Effects of Vagus Nerve Stimulation on Sleep-Disordered Breathing, Daytime Sleepiness, and Sleep Quality in Patients With Drug-Resistant Epilepsy

Background@#and Purpose This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) on sleep-disordered breathing (SDB), daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy (DRE). It also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. @*Methods@#Twenty-four patients were recruited. Paired t-tests and multiple linear regression analyses were performed to determine how the demographic and clinical characteristics of the patients influenced the variables that changed significantly after VNS treatment. @*Results@#After VNS, the patients showed significant increases in the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), apnea index, hypopnea index, and oxygen desaturation index (ODI), as well as a significant decrease in the lowest arterial oxygen saturation (SaO 2 nadir) (p<0.05). The multiple linear regression analyses demonstrated that the predictor of larger increases in AHI and RDI was being older at baseline, and that the predictor of a larger increase in apnea index was a longer epilepsy duration. The strongest predictor of a larger increase in ODI was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. The strongest predictor of a larger decrease in SaO2 nadir was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. @*Conclusions@#This study has confirmed that VNS improves seizure control in patients with DRE, whereas it increases obstructive sleep apnea (OSA). Furthermore, the increase in OSA is affected by age and the duration of epilepsy. Therefore, careful observation and monitoring of SDB is recommended in patients who undergo VNS.

Survey on Public Awareness of Neurology in Korea

Background@#Neurology in Korea is a field of clinical practice and research that has been developing for over 30 years, but due to its relatively short history, public awareness is low compared to other clinical fields. The Korean Neurological Association conducted a survey to evaluate the Korean public’s awareness of neurology and the necessity of a name change. This study details the second survey conducted on the topic, with the first being conducted in 2013. The two surveys were compared to identify how the public’s awareness of neurology has improved since 2013 and determine how this can be improved. @*Methods@#The survey was conducted by Gallup Korea, where 1,000 participants were randomly selected and interviewed through telephone surveys. @*Results@#Of the 1,000 participants, 78.5% were familiar with Neurology, similar to the results of the 2013 survey. Meanwhile, when asked about neurological diseases, only 27.9% of the participants recognized neurological diseases correctly. The most accurately recognized symptoms related to Neurology were tremors (57.8%), strokes (55.5%), and dizziness (49.7%). In 2013, 61.7% of the participants thought a name change was necessary. In comparison, only 38.4% responded it needed to change in the recent survey. @*Conclusions@#The preference for Neurology’s current name in Korea has improved since 2013 despite no significant change in the public’s awareness of neurology. More active public relations activities are needed to improve awareness of neurology in the future.

Effect of Long-Term Treatment with Vagus Nerve Stimulation on Mood and Quality of Life in Korean Patients with Drug-Resistant Epilepsy

Background@#and Purpose This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) treatment on suicidality, mood-related symptoms, and quality of life (QOL) in patients with drug-resistant epilepsy (DRE). We also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. @*Methods@#Among 35 epilepsy patients who underwent VNS implantation consecutively in our epilepsy center, 25 patients were recruited to this study for assessing the effects of VNS on suicidality, mood-related symptoms, and QOL. The differences in these variables between before and after VNS treatment were analyzed statistically using paired t-tests. Multiple linear regression analyses were also performed to determine how the patients’ demographic and clinical characteristics influenced the variables that showed statistically significant changes after long-term VNS treatment. @*Results@#After VNS, our patients showed significant improvements not only in the mean seizure frequency but also in suicidality, depression, and QOL. The reduction in depression was associated with the improvement in QOL and more-severe depression at baseline. The reduction in suicidality was associated with higher suicidality at baseline, smaller changes in depression, and less-severe depression at baseline. Improved QOL was associated with lower suicidality at baseline. @*Conclusions@#This study found that VNS decreased the mean seizure frequency in patients with DRE, and also improved their depression, suicidality, and QOL. These results provide further evidence for therapeutic effect of VNS on psychological comorbidities of patients with DRE.

Survey on Public Awareness of Neurology in Korea

Background@#Neurology in Korea is a field of clinical practice and research that has been developing for over 30 years, but due to its relatively short history, public awareness is low compared to other clinical fields. The Korean Neurological Association conducted a survey to evaluate the Korean public’s awareness of neurology and the necessity of a name change. This study details the second survey conducted on the topic, with the first being conducted in 2013. The two surveys were compared to identify how the public’s awareness of neurology has improved since 2013 and determine how this can be improved. @*Methods@#The survey was conducted by Gallup Korea, where 1,000 participants were randomly selected and interviewed through telephone surveys. @*Results@#Of the 1,000 participants, 78.5% were familiar with Neurology, similar to the results of the 2013 survey. Meanwhile, when asked about neurological diseases, only 27.9% of the participants recognized neurological diseases correctly. The most accurately recognized symptoms related to Neurology were tremors (57.8%), strokes (55.5%), and dizziness (49.7%). In 2013, 61.7% of the participants thought a name change was necessary. In comparison, only 38.4% responded it needed to change in the recent survey. @*Conclusions@#The preference for Neurology’s current name in Korea has improved since 2013 despite no significant change in the public’s awareness of neurology. More active public relations activities are needed to improve awareness of neurology in the future.

Effect of Long-Term Treatment with Vagus Nerve Stimulation on Mood and Quality of Life in Korean Patients with Drug-Resistant Epilepsy

Background@#and Purpose This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) treatment on suicidality, mood-related symptoms, and quality of life (QOL) in patients with drug-resistant epilepsy (DRE). We also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. @*Methods@#Among 35 epilepsy patients who underwent VNS implantation consecutively in our epilepsy center, 25 patients were recruited to this study for assessing the effects of VNS on suicidality, mood-related symptoms, and QOL. The differences in these variables between before and after VNS treatment were analyzed statistically using paired t-tests. Multiple linear regression analyses were also performed to determine how the patients’ demographic and clinical characteristics influenced the variables that showed statistically significant changes after long-term VNS treatment. @*Results@#After VNS, our patients showed significant improvements not only in the mean seizure frequency but also in suicidality, depression, and QOL. The reduction in depression was associated with the improvement in QOL and more-severe depression at baseline. The reduction in suicidality was associated with higher suicidality at baseline, smaller changes in depression, and less-severe depression at baseline. Improved QOL was associated with lower suicidality at baseline. @*Conclusions@#This study found that VNS decreased the mean seizure frequency in patients with DRE, and also improved their depression, suicidality, and QOL. These results provide further evidence for therapeutic effect of VNS on psychological comorbidities of patients with DRE.

Test-Retest Reliability of Multiple Sleep Latency Test in Diagnosis of Narcolepsy

Objectives@#The diagnosis of hypersomnia may be changed by the repeated multiple sleep latency test (MSLT). We investigated the long-term reliability of MSLT in the diagnosis of narcolepsy type 1(NT1) and 2 (NT2). @*Methods@#We reviewed the data of patients with NT1 and NT2 who underwent MSLT at least twice between 2008 and 2020. The clinical information and polysomnography/MSLT data were thoroughly assessed, and two sleep experts evaluated the consistency and reliability of diagnosis independently. @*Results@#Eighty patients (38 with NT1 and 42 with NT2 as a final diagnosis) were included in this study. Of the 80 patients, 20 (nine with NT1 and 11 with NT2) underwent the 3rd MSLT. No significant differences were found in the sleep data and Epworth Sleepiness Scale at baseline. During the 2nd MSLT, 18.4% (n=7) patients with NT1 and 47.6% (n=20) patients with NT2 did not satisfy the diagnosis of narcolepsy. At the 3rd MSLT, six out of nine patients with NT1 and seven of 11 patients with NT2 were not suitable for narcolepsy. Two of the initial NT1 (5.2%) and 10 of the initial NT2 (23.8%) patients were found to be normal. Three patients who were confirmed to have NT1 through consecutive MSLTs had significantly shorter sleep latency and more number of sleep-onset rapid eye movements than the other patients. @*Conclusions@#The reliability of MSLT were not robust in the diagnosis of NT1 and NT2 in this long-term follow-up study. The MSLT results should be interpreted with careful consideration based on elaborate preparations.

Test-Retest Reliability of Multiple Sleep Latency Test in Diagnosis of Narcolepsy

Objectives@#The diagnosis of hypersomnia may be changed by the repeated multiple sleep latency test (MSLT). We investigated the long-term reliability of MSLT in the diagnosis of narcolepsy type 1(NT1) and 2 (NT2). @*Methods@#We reviewed the data of patients with NT1 and NT2 who underwent MSLT at least twice between 2008 and 2020. The clinical information and polysomnography/MSLT data were thoroughly assessed, and two sleep experts evaluated the consistency and reliability of diagnosis independently. @*Results@#Eighty patients (38 with NT1 and 42 with NT2 as a final diagnosis) were included in this study. Of the 80 patients, 20 (nine with NT1 and 11 with NT2) underwent the 3rd MSLT. No significant differences were found in the sleep data and Epworth Sleepiness Scale at baseline. During the 2nd MSLT, 18.4% (n=7) patients with NT1 and 47.6% (n=20) patients with NT2 did not satisfy the diagnosis of narcolepsy. At the 3rd MSLT, six out of nine patients with NT1 and seven of 11 patients with NT2 were not suitable for narcolepsy. Two of the initial NT1 (5.2%) and 10 of the initial NT2 (23.8%) patients were found to be normal. Three patients who were confirmed to have NT1 through consecutive MSLTs had significantly shorter sleep latency and more number of sleep-onset rapid eye movements than the other patients. @*Conclusions@#The reliability of MSLT were not robust in the diagnosis of NT1 and NT2 in this long-term follow-up study. The MSLT results should be interpreted with careful consideration based on elaborate preparations.

Hematoma-Related Nonhabitual Seizures during Subdural Electrode Monitoring

No abstract available.

Prevalence of Self-Perceived Snoring and Apnea and Their Association with Daytime Sleepiness in Korean High School Students

BACKGROUND AND PURPOSE: There has been no nationwide population-based study of the prevalence of self-perceived snoring/apnea in Korean adolescents. The purpose of this study was to estimate prevalence of self-perceived snoring/apnea in Korean high-school students and to evaluate their association with daytime sleepiness. METHODS: An online survey was used to investigate 12,672 students at 75 high schools across the 15 nationwide districts of South Korea. The variables were obtained using a self-reported questionnaire. The students answered questions about self-perceived snoring/apnea during the past 30 days. Daytime sleepiness was measured using a validated Korean version of the Epworth Sleepiness Scale, which was modified for adolescents. Covariates were the sex, school grade, frequency of self-perceived snoring/apnea, body mass index, sleep duration during a school day, and subjective perception of sleep duration. RESULTS: The prevalence of self-perceived snoring/apnea was 22.8% (26.4% for males vs. 18.8% for females, p<0.001) and 9.2% (10.5% for males vs. 7.7% for females, p<0.001). Obesity was significantly associated with self-perceived snoring [odds ratio (OR)=2.18, 95% confidence interval (CI)=1.94–2.46] and apnea (OR=1.57, 95% CI=1.33–1.86). Multivariate analysis showed that any frequency of self-perceived snoring/apnea was significantly associated with excessive daytime sleepiness (EDS). The OR of EDS increased significantly with the frequency of snoring and apnea. Female, sleep duration of <5 hours during a school day, and subjective perceptions of insufficient and considerable sleep durations were also significantly associated with EDS. CONCLUSIONS: The prevalence of self-perceived snoring/apnea was significantly higher in students who were male and obese. Students with self-perceived snoring/apnea exhibited more significant EDS and an increased risk of EDS as the frequency of snoring and apnea increased.

Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

BACKGROUND AND PURPOSE: This study aimed to estimate the changes in gray matter volume (GMV) and their hemispheric difference in patients with mesial temporal lobe epilepsy (MTLE) using a voxel-based morphometry (VBM) methodology, and to determine whether GMV changes are correlated with clinical features. METHODS: VBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients. RESULTS: In SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups. CONCLUSIONS: Our study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.

Erratum to: Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

Jeong Sik Kim(a,b*), Dae Lim Koo(c*), Mi-Ri Kang(a), Min Jae Seong(a), Won Gu Lee(a), Eun Yeon Joo(a,b), Sung Tae Kim(d), Dae Won Seo(a,b), Seung Bong Hong(a,b)

Frequency of Depression and Suicidality in Patients with Neurological Disorders: Epilepsy, Parkinson's Disease, and Ischemic Stroke

BACKGROUND: Depression and suicide are common in neurological disorders. However, their reported frequencies have varied widely due to heterogeneities in methodology and assessment timing. We evaluated the frequencies of current depression and suicidality in patients with epilepsy, Parkinson's disease (PD), and ischemic stroke (IS). METHODS: We enrolled patients who visited a tertiary care hospital in Seoul between January and December 2013. All of the patients completed the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D). Any patient with depressive symptoms (defined as a total HADS-D or BDI score of ≥9 or ≥17, respectively) was reassessed with a structured psychiatric interview based on the Mini International Neuropsychiatric Interview Plus 5.0.0 (MINI). RESULTS: In total, 305 patients were recruited, comprising epilepsy (n=92, 30.2%), PD (n=99, 32.4%), and IS (n=114, 37.4%). Depressive symptoms were exhibited by 52 epilepsy patients (56.5%), 56 PD patients (56.6%), and 54 IS patients (47.4%), and these were further evaluated with the aid of the MINI. Seven epilepsy patients were diagnosed as major depressive disorder (MDD), five as dysthymic disorder (DD), and nine as depressive disorder not otherwise specified (DDNOS). Twelve PD patients were diagnosed as MDD, 7 as DD, and 10 as DDNOS. Ten stroke patients were diagnosed as MDD, 7 as DD, and 11 as DDNOS. Most patients with depressive symptoms (91.4%) exhibited suicidality. CONCLUSIONS: Patients with epilepsy, PD, and IS frequently exhibit depression and suicidality. Neurologists should always be concerned about comorbid psychiatric problems when they see patients with neurological disorders.

EEG Source Imaging in Partial Epilepsy in Comparison with Presurgical Evaluation and Magnetoencephalography

BACKGROUND AND PURPOSE: The aim of this study was to determine the usefulness of three-dimensional (3D) scalp EEG source imaging (ESI) in partial epilepsy in comparison with the results of presurgical evaluation, magnetoencephalography (MEG), and electrocorticography (ECoG). METHODS: The epilepsy syndrome of 27 partial epilepsy patients was determined by presurgical evaluations. EEG recordings were made using 70 scalp electrodes, and the 3D coordinates of the electrodes were digitized. ESI images of individual and averaged spikes were analyzed by Curry software with a boundary element method. MEG and ECoG were performed in 23 and 9 patients, respectively. RESULTS: ESI and MEG source imaging (MSI) results were well concordant with the results of presurgical evaluations (in 96.3% and 100% cases for ESI and MSI, respectively) at the lobar level. However, there were no spikes in the MEG recordings of three patients. The ESI results were well concordant with MSI results in 90.0% of cases. Compared to ECoG, the ESI results tended to be localized deeper than the cortex, whereas the MSI results were generally localized on the cortical surface. ESI was well concordant with ECoG in 8 of 9 (88.9%) cases, and MSI was also well concordant with ECoG in 4 of 5 (80.0%) cases. The EEG single dipoles in one patient with mesial temporal lobe epilepsy were tightly clustered with the averaged dipole when a 3 Hz high-pass filter was used. CONCLUSIONS: The ESI results were well concordant with the results of the presurgical evaluation, MSI, and ECoG. The ESI analysis was found to be useful for localizing the seizure focus and is recommended for the presurgical evaluation of intractable epilepsy patients.

Electrophysiological Characteristics of Obstructive Sleep Apnea Syndrome with Insomnia: Polysomnography and Cardiopulmonary Coupling Analysis

OBJECTIVES: To characterize sleep of subjects with obstructive sleep apnea syndrome (OSA) with insomnia compared to OSA without insomnia in terms of polysomnography (PSG) and cardiopulmonary coupling (CPC) analysis. METHODS: Subjects with OSA (apnea-hypopnea index, AHI > or =5 /h, n=200) were enrolled and divided into subjects OSA with insomnia (OSA-I) and subjects with OSA only (OSA-O). OSA-I complained of difficulty falling and/or staying asleep at an initial interview in clinic. We compared demographics including mood states, daytime sleepiness, PSG, and CPC parameters between groups, and performed correlation analyses between PSG and CPC parameters for each group. RESULTS: Female ratio was higher in OSA-I than OSA-O. OSA-I were older and slimmer than OSA-O. OSA-O were much drowsier (Epworth Sleepiness Scale 10.0 vs. 6.8). However, mood states were not different between two groups. OSA-I showed significantly longer sleep latency and lower sleep efficiency than OSA-O. Despite of higher arousal index (AI) and AHI of OSA-O, wakefulness after sleep onset was greater in OSA-I. There was no significant difference of CPC parameters between two groups after adjustment of AHI. In correlation analyses, low frequency coupling and high frequency coupling duration were associated with AHI, AI, and lowest SaO2 in both groups. CONCLUSIONS: OSA-I demonstrated more fragmented sleep architecture and disruptive sleep in spite of lower sleep-disordered breathing related distress than OSA-O. CPC analysis is unable to differentiate sleep patterns of OSA subjects with or without insomnia. It is needed to explore factors causing fragmented sleep architecture and disruptive sleep rather than respiratory disturbances in OSA subjects complaining of insomnia.

Objective Sleep Quality in Subjects with Restless Legs Syndrome versus with Psychophysiological Insomnia: Polysomnography and Cardiopulmonary Coupling Analysis

OBJECTIVES: To compare the sleep quality in the view of polysomnography (PSG) and cardiopulmonary coupling (CPC) analysis in subjects with restless legs syndrome (RLS) versus with psychophysiological insomnia (PPI). METHODS: The PSG data of 109 subjects with RLS and 86 with PPI (apnea-hypopnea index <5 /h) were collected. All subjects reported sleep onset and maintenance insomnia. CPC parameters were obtained using CPC analyzer in RemLogic. Sleep spectrogram by CPC analyses categorized sleep as "stable" [high-frequency coupling (HFC), 0.1-0.4 Hz] and "unstable" [low-frequency coupling (LFC), 0.1-0.01 Hz], independent of sleep stages. We compared PSG and CPC parameters between two groups and performed correlation analyses to find the PSG parameters to affect CPC parameters. RESULTS: In PSG parameters, subjects with PPI showed significantly longer sleep latency (14.2+/-20.06 vs. 27.5+/-34.96, p<0.001), and decreased sleep efficiency (SE, 80.5+/-14.96 vs. 76.5+/-14.45, p=0.009) than RLS. CPC parameters were not significantly different between groups. In both groups HFC was positively correlated with total sleep time and SE and was negatively associated with time of wake after sleep onset in both groups. Meanwhile, very LFC showed the opposite results to HFC with the same PSG parameters. CONCLUSIONS: Although subjects with RLS or PPI present sleep onset and maintenance insomnia, objective sleep quality was worse in PPI than RLS. It suggests that CPC as a factor to differentiate sleep quality between the RLS and the PPI has a limited role.

Absence of HLA-B*1502 and HLA-A*3101 Alleles in 9 Korean Patients With Antiepileptic Drug-Induced Skin Rash: A Preliminary Study

There have been a number of studies about correlations between HLA genotypes in various ethnic groups and occurrence of various cutaneous adverse drug reactions, ranging in intensity from mild to severe, caused by antiepileptic drugs (AEDs). This is the first report analyzing the HLA genotypes of 9 Korean patients with skin rashes induced by various AEDs. The AEDs that induced skin rash were lamotrigine (n=3), carbamazepine (n=3), oxcarbazepine (n=1), phenobarbital (n=1), and phenytoin (n=1). None of the patients' HLA genotypes was either HLA-B*1502 or HLA-A*3101. Based on these series of cases, AED-induced skin rash can occur independently of HLA-B*1502 or HLA-A*3101 genotypes in the Korean patients.

Clinical Efficacy of Incomplete Cognitive Behavior Therapy for Insomnia

BACKGROUND: It is widely accepted that cognitive-behavioral therapy for insomnia (CBT-I) is more effective than pharmacological treatments. However, the lack of trained experts and the duration, intensity, and cost of four individual treatment sessions curtail the widespread use of CBT-I in Korea. The aim of this study was to determine the clinical efficacy in patients who completed four sessions of CBT-I and in those who did not. METHODS: We investigated 81 patients with chronic insomnia (32-82 years old) who participated individual, four-session CBT-I between February 2010 and June 2013. The clinical efficacy was evaluated by estimating of total sleep time (TST), sleep latency (SL), waking after sleep onset (WASO), and sleep efficiency (SE) based on the sleep diaries. RESULTS: Of the 81 patients, 28 (34.6%) completed the four sessions. 22 (27.1%) withdrew after 1st session, 17 (20.9%) dropped after 2nd session, and 8 (9.9%) stopped voluntarily after 3rd session. Six were excluded due to incomplete sleep diaries. Clinical efficacy was measured in patients who completed at least two sessions (n=53, 65.4%); the mean SE improved from 68.8 to 87.6%, and in 40 (75.4%) the SE was normalized (> or =85%). Other parameters (TST, from 321.0 to 351.3 min; SL, from 61.9 to 25.0 min; WASO, from 86.3 to 24.4 min) were all improved after incomplete CBT-I. CONCLUSIONS: Sleep induction and maintenance as well as quality have improved in patients who underwent at least two of the four CBT-I sessions. It needs to develop briefer CBT-I to increase adherence to patients.

Therapeutic Drug Monitoring of Topiramate in Status Epilepticus / 대한간질학회지

PURPOSE: Status epilepticus (SE) is a pathologic state where pharmacokinetic alterations can be more pronounced and more rapid than during the other epileptic states. The consequences of such changes can exert negative influences on the timely adequate treatments for stopping uncontrolled seizures during SE. Topiramte (TPM) is one of new antiepileptic drugs with high efficacy in epilepsy, which can also be effectively used in SE. The aim of this study was to evaluate the pharmacokinetic changes during the SE by an analysis of the therapeutic drug monitoring (TDM) of TPM in patients with SE. METHODS: We retrospectively analyzed 49 serum measurements of TPM from 22 subjects with SE. The serum concentrations of TPM were measured by HPLC-tandem mass spectrometry. TDM data were categorized into malignant status epilepticus (MSE), refractory status epilepticus (RSE), and non-status epilepticus (NSE) groups. We compared concentration-to-dose ratio (CDR) among those groups. RESULTS: Among 49 cases, 11 were in MSE, 19 in RSE, and 19 in NSE. The daily dose of TPM was higher in MSE (median, interquartile range: 600, 600-800 mg) than in RSE (300, 250-600 mg) and NSE (200, 150-400 mg). The daily dose adjusted for body weight was also higher in MSE (12.2, 10.4-13.9 mg/kg) than in RSE (4.5, 3.8-12.2 mg/kg) and NSE (4.1, 2.3-7.1 mg/kg) (p0.1). However, the concentration-to-dose ratio (CDR) was significantly lower in MSE (0.41, 0.35-0.59 kg/L) and RSE (0.85, 0.39-1.23 kg/L) than in NSE (1.72, 0.96-2.24 kg/L) (post hoc analysis, p<0.005, 0.05). CONCLUSIONS: The serum concentrations of TPM can be influenced by SE, particularly in MSE. The higher range of dose of TPM could be needed for an adequate treatment of SE.

Therapeutic Drug Monitoring of Topiramate in Status Epilepticus

PURPOSE: Status epilepticus (SE) is a pathologic state where pharmacokinetic alterations can be more pronounced and more rapid than during the other epileptic states. The consequences of such changes can exert negative influences on the timely adequate treatments for stopping uncontrolled seizures during SE. Topiramte (TPM) is one of new antiepileptic drugs with high efficacy in epilepsy, which can also be effectively used in SE. The aim of this study was to evaluate the pharmacokinetic changes during the SE by an analysis of the therapeutic drug monitoring (TDM) of TPM in patients with SE.METHODS: We retrospectively analyzed 49 serum measurements of TPM from 22 subjects with SE. The serum concentrations of TPM were measured by HPLC-tandem mass spectrometry. TDM data were categorized into malignant status epilepticus (MSE), refractory status epilepticus (RSE), and non-status epilepticus (NSE) groups. We compared concentration-to-dose ratio (CDR) among those groups.RESULTS: Among 49 cases, 11 were in MSE, 19 in RSE, and 19 in NSE. The daily dose of TPM was higher in MSE (median, interquartile range: 600, 600-800 mg) than in RSE (300, 250-600 mg) and NSE (200, 150-400 mg). The daily dose adjusted for body weight was also higher in MSE (12.2, 10.4-13.9 mg/kg) than in RSE (4.5, 3.8-12.2 mg/kg) and NSE (4.1, 2.3-7.1 mg/kg) (p<0.01). Serum concentrations of TPM were less in MSE (5.8, 4.2-7.3 mg/L) and RSE (4.9, 2.9-6.0 mg/L) than in NSE (5.5, 3.3-9.0 mg/L), which were not significantly different among the groups (p>0.1). However, the concentration-to-dose ratio (CDR) was significantly lower in MSE (0.41, 0.35-0.59 kg/L) and RSE (0.85, 0.39-1.23 kg/L) than in NSE (1.72, 0.96-2.24 kg/L) (post hoc analysis, p<0.005, 0.05).CONCLUSIONS: The serum concentrations of TPM can be influenced by SE, particularly in MSE. The higher range of dose of TPM could be needed for an adequate treatment of SE.

Cortico-Cortical Modulation Induced by 1-Hz Repetitive Transcranial Magnetic Stimulation of the Temporal Cortex

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has potential as a noninvasive neuromodulation treatment method for various neuropsychiatric disorders, and repeated sessions of rTMS are more likely to enhance the therapeutic efficacy. This study investigated neurophysiologic and spatiodynamic changes induced by repeated 1-Hz rTMS of the temporal cortex using transcranial magnetic stimulation (TMS) indices and fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twenty-seven healthy subjects underwent daily 1-Hz active or sham rTMS of the right temporal cortex for 5 consecutive days. TMS indices of motor cortical excitability were measured in both hemispheres daily before and after each rTMS session, and 2 weeks after the last stimulation. FDG-PET was performed at baseline and after the 5 days of rTMS sessions. RESULTS: All subjects tolerated all of the sessions well, with only three of them (11.1%) reporting mild transient side effects (i.e., headache, tinnitus, or local irritation). One-Hz rTMS decreased motor evoked potential amplitudes and delayed cortical silent periods in the stimulated hemisphere. Statistical parametric mapping of FDG-PET data revealed a focal reduction of glucose metabolism in the stimulated temporal area and an increase in the bilateral precentral, ipsilateral superior and middle frontal, prefrontal and cingulate gyri. CONCLUSIONS: Repeated rTMS sessions for 5 consecutive days were tolerated in all subjects, with only occasional minor side effects. Focal 1-Hz rTMS of the temporal cortex induces cortico-cortical modulation with widespread functional changes in brain neural networks via long-range neural connections.