels of sensitivity in localizing seizures among patients with epilepsy of the mesial temporal lobe (mTLE). However, incorrect information on the lateralization of mTLE has also been reported. In order to investigate the causes of these incorrect localizations, the authors assessed clinical symptoms, as well as the electroencephalography (EEG) and brain SPECT scan data of five patients with mTLE experiencing ictal hyperperfusion of the contralateral temporal lobe. All patients underwent presurgical evaluations, including an interictal and ictal brain SPECT scan. A subtraction ictal SPECT co-registered with Magnetic Resonance Imaging (MRI) procedure or SISCOM was performed. Hyperperfusion (ictal perfusion greater than interictal perfusion) and hypoperfusion (ictal perfusion lower than interictal perfusion), results of SISCOM were analyzed and compared with seizure and ictal EEG pattern patterns. All the five patients had unilateral hippocampal sclerosis, and the radiotracer for the ictal SPECT was injected after the ictal EEG pattern had propagated to the contralateral side. The average delay between the ictal EEG onset and the radiotracer injection was 29.7±9.6s. All hyperperfusion SISCOM results revealed hyperperfusion in the contralateral temporal region with a more intense ictal EEG build-up. However, hypoperfusion SISCOM results demonstrated significant hypoperfusion in the epileptogenic temporal lobe of three of the five patients, but no hypoperfusion finding in the other two patients. This study demonstrates that early ictal EEG pattern propagation to the contralateral side in mTLE may be associated with contralateral ictal hyperperfusion with or without ipsilateral temporal hypoperfusion. The authors recommend simultaneous interpretations of ictal SPECT and ictal EEG propagation patterns at the time of the injection of radiotracers. [Copyright &y& Elsevier]