Magnetoencephalographic detection of synchronized epileptic activity between the hippocampus and insular cortex.

Most magnetoencephalographic signals are derived from synchronized activity in the brain surface cortex. By contrast, the contribution of synchronized activity in the deep brain to magnetoencephalography (MEG) has remained unclear. We compared stereotactic electroencephalography (sEEG) with simultaneous MEG findings in a patient with temporal lobe epilepsy to determine the conditions under which MEG could also detect sEEG findings. The synchrony and similarity of the waves were evaluated using visual inspection and wavelet coherence. A 45-year-old woman with intractable temporal lobe epilepsy underwent sEEG and MEG simultaneously to determine the laterality and precise location of the epileptic focus. When spike-and-waves were seen in the right hippocampal head alone, no distinct spike-and-waves were observed visually in the right temporal MEG. The seizure then spread to the right insula on sEEG with a rhythmic theta frequency while synchronous activity was observed in the right temporal MEG channels. When polyspikes appeared in the right hippocampus, the right temporal MEG showed electrical activity with relatively high similarity to that of the right hippocampal head and insular cortex but less similarity to that of the right lateral temporal lobe cortex. MEG might detect epileptic activity synchronized between the hippocampus and insular cortex.

[Preoperative Simulation in Epilepsy Surgery].

In patients with intractable epilepsy, seizure focus resection can yield favorable seizure outcomes. First, the localization of the seizure focus is estimated by noninvasive methods such as magnetic resonance imaging(MRI), video-electroencephalography(EEG)monitoring, nuclear medicine examinations, magnetoencephalography, and neuropsychological tests. A subgroup of patients may require additional information obtained from the intracranial EEG. There are two major methods for intracranial EEG: intracranial EEG with subdural grid electrodes(SDG)and stereotactic electroencephalography. If the estimated seizure focus overlaps with the eloquent area in noninvasive studies, the margin and extent of the resection are determined by the results of intracranial EEG and functional mapping by electrical cortical stimulation. Herein, we present a case of lobe epilepsy with subtle MRI lesions in the superior temporal sulcus of the language-dominant hemisphere. The results of the SDG and functional mapping showed that the seizure onset zone overlapped with the language area. Resection of the middle and inferior temporal gyri and multiple transections of the language area resulted in Engel IIB seizure outcomes. In such cases, a thorough preoperative simulation is required to determine the best resection margin for seizure control and functional preservation.

Retained Intracerebral Depth Electrode after Stereotactic Electroencephalography Monitoring: A Case Report.

Stereotactic electroencephalography (SEEG) is an increasingly popular surgical modality for localizing the epileptogenic zone. Robot-guided stereotactic electrode placement has been covered in Japan by National Health Insurance since 2020. However, several surgical devices, such as the anchor bolt (a thin, hollow, metal shaft that serves as a guide screw or fixing for each electrode), have not been approved. A 14-year-old female who underwent SEEG for intractable epilepsy and required additional surgery to remove a retained depth electrode from the skull after the SEEG monitoring was finished. She had uncontrolled focal seizures consisting of nausea and laryngeal constriction at the onset. After a comprehensive presurgical evaluation, robot-guided stereotactic electrode implantation was performed to evaluate her seizures by SEEG. Nine depth electrodes were implanted through the twist drill hole. The electrodes were sutured to her skin for fixation without anchor bolts. When we attempted to remove the electrodes after 8 days of SEEG monitoring, one of the electrodes was retained. The retained electrode was removed through an additional skin incision and a small craniectomy under general anesthesia. We confirmed narrowing of the twist drill hole pathway in the internal table of the skull due to osteogenesis, which locked the electrode. This complication might be avoided if an anchor bolt had been used. This case report prompts the approval of the anchor bolts to avoid difficulty in electrode removal. Moreover, approval of a depth electrode with a thinner diameter and more consistent hardness is needed.

Incidence and Prevalence of Epilepsy in Japan: A Retrospective Analysis of Insurance Claims Data of 9,864,278 Insured Persons.

INTRODUCTION: The burden of epilepsy is thought to be high but is difficult to measure. Very few studies in Japan have attempted to estimate prevalence and incidence rates of epilepsy in Japan. METHODS: This retrospective cohort study used commercially collected nationwide insurance claims data from a cohort of 10 million persons between 2012 and 2019 among those aged 0 to 74 years. Using the claims data, cases were identified, and incidence and prevalence rates were estimated. RESULTS: A total of 9,864,278 persons were included. The average age was 34.5 (standard deviation, 18.5) years. A total of 77,312 persons were diagnosed with epilepsy over the 8-year observation period, with a prevalence rate of 6.0 per 1,000 persons with almost no difference by gender. The highest rates were seen among those aged 70-74 years; prevalence rates tended to rise with calendar year (5.4/1,000 in 2012 and 6.0/1,000 in 2019). The incidence rate of epilepsy was 72.1 per 100,000 person-years with slightly higher rates seen among females. Incidence rates were highest at ages less than 12 months (199.8/100,000 person-years), followed by the eldest age group (70-74 years, 179.4/100,000 person-years). CONCLUSION: Understanding the magnitude of disease burden is the basis of determining health policies. In this study, the prevalence and incidence of epilepsy in Japan was shown based on the analysis results of a large-scale general population insurance claims data covering all over Japan.

Intravenous perampanel as an alternative to the oral formulations in Japanese patients with epilepsy.

OBJECTIVE: Perampanel is an oral anti-seizure medication, which is approved in Japan for focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic-clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. METHODS: Study 240 (NCT03754582) was an uncontrolled, open-label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8-12 mg/day of oral perampanel. Patients received 30-minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30-, 60-, or 90-minute) of perampanel 12 mg and a single oral administration of perampanel 12-mg tablet. RESULTS: In Study 240, the transition between 30-minute IV and oral perampanel dosing was associated with a ≤1.4-fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30-minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30- or 60-minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. SIGNIFICANCE: These results support that 30-minute IV perampanel may be a potential short-term alternative to oral formulations for patients with epilepsy.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.

OBJECTIVE: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. METHODS: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. RESULTS: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. CONCLUSIONS: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Primary somatosensory cortex sensitivity may increase upon completion of a motor task.

OBJECTIVES: The electroencephalogram and magnetic field primary somatosensory cortex (S1)-derived components are attenuated before and during motor tasks compared to the resting state, a phenomenon called gating; however, the S1 response after a motor task has not been well studied. We aimed to investigate sensory information processing immediately after motor tasks using magnetoencephalography. MATERIALS AND METHODS: We investigated sensory information processing immediately after finger movement using magnetoencephalography in 14 healthy adults. Volunteers performed a simple reaction task where they were required to press a button when they received a cue. In parallel, electrical stimulation to the right index finger was applied at regular intervals to detect the magnetic brain field changes. The end of the motor task timing was defined using the event-related synchronization (ERS) appearance latency in the brain magnetic field's beta band around the primary motor cortex. The ERS appearance latency and the sensory stimuli timing applied every 500 ms were synchronized over the experimental system timeline. We examined whether there was a difference in the S1 somatosensory evoked field responses between the ERS emergence and ERS disappearance phase, focusing on the N20m-P35m peak-to-peak amplitude (N20m-P35m amplitude) value. A control experiment was also conducted in which only sensory stimulation was applied with no motor task. RESULTS: The N20m-P35m mean amplitude value was significantly higher in the ERS emergence phase (15.81 nAm; standard deviation [SD], 6.54 nAm) than in the ERS disappearance phase (13.54 nAm; SD, 5.12 nAm) (p < 0.05) and the control (12.08 nAm, SD 5.61 nAm) (p = 0.013). No statistically significant differences were identified between the ERS disappearance phase and the control (p = 0.281). CONCLUSIONS: The S1 sensitivity may increase rapidly after exiting from the gating influence in S1 (after completing a motor task).

Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis.

BACKGROUND: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. METHODS: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. RESULTS: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. CONCLUSIONS: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

Magnetoencephalographic spikes with small spikes on simultaneous electroencephalography have high spatial clustering in temporal lobe epilepsy.

OBJECTIVE: To classify magnetoencephalographic (MEG) spikes according to the findings of simultaneous scalp electroencephalography (EEG) to study dipole estimation in patients with temporal lobe epilepsy. METHODS: We analyzed MEG and simultaneous scalp EEG in 27 patients with intractable temporal lobe epilepsy. We classified MEG spikes into three groups (H-EM-spikes, L-EM-spikes, M-spikes) based on the amplitude of simultaneous EEG (50 µV or higher, lower than 50 µV, no spike morphology on EEG, respectively). We calculated parameters of the dipoles, such as goodness of fit (GOF), current moment, and location. RESULTS: We detected 707 MEG spikes, consisting of 175 H-EM-spikes, 245 L-EM-spikes, and 287 M-spikes. Dipoles of H-EM-spikes showed the highest current moment among the three spike groups. Dipoles of L-EM-spikes showed the highest GOF, a moderate current moment, the highest density to cluster, and the highest proportion of being located in the temporal lobe among the three groups. Dipoles of M-spikes showed the lowest GOF and current moment among the three groups. CONCLUSIONS: The characteristics of the dipoles of the MEG spikes differ depending on the simultaneous scalp EEG findings, though most of the MEG spikes were located in the temporal lobe. MEG spikes with concurrent small spikes on simultaneous scalp EEG may have higher spatial clustering in temporal lobe epilepsy.

Hippocampal volumetry to determine the resection side in patients with intractable non-lesional bilateral temporal lobe epilepsy.

Bilateral Temporal lobe epilepsy (BTLE) cases may result in poor surgical outcomes due to the difficulty in determining/localizing the epileptogenic zone. In this study, we investigated whether hippocampal volume (HV) would be useful for the determination of the best resection side in BTLE. Eighteen cases of BTLE determined by a scalp video electroencephalogram (SVEEG) underwent resection via intracranial electroencephalography (IVEEG). Patients with lesions or semiologically determined focus lateralization were excluded. In addition to SVEEG, an epilepsy protocol magnetic resonance imaging (MRI) including hippocampus fluid-attenuated inversion recovery (FLAIR) and HV, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission computed tomography with 123I-iomazenil (IMZ-SPECT), and magnetoencephalography (MEG) were performed for the preoperative evaluation of the lateralization. The resection side was determined based on the IVEEG results, and the seizure outcome at two years postoperatively was classified as either a well-controlled seizure outcome (Engel class I), or residual (classes II-V). We used a Fisher's exact test to compare the concordance between the determination of the epileptic focus by each modality and the resected side where patients achieved a well-controlled seizure outcome. Seizures were well controlled in 9/18 patients after surgery. Eight out of 11 patients (72.7%), in whom the HV results (strongly atrophic side) and the resection side were matched, had well-controlled seizure outcomes (P = 0.0498). The concordance of other presurgical evaluations with the resection side was not significantly related to a well-controlled seizure outcome. HV may be a useful method to determine the optimal resection side of the epileptic focus/foci in cases of suspected BTLE.

[Diagnosis of Epilepsy: Clinical Definition, Seizure Semiology, and Differentiation from Acute Symptomatic Seizure(Provoked Seizure)].

Recently, a practical clinical definition has been proposed by the International League Against Epilepsy(ILAE). Management of an unprovoked first seizure in adults has also been reported with risk factors of recurrence relevant to epilepsy diagnosis by the American Academy of Neurology. The term "unprovoked" implies the absence of a temporary or reversible factor lowering the threshold and producing a seizure at that point in time. A seizure immediately after a stroke or head injury would exemplify a provoked seizure, as called acute symptomatic(or early)seizure, that would not lead to a diagnosis of epilepsy. The underlying mechanisms that cause the early seizure are considered to be different from those of epileptogenesis associated with recurrent epileptic seizures. Psychogenic non-epileptic seizure(PNES)or syncope resembles epileptic seizures and are often misdiagnosed. Some clinical features can help distinguish PNES or syncope from epileptic seizure. Clinicians should be familiarized with seizure semiology presumable to epilepsy. The incidence of epilepsy increases steadily after 50 years of age. As in younger people, the diagnosis of epilepsy is a clinical decision; however, in older people this can be more challenging. Many disorders, common in older people may confuse epilepsy seizures which should be differentiated by appropriate investigations.

Immediate and 6-month seizure outcomes following first and second SARS-CoV2 mRNA vaccinations: A multicenter study with a nationwide survey.

OBJECTIVE: This study aimed to identify seizure outcomes in people with epilepsy (PWE) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) messenger RNA vaccination. METHODS: We examined PWE (n = 332, age ≥ 14 years) treated in four tertiary hospitals between 2021 and 2022 to assess the incidence of seizure worsening following vaccination using closed questions. We identified the clinical factors associated with worsening and 6-month vaccination outcomes. We also conducted a nationwide survey on self-reported seizure worsening using open questions, to which 261 general practitioners from 99 institutes contributed. RESULTS: Of the 282 PWE vaccinated in the four hospitals, 16 (5.7%) exhibited seizure worsening; most of them emerged within 48 h of vaccination and were not sustained. Thus, all PWE were at baseline condition 6 months after their vaccination. PWE with seizure worsening were more significantly associated with focal impaired awareness seizures (p < 0.001), high seizure frequency (p = 0.025), and drug-resistant epilepsy (p = 0.007) at baseline compared to PWE without worsening. Multivariate logistic regression analysis revealed that focal impaired awareness seizures were independently associated with worsening (odds ratio, 7.0; 95% confidence interval, 1.50-32.77). A nationwide survey of 5156 PWE data (real-world data) confirmed an extremely low incidence rate of self-reported seizure worsening (0.43%). SIGNIFICANCE: Some PWE, particularly refractory focal epilepsy, exhibit seizure worsening. However, the worsening events were infrequent, non-sustainable, and probably under-reported by PWE, suggesting that there is little evidence that worsening seizures discourage current and future vaccinations.

Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors.

BACKGROUND: While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. METHODS: A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. RESULTS: During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/µL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). CONCLUSION: Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

Characterization of cortical activity in juvenile myoclonic epilepsy by gradient magnetic field topography.

OBJECTIVE: Gradient magnetic field topography (GMFT) illustrates the magnetic field gradients of epileptic spike or polyspikes (S/PS) activities on a volume-rendered brain surface. The purpose is to characterize cortical activation in juvenile myoclonic epilepsy (JME). METHODS: We compared interictal S/PS activities in 10 patients with JME to five patients with Lennox-Gastaut syndrome (LGS). We defined areas with gradients exceeding 300fT/cm as activated zones (AZs) on GMFT. We defined the hemisphere where an AZ initially appeared as the "preceding hemisphere". We localized the foci where AZs arose and evaluated their spatiotemporal changes. RESULTS: In JME, the localization of S/PS in the preceding hemisphere was frontal in 18 activities (28%), parietal in 10 (15%), and frontal/parietal in 33 (51%), and in the contralateral hemisphere it was frontal in 14 (32%), parietal in 6 (14%), and frontal/parietal in 19 (43%). In LGS, AZs arose in every lobe of the brain. The median interhemispheric time difference was 7 ms (range: 0-20) in JME, which was significantly shorter than the 19 ms (1-50) observed among patients with LGS (p < 0.0001). CONCLUSIONS: AZs are localized within the bilateral frontal and parietal regions. AZs arose serially from foci with small time differences. SIGNIFICANCE: These results are consistent with regional network involvement in JME.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Isolated Neurohypophysial Sarcoidosis Involving the Cavernous Sinus Mimicking a Malignant Tumor.

Because of nonspecific clinical and radiological findings, it is difficult to diagnose isolated neurosarcoidosis without histological examination. Distinguishing neurosarcoidosis from neoplasm, infectious disease, or granulomatous disease can be challenging. In this study, we present a case of a 61-year-old female who presented with unilateral blindness. Magnetic resonance imaging (MRI) revealed a large invasive mass lesion located in the neurohypophysis with homogeneous enhancement after the injection of gadolinium. The lesion involved the bilateral cavernous sinus, which extended along the dura of the skull base with leptomeningeal lesions. Contrast-enhanced computed tomography (CT) and fluorodeoxyglucose positron emission tomography/CT of the entire body showed no other lesions. Biochemical examinations showed no useful data, including angiotensin-converting enzyme, ß-glucan, soluble interleukin-2 receptor, and T-SPOT. Cerebrospinal fluid examination revealed only the elevation of total protein. Under the preoperative diagnosis of a malignant tumor or metastatic tumor, followed by tuberculosis, fungal infection, or granulomatous disease, a biopsy was performed to immediately determine the appropriate therapy, which revealed the histological diagnosis of sarcoidosis. After steroid therapy, the lesions had markedly shrunk as observed on MRI, and the eyesight of the patient's right eye was completely restored. In this case, without a biopsy, discriminating between sarcoidosis and a malignant tumor was difficult. We believe that a prompt histological diagnosis of an invasive isolated neurohypophysial mass lesion involving the bilateral cavernous sinus, which is similar to a malignant tumor, is essential for selecting the appropriate therapy.

Neural Sources of Vagus Nerve Stimulation-Induced Slow Cortical Potentials.

OBJECTIVES: This study investigated neuronal sources of slow cortical potentials (SCPs) evoked during vagus nerve stimulation (VNS) in patients with epilepsy who underwent routine electroencephalography (EEG) after implantation of the device. MATERIALS AND METHODS: We analyzed routine clinical EEG from 24 patients. There were 5 to 26 trains of VNS during EEG. To extract SCPs from the EEG, a high-frequency filter of 0.2 Hz was applied. These EEG epochs were averaged and used for source analyses. The averaged waveforms for each patient and their grand average were subjected to multidipole analysis. Patients with at least 50% seizure frequency reduction were considered responders. Findings from EEG analysis dipole were compared with VNS responses. RESULTS: VNS-induced focal SCPs whose dipoles were estimated to be located in several cortical areas including the medial prefrontal cortex, postcentral gyrus, and insula, with a significantly higher frequency in patients with a good VNS response than in those with a poor response. CONCLUSIONS: This study suggested that some VNS-induced SCPs originating from the so-called vagus afferent network are related to the suppression of epileptic seizures.

Seizure Deterioration with Increased Levetiracetam Blood Concentration during the Postpartum Period in Refractory Temporal Lobe Epilepsy.

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.

A longitudinal seizure outcome following the COVID-19 pandemic in 2020 and 2021: Transient exacerbation or sustainable mitigation.

OBJECTIVE: To study the longitudinal seizure outcomes of people with epilepsy (PWE) following the acute and chronic phases of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Consecutive PWE who were treated at the epilepsy center of Hiroshima University Hospital between 2018 and 2021 were enrolled. We evaluated the incidence of seizure frequency increase or decrease following the pandemic during observational periods in 2020 and 2021. Data between 2018 and 2019 were used as a control set. The sustainability of the altered seizure frequency condition was evaluated throughout the study period. We analyzed the clinical, psychological, and social factors associated with PWE with seizure exacerbation or amelioration. RESULTS: Among the 223 PWE who were evaluated (mean age 37.8 ± 16.3 years), seizure frequency increased for 40 (16.8%) and decreased for 34 (15.2%) after the pandemic began. While seizure exacerbation tended to be a transient episode during 2020, seizure amelioration was likely to maintain excellent status over the observation periods; the sustainability of the altered seizure frequency condition was more prominent for amelioration than exacerbation (p < 0.001). Seizure exacerbation was significantly associated with "no housemate" (odds ratio [OR] 3.37; p = 0.045) and "comorbidity of insomnia" (OR 5.80; p = 0.004). Conversely, "structural abnormality of MRI" (OR 2.57; p = 0.039) and "two-generation householding" (OR 3.70; p = 0.004) were independently associated with seizure amelioration. CONCLUSION: This longitudinal observation confirmed that seizure exacerbation and amelioration emerged during the COVID-19 pandemic. The COVID-19 pandemic has shed light on the stark difference that social support systems can make on outcomes for PWE.

Mechanisms underlying the prokinetic effects of endogenous glucagon-like peptide-1 in the rat proximal colon.

Glucagon-like peptide-1 (GLP-1), a well-known insulin secretagogue, is released from enteroendocrine L cells both luminally and basolaterally to exert different effects. Basolaterally released GLP-1 increases epithelial ion transport by activating CGRP-containing enteric afferent neurons. Although bath-applied GLP-1 reduced the contractility of colonic segments, GLP-1-induced stimulation of afferent neurons could also accelerate peristaltic contractions. Here, the roles of endogenous GLP-1 in regulating colonic peristalsis were investigated using isolated colonic segments. Isolated segments of rat proximal colon were placed in an organ bath, serosally perfused with oxygenated physiological salt solution, and luminally perfused with degassed 0.9% saline. Colonic wall motion was recorded using a video camera and converted into spatiotemporal maps. Intraluminal administration of GLP-1 (100 nM) stimulating the secretion of GLP-1 from L cells increased the frequency of oro-aboral propagating peristaltic contractions. The acceleratory effect of GLP-1 was blocked by luminally applied exendin-3 (9-39) (100 nM), a GLP-1 receptor antagonist. GLP-1-induced acceleration of peristaltic contractions was also prevented by bath-applied BIBN4069 (1 µM), a CGRP receptor antagonist. In colonic segments that had been exposed to bath-applied capsaicin (100 nM) that desensitizes extrinsic afferents, GLP-1 was still capable of exerting its prokinetic effect. Stimulation of endogenous GLP-1 secretion with a luminally applied cocktail of short-chain fatty acids (1 mM) increased the frequency of peristaltic waves in an exendin-3 (9-39)-sensitive manner. Thus, GLP-1 activates CGRP-expressing intrinsic afferents to accelerate peristalsis in the proximal colon. Short-chain fatty acids appear to stimulate endogenous GLP-1 secretion from L cells resulting in the acceleration of colonic peristalsis.NEW & NOTEWORTHY Glucagon-like peptide-1 (GLP-1) activates CGRP-containing intrinsic afferent neurons resulting in the acceleration of colonic peristalsis. Short-chain fatty acids stimulate the secretion of endogenous GLP-1 from L cells that accelerates colonic peristalsis. Thus, besides the well-known humoral insulinotropic action, GLP-1 exerts a local action via the activation of the enteric nervous system to accelerate colonic motility. Such a prokinetic action of GLP-1 could underlie the mechanisms causing diarrhea in patients with type-2 diabetes treated with GLP-1 analogs.