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Shigeto Hiroshi Last modified date:2024.06.03



Graduate School
Undergraduate School
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Homepage
https://kyushu-u.elsevierpure.com/en/persons/hiroshi-shigeto
 Reseacher Profiling Tool Kyushu University Pure
https://epilepsy.kyushu-u.ac.jp/
Acting as a representative of the Epilepsy Treatment and Medical Cooperation Council at the Fukuoka Epilepsy Support Hospital(Kyushu University Hospital) .
Academic Degree
Medical doctor, Philosophy of doctor
Country of degree conferring institution (Overseas)
No
Field of Specialization
Neurology, Neurophysiology, Epilepsy
ORCID(Open Researcher and Contributor ID)
0000-0001-5437-943X
Total Priod of education and research career in the foreign country
02years00months
Outline Activities
I am engaged in the study of neurological disease both for clinical and research. Basically, I have been using the method of neurophysiology. For the epilepsy, I have studied the feasibility of the magnetoencephalograpy for detecting the epileptic electrical discharges in patient. I also analysis brain epileptic magnetic activity using network analysis. We analyze the scalp electroencephalogram, stereotactic electroencephalogram and electrocorticogram in order to reveal the influences of sleep, biological rhythm, memory and higher cortical function on the relationship between limbic system and neocortex. I also refer to our previous findings in a rat model with focal cortical dysplasia that produces spontaneous epileptic seizures of hippocampal origin.
Research
Research Interests
  • Detection of epileptic activity biomarkers using machine learning
    keyword : epilepsy, machine learning
    2020.04~2015.03.
  • Detection of microRNAs as biomarker of epileptic seizures
    keyword : epilepsy, microRNA
    2023.04~2028.03.
  • Elucidation of language processing using MEG and DC stimulation
    keyword : Magnetoencephalography
    2021.04~2024.03.
  • Mechanism of accelerating forgetting of epilepsy patients
    keyword : epilepsy memory
    2016.04~2020.04.
  • Investigate the mechanisms of epileptogenesis using animal study and human MEG study
    keyword : spontaneous seizure, rat, MEG
    2012.04~2015.03.
  • Effect of cervical carotid artery cooling on cortical epileptic activity.
    keyword : epilepsy cooling cervical
    2006.04~2007.12We study the cooling effect on cortical epileptic electrical activity by the cooling of cervical carotid artery, which reduced brain temperature indirectly and non-invasively. .
  • Investigate the epileptogenicity of focal cortical dysplasia
    keyword : epilepsy focal cortical dysplasia
    2001.10~2011.04We study about the epileptogenicity of focal cortical dysplasia using freeze lesion rat model..
  • Study the effect of electrical stimulation on the generation and suppression of epileptic activity
    keyword : electrical stimulation epilepsy generation suppression
    2001.10~2011.03We made the rat model producing after discharge on neo-cortex. Using this model, we test the efficacy of electrical stimulation both for preventing and provoking seizures..
Academic Activities
Reports
1. Hiroshi Shigeto, Hippocampal modulation of auditory processing in epilepsy, NEUROLOGY AND CLINICAL NEUROSCIENCE, 10.1111/ncn3.12470, Vol.9, No.1, pp.17-23, 2021.01, The hippocampus is anatomically and functionally connected to other brain regions tightly. Especially in the field of memory research, it has become clear that the connections between the cerebral cortex, thalamus, and hippocampus are regulated via slow-wave rhythms and high-frequency oscillation. In addition, the hippocampus, as a limbic system, is more excitable to inputs than the cerebral cortex and has a reverberant circuit structure, which induces long-lasting neural activity. Because of such characteristics of the hippocampus, it is treated as a key structure in epilepsy. Auditory processing has been shown to be affected by hippocampal activity, and impaired auditory processing function in patients with medial temporal lobe epilepsy has been elucidated using techniques such as cognitive behavior tests and electrophysiological recordings. We recorded the auditory-induced magnetoencephalography of patients with refractory medial temporal lobe epilepsy and examined which hemisphere was more affected. In contrast to previous language studies, we only used simple tone stimulation, by which we could obtain the laterality information regarding epileptic activity and left-right difference. In this article, we reviewed the effects of hippocampal activity on brain function, including the findings of our auditory stimulus-induced magnetic field recordings of medial temporal lobe epilepsy..
2. Medical care of epilepsy faces to brain function
Anytime, medical care of epilepsy faces to brain function. Based on seizure semiology and findings of electroencephalography, we search for the excitable brain region and symptomatogenic zone in order to classify the seizure. Whether patient has impairment of consciousness during seizure is important not only for seizure classification but also patient’s social activity. Antiepileptic drugs are chosen based on epilepsy classification and the cause of epilepsy. Thirty to 40% of epilepsy patients are intractable against medication, which leads to increasing dose of antiepileptic drugs and induces brain dysfunction. As for intractable epilepsy, epilepsy surgery is considered. Best candidate for epilepsy surgery is medial temporal lobe epilepsy. There are memory problems before and after surgery in medial temporal lobe epilepsy. MRI negative neocortical epilepsy fails to poor outcome after epilepsy surgery, especially when the epileptogenic zone is estimated over eloquent area. Epilepsy patients feel difficulty not only from seizure itself. Stigma, brain dysfunction and inadequate therapy lead them to tragic life. To do the best and comprehensive medical care for epilepsy patients is important. This article introduces actual medical care facing to brain function with several epilepsy case presentations..
Papers
1. Yuri Mizuno, Taira Uehara, Yuri Nakamura, Toshiki Okadome, Takahiko Mukaino, Kishin Koh, Yoshihisa Takiyama, Takashi Kanbayashi, Noriko Isobe, Jun-Ichi Kira, Hiroyuki Murai, Hiroshi Shigeto, A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1., Journal of sleep research, 10.1111/jsr.14102, e14102, 2023.11, We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep-onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA-DRB1*15:01-DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1..
2. Tasuku Sato, Ichiro Sakamoto, Ken-ichi Hiasa, Masateru Kawakubo, Ayako Ishikita, Shintaro Umemoto, Min-Jeong Kang, Hiroyuki Sawatari, Akiko Chishaki, Hiroshi Shigeto, Hiroyuki Tsutsui, High-echoic line tracing of transthoracic echocardiography accurately assesses right ventricular enlargement in adult patients with atrial septal defect, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, 10.1007/s10554-022-02712-x, 39, 1, 87-95, 2023.01, Accurate measurement of right ventricular (RV) size using transthoracic echocardiography (TTE) is important for evaluating the severity of congenital heart diseases. The RV end-diastolic area index (RVEDAi) determined using TTE is used to assess RV dilatation; however, the tracing line of the RVEDAi has not been clearly defined by the guidelines. This study aimed to determine the exact tracing method for RVEDAi using TTE. We retrospectively studied 107 patients with atrial septal defects who underwent cardiac magnetic resonance imaging (CMR) and TTE. We measured the RVEDAi according to isoechoic and high-echoic lines, and compared it with the RVEDAi measured using CMR. The isoechoic line was defined as the isoechoic endocardial border of the RV free wall, whereas the high-echoic line was defined as the high-echoic endocardial border of the RV free wall more outside than the isoechoic line. RVEDAi measured using high-echoic line (high-RVEDAi) was more accurately related to RVEDAi measured using CMR than that measured using isoechoic line (iso-RVEDAi). The difference in the high-RVEDAi was 0.3 cm(2)/m(2), and the limit of agreement (LOA) was - 3.7 to 4.3 cm(2)/m(2). With regard to inter-observer variability, high-RVEDAi was superior to iso-RVEDAi. High-RVEDAi had greater agreement with CMR-RVEDAi than with iso-RVEDAi. High-RVEDAi can become the standard measurement of RV size using two-dimensional TTE..
3. Toshiki Okadome, Takahiro Yamaguchi, Takahiko Mukaino, Ayumi Sakata, Katsuya Ogata, Hiroshi Shigeto, Noriko Isobe, Taira Uehara, The effect of interictal epileptic discharges and following spindles on motor sequence learning in epilepsy patients., Frontiers in neurology, 10.3389/fneur.2022.979333, 13, 979333-979333, 2022.11, PURPOSE: Interictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance. MATERIALS AND METHODS: Patients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG. RESULTS: Excluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density. CONCLUSION: We found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy..
4. Takahiko Mukaino, Taira Uehara, Jun Yokohama, Toshiki Okadome, Tomomi Arakawa, Setsu Yokoyama, Ayumi Sakata, Kei-Ichiro Takase, Osamu Togao, Naoki Akamatsu, Hiroshi Shigeto, Noriko Isobe, Jun-Ichi Kira, Atrophy of the hippocampal CA1 subfield relates to long-term forgetting in focal epilepsy., Epilepsia, 10.1111/epi.17378, 63, 10, 2623-2636, 2022.10, OBJECTIVE: The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy. METHODS: We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10 min, and 1 week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses. RESULTS: Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10 min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (β = 7.76; Bonferroni-corrected p = 0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate. SIGNIFICANCE: Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy..
5. Toshiki Okadome, Hajime Takeuchi, Takahiro Yamaguchi, Takahiko Mukaino, Hidenori Ogata, Katsuhisa Masaki, Hiroshi Shigeto, Noriko Isobe, Shadowboxing-induced reflex seizures in a patient with focal epilepsy., Epilepsy & behavior reports, 10.1016/j.ebr.2022.100543, 19, 100543-100543, 2022.04, Exercise-induced reflex seizures are a rare form of reflex seizures that are exclusively induced by a specific type of exercise. Many patients with exercise-induced reflex seizures exhibit drug-resistance, and are therefore advised to avoid the triggering exercise. Here, we describe a focal epilepsy patient with shadowboxing-induced reflex seizures. His semiology included focal aware seizures with speech and behavioral arrest that evolved to head version to the right, preceded by cephalic aura. We identified a specific motion that induced these seizures during shadowboxing using video-electroencephalographic recording, and the patient was able to continue boxing by avoiding this motion. We speculate that a broad brain network may be the pathological substrate of his exercise-induced reflex seizures. Identification of the specific motion that induces exercise-induced reflex seizures is useful for not only understanding the underlying pathophysiology, but also for minimizing the therapeutic restriction of the exercise..
6. Koichi Hagiwara, Takashi Kamada, Satoshi O Suzuki, Ayako Miyoshi, Hideaki Tanaka, Hiroshi Shigeto, Shinji Ohara, Naoki Akamatsu, Stereo-electroencephalography evidence of an eccentrically located seizure-onset zone around a polymorphous low-grade neuroepithelial tumor of the young: illustrative case., Journal of neurosurgery. Case lessons, 10.3171/CASE22106, 3, 17, 2022.04, BACKGROUND: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a newly identified low-grade brain tumor with frequent epileptic presentation. Despite the facilitated use of invasive electroencephalography owing to the growing availability of stereo-electroencephalography (SEEG), intracranial features of tumor-related seizures are still scarcely described. This report provides the first description of SEEG-recorded seizures in PLNTY to provide an insight into its surgical strategy. OBSERVATIONS: Spontaneous clinical seizures were recorded with SEEG in a young adult patient with drug-resistant epilepsy associated with a PLNTY in the left lateral temporal cortex. The seizure onset was characterized by low-voltage fast activity (LVFA) and showed eccentric localization with respect to the tumor: LVFA was localized in the anterior portion of the tumor and spread toward the adjacent polar cortex. The language risks associated with the resection of the posterior temporal cortex could thus be minimized. LESSONS: PLNTY can show a focal and eccentric seizure-onset zone around the tumor. The present findings serve to improve the functional and seizure outcomes using the staged invasive approach in PLNTY..
7. Basical approach of EEG diagnosis for epilepsy and progress in the field.
8. Koichi Hagiwara, Hideaki Tanaka, Ayako Miyoshi, Takashi Kamada, Hiroshi Shigeto, Shinji Ohara, Naoki Akamatsu, Postoperative striatal degeneration: a hitherto unrecognized impact of frontal disconnection surgery for drug-resistant epilepsy. Illustrative cases., Journal of neurosurgery. Case lessons, 10.3171/CASE21644, 3, 9, 2022.02, BACKGROUND: Frontal disconnection surgery is a useful surgical option for patients with frontal epilepsy whose seizure onset zones are exceedingly large and thus are not amenable to conventional resective surgery. While it has the advantage of avoiding sequelae stemming from a large resection cavity, the impact of radical anatomofunctional disconnection of such a vast frontal region is not fully understood. OBSERVATIONS: The authors have identified secondary degeneration in the striatum ipsilateral to the frontal disconnection surgery in two adult patients who had otherwise favorable postoperative outcomes following the surgery. On serial postoperative magnetic resonance imaging, the striatum showed transient restricted diffusion in the caudate head and rostral putamen around several weeks postoperatively and subsequent atrophy in the caudate head. The affected striatal regions (i.e., the anterior portion of the striatum) were congruent with the known fronto-striatal connectivity corresponding to the disconnected frontal regions anterior to the primary and supplementary motor areas. Both patients achieved 1-year seizure freedom without apparent disability related to the surgery. LESSONS: The benign postoperative course despite the marked degenerative changes in the ipsilateral striatum supports the feasibility of the frontal disconnection surgery in otherwise inoperable patients with broad frontal epileptogenicity..
9. Ayumi Sakata, Nobutaka Mukae, Takato Morioka, Shunya Tanaka, Takafumi Shimogawa, Hiroshi Shigeto, Taeko Hotta, Dongchong Kang, Masahiro Mizoguchi, Simultaneous Electroencephalographic and Electocorticographic Recordings of Lateralized Periodic Discharges in Temporal Lobe Epilepsy., Clinical EEG and neuroscience, 10.1177/1550059420972266, 53, 1, 61-69, Online ahead of print, 2022.01, 片側性周期性放電を頭蓋内外で記録して比較した。.
10. Koichi Hagiwara, Toshiki Okadome, Takahiko Mukaino, Taira Uehara, Hideaki Tanaka, Takashi Kamada, Ayako Miyoshi, Naoki Akamatsu, Shinji Ohara, Hiroshi Shigeto, Ictal asystole as a manifestation of pure insular epilepsy., Seizure, 10.1016/j.seizure.2021.06.026, 91, 192-195, 2021.10.
11. Teppei Matsubara, Seppo P Ahlfors, Tatsuya Mima, Koichi Hagiwara, Hiroshi Shigeto, Shozo Tobimatsu, Yoshinobu Goto, Steven Stufflebeam, Bilateral Representation of Sensorimotor Responses in Benign Adult Familial Myoclonus Epilepsy: An MEG Study., Frontiers in neurology, 10.3389/fneur.2021.759866, 12, 759866-759866, 2021.10, Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30-50 ms and 30-100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus..
12. Taira Uehara, Hiroshi Shigeto, Takahiko Mukaino, Jun Yokoyama, Toshiki Okadome, Ryo Yamasaki, Katsuya Ogata, Nobutaka Mukae, Ayumi Sakata, Shozo Tobimatsu, Jun-Ichi Kira, Rapidly spreading seizures arise from large-scale functional brain networks in focal epilepsy., NeuroImage, 10.1016/j.neuroimage.2021.118104, 237, 118104-118104, 2021.08, It remains unclear whether epileptogenic networks in focal epilepsy develop on physiological networks. This work aimed to explore the association between the rapid spread of ictal fast activity (IFA), a proposed biomarker for epileptogenic networks, and the functional connectivity or networks of healthy subjects. We reviewed 45 patients with focal epilepsy who underwent electrocorticographic (ECoG) recordings to identify the patients showing the rapid spread of IFA. IFA power was quantified as normalized beta-gamma band power. Using published resting-state functional magnetic resonance imaging databases, we estimated resting-state functional connectivity of healthy subjects (RSFC-HS) and resting-state networks of healthy subjects (RSNs-HS) at the locations corresponding to the patients' electrodes. We predicted the IFA power of each electrode based on RSFC-HS between electrode locations (RSFC-HS-based prediction) using a recently developed method, termed activity flow mapping. RSNs-HS were identified using seed-based and atlas-based methods. We compared IFA power with RSFC-HS-based prediction or RSNs-HS using non-parametric correlation coefficients. RSFC and seed-based RSNs of each patient (RSFC-PT and seed-based RSNs-PT) were also estimated using interictal ECoG data and compared with IFA power in the same way as RSFC-HS and seed-based RSNs-HS. Spatial autocorrelation-preserving randomization tests were performed for significance testing. Nine patients met the inclusion criteria. None of the patients had reflex seizures. Six patients showed pathological evidence of a structural etiology. In total, we analyzed 49 seizures (2-13 seizures per patient). We observed significant correlations between IFA power and RSFC-HS-based prediction, seed-based RSNs-HS, or atlas-based RSNs-HS in 28 (57.1%), 21 (42.9%), and 28 (57.1%) seizures, respectively. Thirty-two (65.3%) seizures showed a significant correlation with either seed-based or atlas-based RSNs-HS, but this ratio varied across patients: 27 (93.1%) of 29 seizures in six patients correlated with either of them. Among atlas-based RSNs-HS, correlated RSNs-HS with IFA power included the default mode, control, dorsal attention, somatomotor, and temporal-parietal networks. We could not obtain RSFC-PT and RSNs-PT in one patient due to frequent interictal epileptiform discharges. In the remaining eight patients, most of the seizures showed significant correlations between IFA power and RSFC-PT-based prediction or seed-based RSNs-PT. Our study provides evidence that the rapid spread of IFA in focal epilepsy can arise from physiological RSNs. This finding suggests an overlap between epileptogenic and functional networks, which may explain why functional networks in patients with focal epilepsy frequently disrupt..
13. Nobutaka Mukae, Daisuke Kuga, Daisuke Murakami, Noritaka Komune, Yusuke Miyamoto, Takafumi Shimogawa, Ayumi Sakata, Hiroshi Shigeto, Toru Iwaki, Takato Morioka, Masahiro Mizoguchi, Endonasal endoscopic surgery for temporal lobe epilepsy associated with sphenoidal encephalocele., Surgical neurology international, 10.25259/SNI_542_2021, 12, 379-379, 2021.07, Background: Temporal lobe epilepsy (TLE) associated with temporal lobe encephalocele is rare, and the precise epileptogenic mechanisms and surgical strategies for such cases are still unknown. Although the previous studies have reported good seizure outcomes following chronic subdural electrode recording through invasive craniotomy, only few studies have reported successful epilepsy surgery through endoscopic endonasal lesionectomy. Case Description: An 18-year-old man developed generalized convulsions at the age of 15 years. Despite treatment with optimal doses of antiepileptic drugs, episodes of speech and reading difficulties were observed 2-3 times per week. Long-term video electroencephalogram (EEG) revealed ictal activities starting from the left anterior temporal region. Magnetic resonance imaging revealed a temporal lobe encephalocele in the left lateral fossa of the sphenoidal sinus (sphenoidal encephalocele). Through the endoscopic endonasal approach, the tip of the encephalocele was exposed. A depth electrode was inserted into the encephalocele, which showed frequent spikes superimposed with high-frequency oscillations (HFOs) suggesting intrinsic epileptogenicity. The encephalocele was resected 8 mm from the tip. Twelve months postoperatively, the patient had no recurrence of seizures on tapering of the medication. Conclusion: TLE associated with sphenoidal encephalocele could be controlled with endoscopic endonasal lesionectomy, after confirming the high epileptogenicity with analysis of HFOs of intraoperative EEG recorded using an intralesional depth electrode..
14. Shimmura M, Uehara T, Ogata K, Shigeto H, Maeda T, Sakata A, Yamasaki R, Kira JI., Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures., Epilepsy Behav, 10.1016/j.yebeh.2019.05.026., 97, 161-168, 2019.08, 心拍から側頭葉てんかん性活動の側在性を推定できる。.
15. Mitsunori Shimmura, Taira Uehara, Katsuya Ogata, Hiroshi Shigeto, Tomoko Maeda, Ayumi Sakata, Ryo Yamasaki, Jun-Ichi Kira, Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures., Epilepsy & behavior : E&B, 10.1016/j.yebeh.2019.05.026, 97, Pt A, 161-168, 2019.08, OBJECTIVES: The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. METHODS: Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincaré plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. RESULTS: Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. CONCLUSIONS: Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity..
16. Teppei Matsubara, Katsuya Ogata, Naruhito Hironaga, Taira Uehara, Takako Mitsudo, Hiroshi Shigeto, Toshihiko Maekawa, Shozo Tobimatsu, Monaural 40-Hz auditory steady-state magnetic responses can be useful for identifying epileptic focus in mesial temporal lobe epilepsy., Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 10.1016/j.clinph.2018.11.026, 130, 3, 341-351, 2019.03, © 2018 International Federation of Clinical Neurophysiology Objective: Patients with mesial temporal lobe epilepsy (mTLE) often exhibit central auditory processing (CAP) dysfunction. Monaural 40-Hz auditory steady-state magnetic responses (ASSRs) were recorded to explore the pathophysiology of mTLE. Methods: Eighteen left mTLE patients, 11 right mTLE patients and 16 healthy controls (HCs) were examined. Monaural clicks were presented at a rate of 40 Hz. Phase-locking factor (PLF) and power values were analyzed within bilateral Heschl's gyri. Results: Monaural 40-Hz ASSR demonstrated temporal frequency dynamics in both PLF and power data. Symmetrical hemispheric contralaterality was revealed in HCs. However, predominant contralaterality was absent in mTLE patients. Specifically, right mTLE patients exhibited a lack of contralaterality in response to left ear but not right ear stimulation, and vice versa in left mTLE patients. Conclusion: This is the first study to use monaural 40-Hz ASSR with unilateral mTLE patients to clarify the relationship between CAP and epileptic focus. CAP dysfunction was characterized by a lack of contralaterality corresponding to epileptic focus. Significance: Monaural 40-Hz ASSR can provide useful information for localizing epileptic focus in mTLE patients..
17. Teppei Matsubara, Katsuya Ogata, Naruhito Hironaga, Yoshikazu Kikuchi, Taira Uehara, Hiroshi Chatani, Takako Mitsudo, Hiroshi Shigeto, Shozo Tobimatsu, Altered neural synchronization to pure tone stimulation in patients with mesial temporal lobe epilepsy: An MEG study., Epilepsy & behavior : E&B, 10.1016/j.yebeh.2018.08.036, 88, 96-105, 2018.11, OBJECTIVE: Our previous study of monaural auditory evoked magnetic fields (AEFs) demonstrated that hippocampal sclerosis significantly modulated auditory processing in patients with mesial temporal lobe epilepsy (mTLE). However, the small sample size (n = 17) and focus on the M100 response were insufficient to elucidate the lateralization of the epileptic focus. Therefore, we increased the number of patients with mTLE (n = 39) to examine whether neural synchronization induced by monaural pure tone stimulation provides useful diagnostic information about epileptic foci in patients with unilateral mTLE. METHODS: Twenty-five patients with left mTLE, 14 patients with right mTLE, and 32 healthy controls (HCs) were recruited. Auditory stimuli of 500-Hz tone burst were monaurally presented to subjects. The AEF data were analyzed with source estimation of M100 responses in bilateral auditory cortices (ACs). Neural synchronization within ACs and between ACs was evaluated with phase-locking factor (PLF) and phase-locking value (PLV), respectively. Linear discriminant analysis was performed for diagnosis and lateralization of epileptic focus. RESULTS: The M100 amplitude revealed that patients with right mTLE exhibited smaller M100 amplitude than patients with left mTLE and HCs. Interestingly, PLF was able to differentiate the groups with mTLE, with decreased PLFs in the alpha band observed in patients with right mTLE compared with those (PLFs) in patients with left mTLE. Right hemispheric predominance was confirmed in both HCs and patients with left mTLE while patients with right mTLE showed a lack of right hemispheric predominance. Functional connectivity between bilateral ACs (PLV) was reduced in both patients with right and left mTLE compared with that of HCs. The accuracy of diagnosis and lateralization was 80%-90%. CONCLUSION: Auditory cortex subnormal function was more pronounced in patients with right mTLE compared with that in patients with left mTLE as well as HCs. Monaural AEFs can be used to reveal the pathophysiology of mTLE. Overall, our results indicate that altered neural synchronization may provide useful information about possible functional deterioration in patients with unilateral mTLE..
18. Mitsunori Shimmura, Taira Uehara, Kenichiro Yamashita, Hiroshi Shigeto, Ryo Yamasaki, Kinya Ishikawa, Jun-Ichi Kira, Slowed abduction during smooth pursuit eye movement in episodic ataxia type 2 with a novel CACNA1A mutation., Journal of the neurological sciences, 10.1016/j.jns.2017.07.040, 381, 4-6, 2017.10.
19. Yuki Matsushita, Yasunari Sakai, Mitsunori Shimmura, Hiroshi Shigeto, Miki Nishio, Satoshi Akamine, Masafumi Sanefuji, Yoshito Ishizaki, Hiroyuki Torisu, Yusaku Nakabeppu, Akira Suzuki, Hidetoshi Takada, Toshiro Hara, Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice., Scientific reports, 10.1038/srep22991, 6, 22991-22991, 2016.03, Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain..
20. Hiroshi Chatani, Koichi Hagiwara, Naruhito Hironaga, Katsuya Ogata, Hiroshi Shigeto, Takato Morioka, Ayumi Sakata, Kimiaki Hashiguchi, Nobuya Murakami, Taira Uehara, Jun-ichi Kira, Shozo Tobimatsu, Neuromagnetic evidence for hippocampal modulation of auditory processing, NEUROIMAGE, 10.1016/j.neuroimage.2015.09.006, 124, Pt A, 256-266, 2016.01, The hippocampus is well known to be involved in memory, as well as in perceptual processing. To date, the electrophysiological process by which unilateral hippocampal lesions, such as hippocampal sclerosis (HS), modulate the auditory processing remains unknown. Auditory-evoked magnetic fields (AEFs) are valuable for evaluating auditory functions, because M100, a major component of AEFs, originates from auditory areas. Therefore, AEFs of mesial temporal lobe epilepsy (mTLE, n = 17) with unilateral HS were compared with those of healthy (HC, n= 17) and disease controls (n= 9), thereby determining whether AEFs were indicative of hippocampal influences on the auditory processing. Monaural tone-burst stimuli were presented for each side, followed by analysis of M100 and a previously less characterized exogenous component (M400: 300-500 ms). The frequency of acceptable M100 dipoles was significantly decreased in the HS side. Beam-forming-based source localization analysis also showed decreased activity of the auditory area, which corresponded to the inadequately estimated dipoles. M400 was found to be related to the medial temporal structure on the HS side. Volumetric analysis was also performed, focusing on the auditory-related areas (planum temporale, Heschl's gyrus, and superior temporal gyrus), as well as the hippocampus. M100 amplitudes positively correlated with hippocampal and planum temporale volumes in the HC group, whereas they negatively correlated with Heschl's gyrus volume in the mTLE group. Interestingly, significantly enhanced M400 component was observed in the HS side of the mTLE patients. In addition, the M400 component positively correlated with Heschl's gyrus volume and tended to positively correlate with disease duration. M400 was markedly diminished after hippocampal resection. Although volumetric analysis showed decreased hippocampal volume in the HS side, the planum temporale and Heschl's gyrus, the two major sources of M100, were preserved. These results suggested that HS significantly influenced AEFs. Therefore, we concluded that the hippocampus modulates auditory processing differently under normal conditions and in HS. (C) 2015 The Authors. Published by Elsevier Inc..
21. Chikara Yamashita, Hiroshi Shigeto, Norihisa Maeda, Takako Torii, Yasumasa Ohyagi, Jun Ichi Kira, A case of central pontine myelinolysis caused by hypophosphatemia secondary to refeeding syndrome, Case Reports in Neurology, 10.1159/000440711, 7, 3, 196-203, 2015.06, Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM..
22. Koichi Hagiwara, Katsuya Ogata, Tsuyoshi Okamoto, Taira Uehara, Naruhito Hironaga, Hiroshi Shigeto, Jun-ichi Kira, Shozo Tobimatsu, Age-related changes across the primary and secondary somatosensory areas: An analysis of neuromagnetic oscillatory activities, CLINICAL NEUROPHYSIOLOGY, 10.1016/j.clinph.2013.10.005, 125, 5, 1021-1029, 2014.05, Objective: Age-related changes are well documented in the primary somatosensory cortex (SI). Based on previous somatosensory evoked potential studies, the amplitude of N20 typically increases with age probably due to cortical disinhibition. However, less is known about age-related change in the secondary somatosensory cortex (SII). The current study quantified age-related changes across SI and SII mainly based on oscillatory activity indices measured with magnetoencephalography.
Methods: We recorded somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation in healthy young and old subjects and assessed major SEF components. Then, we evaluated the phase-locking factor (PLF) for local field synchrony on neural oscillations and the weighted phase-lag index (wPLI) for cortico-cortical synchrony between SI and SII.
Results: PLF was significantly increased in SI along with the increased amplitude of N20m in the old subjects. PLF was also increased in SII associated with a shortened peak latency of SEFs. wPLI analysis revealed the increased coherent activity between SI and SII.
Conclusions: Our results suggest that the functional coupling between SI and SII is influenced by the cortical disinhibition due to normal aging. Significance: We provide the first electrophysiological evidence for age-related changes in oscillatory neural activities across the somatosensory areas. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved..
23. [Electroencephalography for patient with epilepsy].
Electroencephalography (EEG) is the primary means by which epileptic activity in the brain is measured. The frequency of epileptic discharges is influenced by vigilance and biological rhythms. When checking for epileptic activity using EEG, measurements must be repeated and recordings made during sleep are recommended if epileptic discharges do not readily appear. Epileptic discharges must be classified as generalized or focal discharges, and discriminated from non-epileptic discharges such as vertex sharp transients, positive occipital sharp transients, 14 & 6 positive spike discharge, and artifacts. Attention should be paid to small sharp spikes, 6Hz spike and slow wave, focal slow waves, and generalized rhythmic slow waves, which should all be considered variants of epileptic activity. EEG provides information regarding focal and generalized brain dysfunction in addition to epileptic activity. Because the misreading of EEG may negatively affect the lives of patients, reading the EEG correctly is quite important..
24. [Spontaneous seizures in a rat models of multiple prenatal lesioning].
Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Eleven of 16 rats showed spontaneous seizures arising in the hippocampus from postnatal day47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. Alterations in the levels of glutamatergic and GABA-ergic receptors were investigated during growth. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. This model should enable better clarification of the mechanisms underlying the development of human epilepsy..
25. Chikara Yamashita, Hiroshi Shigeto, Norihisa Maeda, Minako Kawaguchi, Mitsue Uryu, Satoru Motomura, Jun-ichi Kira, Transient interhemispheric disconnection in a case of insulinoma-induced hypoglycemic encephalopathy., Journal of the neurological sciences, 10.1016/j.jns.2013.09.025, 335, 1-2, 233-7, 2013.12, We report a case of a 22-year-old male who was transferred to our hospital in a comatose state following successive seizures. Low blood glucose had been detected upon his arrival at the previous hospital. He became responsive 12 days after the onset of coma. Upon regaining consciousness he exhibited severe dysarthria and several interhemispheric disconnection signs such as intermanual conflict, left-hand dysgraphia, left hemispatial neglect confined to the right hand, impaired interhemispheric transfer, and unilateral constructional apraxia of the right hand. Brain MRI disclosed T2-weighted and diffusion-weighted hyperintense lesions with reduced apparent diffusion coefficients in the bilateral centrum semiovale, splenium of the corpus callosum, right posterior limb of the internal capsule, and bilateral middle cerebellar peduncles. As the MRI findings vanished, his interhemispheric disconnection signs gradually resolved. Abdominal imaging studies revealed a pancreatic tumor, which was later endocrinologically diagnosed as an insulinoma. This is an extremely rare report of interhemispheric disconnection signs due to hypoglycemic encephalopathy. The lesions in the bilateral centrum semiovale likely contributed to the interhemispheric disconnection signs..
26. Yuji Kanamori, Hiroshi Shigeto, Naruhito Hironaga, Koichi Hagiwara, Taira Uehara, Hiroshi Chatani, Ayumi Sakata, Kimiaki Hashiguchi, Takato Morioka, Shozo Tobimatsu, Jun-Ichi Kira, Minimum norm estimates in MEG can delineate the onset of interictal epileptic discharges: A comparison with ECoG findings., NeuroImage. Clinical, 10.1016/j.nicl.2013.04.008, 2, 663-9, 2013.11, The analysis of epileptic discharges in magnetoencephalography with minimum norm estimates (MNE) is expected to provide more precise localization of epileptic discharges compared with electroencephalographic estimations. However, the clinical feasibility of MNE remains unclear. In this study, we aimed to elucidate the onset and propagation patterns of interictal spikes using MNE. Seven patients with intractable epilepsy whose epileptogenicity was assumed to exist in the convexity of the cerebral cortex were studied. For MNE and electrocorticography (ECoG), we characterized the propagation patterns of interictal epileptic discharges according to the area in which they originated and where they extended; we then examined whether the propagation patterns observed in MNE were identified by ECoG. We also examined the relationship between the positions of spikes estimated by the equivalent current dipole (ECD) method and MNE. Among the seven patients, nine propagation patterns of epileptic discharges were observed by MNE, all of which were also identified by ECoG. In seven patterns, the epileptic activity propagated around the initial portion. However, in two patterns, the center of activities moved according to propagation with maintained activity of the initial portion. The locations of spikes identified by the ECD method were within the areas estimated by MNE when the epileptic activity propagated. However, the ECD method failed to detect onset activities identified by MNE in three of nine patterns. Thus, MNE is more useful as a means of presurgical evaluation for epilepsy than the ECD method because it can delineate the onset of epileptic activities as shown in ECoG..
27. Hiroshi Shigeto, 鎌田 崇嗣, Spontaneous seizures in a rat model of multiple prenatal freeze lesioning, Epilepsy Res., 10.1016/j.eplepsyres.2013.03.003, 105, 3, 280-291, 2013.08, Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic receptors were investigated during growth. This model should enable better clarification of the mechanisms underlying the development of human epilepsy..
28. Noriko Yutsudo, Takashi Kamada, Kosuke Kajitani, Hiroko Nomaru, Atsuhisa Katogi, Yoko H. Ohnishi, Yoshinori N. Ohnishi, Kei Ichiro Takase, Sakumi Kunihiko, Hiroshi Shigeto, Yusaku Nakabeppu, Erratum FosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior (Neuropsychopharmacology (2013) 38 (1374-1375) DOI: 10.1038/npp.2013.56), Neuropsychopharmacology, 10.1038/npp.2013.56, 38, 7, 1374-1375, 2013.06.
29. Noriko Yutsudo, Takashi Kamada, Kosuke Kajitani, Hiroko Nomaru, Atsuhisa Katogi, Yoko H Ohnishi, Yoshinori N Ohnishi, Kei-ichiro Takase, Kunihiko Sakumi, Hiroshi Shigeto, Yusaku Nakabeppu, fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior., Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 10.1038/npp.2012.260, 38, 5, 895-906, 2013.04, Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of fosB, an immediate early gene encoding FosB and ΔFosB/Δ2ΔFosB by alternative splicing and translation initiation, is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus, following transient forebrain ischemia in the rat brain. Moreover, adenovirus-mediated expression of fosB gene products can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive behavior, suggesting impaired neurogenesis in fosB-null mice. In the current study, we analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosB(d/d) mice that express ΔFosB/Δ2ΔFosB but not FosB, in comparison with wild-type mice, alongside neuropathology, behaviors, and gene expression profiles. fosB-null but not fosB(d/d) mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression, and epilepsy were altered in the hippocampus of fosB-null mice. Thus, we conclude that the fosB-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB..
30. Yuji Kanamori, Hiroshi Shigeto, Minimum norm estimates in MEG can delineate the onset of interictal epileptic discharges: A comparison with ECoG findings, Neuroimage Clin., 2013.04.
31. Hiroshi Shigeto, Atthaporn Boongird, Kenneth Baker, Christoph Kellinghaus, Imad Najm, Hans Lüders, Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat., Epilepsy research, 10.1016/j.eplepsyres.2012.10.002, 104, 1-2, 17-25, 2013.03, Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs..
32. Noriko Isobe, Hiroshi Shigeto, Jun-ichi Kira, First diagnostic criteria for atopic myelitis with special reference to discrimination from myelitis-onset multiple sclerosis., J Neurol Sci., 10.1016/j.jns.2012.02.007, 316, 1-2, 30-35, 2012.05, OBJECTIVE: To establish the first evidence-based diagnostic criteria for atopic myelitis (AM) enabling it to be discriminated from myelitis-onset multiple sclerosis (MS), which is a difficult differential diagnosis. METHODS: Sixty-nine consecutive AM patients examined from 1996 to 2010 at Kyushu University hospital, who fulfilled the empirical definition of AM (2003), and 51 myelitis-onset MS patients in whom allergen-specific IgE was measured, were enrolled. The first available brain MRI findings were compared between the two. Then, we compared the clinical and laboratory features between the 16 AM cases who did not meet the Barkhof brain MRI criteria for MS after more than 5 years follow-up and 51 myelitis-onset MS cases. Based on the discriminative findings, we established diagnostic criteria for AM and calculated the sensitivity and specificity. RESULTS: AM patients had a significantly lower frequency of Barkhof brain lesions on baseline MRI than myelitis-onset MS patients. AM patients had a significantly higher frequency of present and/or past history of atopic disease and hyperIgEemia, and higher cerebrospinal fluid levels of interleukin 9 and CCL11/eotaxin, but a lower frequency of oligoclonal IgG bands than myelitis-onset MS patients. Our proposed diagnostic criteria for AM demonstrated 93.3% sensitivity and 93.3% specificity for AM against myelitis-onset MS, with 82.4% positive predictive value and 97.7% negative predictive value. CONCLUSION: Our first evidence-based criteria for AM show high sensitivity and specificity, and would be useful clinically..
33. Tomonori Iwata, Hiroshi Shigeto, Katsuya Ogata, Ko-ichi Hagiwara, Yuji Kanamori, Taira Uehara, Yasumasa Ohyagi, Shozo Tobimatsu, Jun-ichi Kira, Hyperexcitability restricted to the lower limb motor system in a patient with stiff-leg syndrome., Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 10.1016/j.jocn.2011.03.021, 18, 12, 1720-2, 2011.12, We report a 29-year-old man who presented with a 2-year history of progressive stiffness and painful spasms limited to the bilateral lower limbs, exaggerated by auditory and tactile stimuli. His deep tendon reflexes were slightly increased in both lower extremities. His plantar response was flexor. His serum and cerebrospinal fluid were negative for anti-glutamic acid decarboxylase antibodies. Electromyography of antagonist muscle pairs in his distal lower limbs revealed a failure of reciprocal inhibition. We used transcranial magnetic stimulation with a paired-pulse paradigm, delivered to the cortical area of the upper and lower limbs, and revealed significantly enhanced facilitation only in the area of his lower limbs, but not that representing his upper limbs. His symptoms were improved substantially by 20mg/day of oral diazepam. To our knowledge this is the first report of a patient with hyperexcitability limited to the lower limb motor system in a patient with stiff-leg syndrome..
34. Noriko Yutsudo, Takashi Kamada, Hiroko Nomaru, Yoko H. Ohnishi, Yoshinori N. Ohnishi, Kosuke Kajitani, Kunihiko Sakumi, Hiroshi Shigeto, Yusaku Nakabeppu, Delta FosB and/or Delta 2 Delta FosB regulate proliferation of adult hippocampal neural progenitor cells and suppress spontaneous epileptic seizures, NEUROSCIENCE RESEARCH, 10.1016/j.neures.2011.07.1289, 71, E295-E295, 2011.11.
35. [Epilepsy practice for neurologists].
Epilepsy is a common disease with a high incidence of about one percent. Knowledge of seizure semiology and correct reading of EEG findings are important for diagnosis of epilepsy. Because the primary therapy for epilepsy is antiepileptic drugs (AEDs), including several ones that are newly permitted in Japan, we need to prescribe them based on an understanding of their actions and interaction mechanisms. However, we also need to consider early surgical treatment for temporal lobe epilepsy with hippocampal sclerosis. In the therapeutic decision for adult epilepsy patients many factors such as employment, marriage, child bearing, and co-existent disease need to be considered. The present review provides an overview of the basis of epilepsy practice for neurologists treating adults with epilepsy, including a discussion of new AEDs, epilepsy surgery, women with epilepsy, and epilepsy in the elderly..
36. [Primary care of epilepsy and recent topics]..
37. A late-onset case of nonconvulsive status epilepticus of generalized epilepsy
We report a 78-year-old woman who had episodes of nonconvulsive status epilepticus (NCSE) with dizziness. At 75 years of age, she had first seizure, but was not well examined. At 78 years of age, she had brief myoclonic jerks of her arms, soon after awakening, in May. She suffered from strong dizziness and was admitted in our hospital at the end of June. The symptoms regressed with bed rest in few days and she was discharged. However, she was admitted again with dizziness in the middle of July. There were no myoclonic jerks of her arms or legs and she could converse and interact normally, but was slightly disoriented (JCS: 2). Blood test, Cerebrospinal fluid analyses and brain MRI were normal. An EEG showed frequent intermittent generalized multiple spikes and slow wave complexes and a 3-4Hz generalized spike and slow wave complexes every 2-4 seconds during whole 20 minutes record. Intravenous injection of 5mg diazepam terminated status immediately. Thereafter, she was treated with sodium valproate (400mg/day). Her symptoms improved, and interictal epileptic discharges extremely decreased. Late-onset NCSE of generalized epilepsy is rare. We discussed this case as an important case for diagnosis of NCSE with subtle symptom of dizziness.
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38. Madoka Noriuchi, Yoshiaki Kikuchi, Takashi Yoshiura, Ryutaro Kira, Hiroshi Shigeto, Toshiro Hara, Shozo Tobimatsu, Yoko Kamio, Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder, BRAIN RESEARCH, 10.1016/j.brainres.2010.09.051, 1362, 141-149, 2010.11, Individuals with autism spectrum disorder (ASD) have severe difficulties in social interaction and communication, as well as restricted and/or stereotyped patterns of behavior. Previous studies have suggested that abnormal neural connectivity might be associated with higher information processing dysfunction involving social impairment. However, the white matter structure in ASD is poorly understood. To explore this, we conducted a voxel-based, whole-brain diffusion tensor imaging (DTI) analysis to determine fractional anisotropy (FA), lambda(1), lambda(2) and lambda(3) in high-functioning children with ASD compared with age-, gender-, and handedness-matched healthy control participants. We then investigated whether DTI parameters were associated with behaviorally measured social function. We found that FA and lambda(1) were significantly lower in the ASD group than in the control group in the white matter around left dorsolateral prefrontal cortex (DLPFC), posterior superior temporal sulcus/temporo-parietal junction, right temporal pole, amygdala, superior longitudinal fasciculus, occipitofrontal fasciculus, mid- and left anterior corpus callosum, and mid- and right anterior cingulate cortex. The FA value in the left DLPFC was negatively correlated with the degree of social impairment in children with ASD. Higher values were observed in the cerebellar vermis lobules in the ASD group. The white matter alterations in children with ASD were around cortical regions that play important roles in social cognition and information integration. These DTI results and their relationship to social impairment add to evidence of cerebral and cerebellar white matter structural abnormalities in ASD. (C) 2010 Elsevier B.V. All rights reserved..
39. Yutsudo Noriko, Kamada Takashi, Honda-Ohnishi Yoko, Ohnishi Yoshinori, Kajitani Kosuke, Sakumi Kunihiko, Shigeto Hiroshi, Nakabeppu Yusaku, fosB-null mice exhibit impaired adult hippocampal neurogenesis and spontaneous epileptic seizures, NEUROSCIENCE RESEARCH, 10.1016/j.neures.2010.07.1859, 68, E419-E419, 2010.10.
40. Koichi Hagiwara, Tsuyoshi Okamoto, Hiroshi Shigeto, Katsuya Ogata, Yuko Somehara, Takuya Matsushita, Jun-ichi Kira, Shozo Tobimatsu, Oscillatory gamma synchronization binds the primary and secondary somatosensory areas in humans, NEUROIMAGE, 10.1016/j.neuroimage.2010.02.001, 51, 1, 412-420, 2010.05, Induced gamma activity has a key role in the temporal binding of distributed cortico-cortical processing. To elucidate the neural synchronization in the early-stage somatosensory processing, we studied the functional connectivity between the primary and secondary somatosensory cortices (SI and 511) in healthy subjects using magnetoencephalography (MEG) with excellent spatiotemporal resolution. First, somatosensory-evoked magnetic fields were recorded to determine the locations of each cortical activity. Then we analyzed the phase-locking values (PLVs) of the induced gamma activity to assess neural synchrony within the somatosensory cortical network. We also assessed PLVs in patients with multiple sclerosis (MS) to validate our PLV analysis in evaluating the inter-areal functional connectivity, which can often be impaired in MS. The PLVs of the induced gamma activity were calculated for each pair of unaveraged MEG signals that represented the activities of the contralateral SI and bilateral SII areas. Analysis of PLVs between the SI and SII areas showed significantly increased PLVs for gamma-band activities, starting at an early post-stimulus stage in normal controls, whereas this increase in PLVs was apparently diminished in MS. The PLV analysis provided evidence for early-latency, gamma-band neuronal synchronization between the SI and SII areas in normal controls. Our study first demonstrates the gamma-band synchrony in the early-stage human somatosensory processing. (C) 2010 Elsevier Inc. All rights reserved..
41. てんかんのビデオ脳波モニタ.
42. Kei-ichiro Takase, Hiroshi Shigeto, Satoshi O. Suzuki, Hitoshi Kikuchi, Yasumasa Ohyagi, Jun-ichi Kira, Cortical kindling in a focal freeze lesion rat model, JOURNAL OF CLINICAL NEUROSCIENCE, 10.1016/j.jocn.2008.04.007, 16, 1, 94-98, 2009 Jan;16(1):94-8. Epub 2008 Nov 18.
, 2009.01, Focal cortical dysplasia (FCD) is of increasing interest as a cause of focal epilepsy. We aimed to determine whether the existence of FCD influences the epileptogenicity induced by electrical kindling stimulation of the cortices. We created an FCD rat model by focal contact of a frozen metal probe on the scalp immediately after birth. To produce afterdischarges (ADs), electrical stimulation was applied to the frontal cortices once daily for 20 consecutive days from postnatal day 38 (P38). Thresholds and durations of ADs were measured. Brains were exposed and examined histologically at P58. We observed mild FCD, which consisted of disorganized cortices with extra sulci: however, there was no statistical difference in the thresholds or durations of ADs between FCD rats and control animals. These results suggest that FCD might not influence vulnerability to epileptogenicity, at least in some patients with fluid FCD. (c) 2008 Elsevier Ltd. All rights reserved..
43. Kei-ichiro Takase, Hiroshi Shigeto, Satoshi O. Suzuki, Hitoshi Kikuchi, Yasumasa Ohyagi, Jun-ichi Kira, Prenatal freeze lesioning produces epileptogenic focal cortical dysplasia, EPILEPSIA, 10.1111/j.1528-1167.2008.01558.x, 49, 6, 997-1010, Epilepsia. 2008 Mar 4
, 2008.06, Purpose: Focal cortical dysplasia (FCD) is thought to be an important cause of intractable epilepsy. However, its epileptogenicity remains unclear. Therefore, we created a novel rat model by freeze lesioning during the late embryonic stage to verify whether FCD influences seizure activities.
Methods: At 18 days postconception, a frozen probe was placed on the left scalp of a Sprague-Dawley rat embryo through the uterus wall. For 40 consecutive days from postnatal day 38 (P38), electrical kindling stimulation was applied to the frontal lobes of male rat pups. Afterdischarges (ADs) were measured in both the cortex and hippocampus. Brain tissues were examined by immunohistochemistry.
Results: All brains from prenatally freeze-lesioned rats displayed severe disorganization of the cortical layers with randomly oriented dendrites/axons. In addition, heterotopic cortices were observed in 42.1% of cases. ADs in the cortex and hippocampus were significantly prolonged in freeze-lesioned rats compared with those in sham-operated and control rats. FCD rats also revealed early development of hippocampal kindling and spontaneous cortico-hippocampal spikes, even in the chronic EEG recordings. Immunoreactivities for N-methyl-D-aspartate receptor (NMDAR) subunit 2B and glutamate/aspartate transporter in the lesions were significantly enhanced compared with the nonlesioned side, even in the absence of electrical stimulation. After electrical stimulation, NMDAR1 and 2B were markedly upregulated not only in the FCD, but also in the hippocampus.
Conclusions: Prenatal freeze lesioning of the brain produces a severe neuronal migration disorder, closely mimicking human FCD. Our model suggests that FCD is associated with vulnerability to epilepsy, and may augment hippocampal epileptogenicity..
44. Christoph Kellinghaus, Gabriel Möddel, Hiroshi Shigeto, Zhong Ying, Berit Jacobsson, Jorge Gonzalez-Martinez, Candice Burrier, Damir Janigro, Imad M Najm, Dissociation between in vitro and in vivo epileptogenicity in a rat model of cortical dysplasia., Epileptic disorders : international epilepsy journal with videotape, 9, 1, 11-9, 9(1):11-9.
, 2007.03, OBJECTIVE: Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. METHODS: Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats. RESULTS: No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices. CONCLUSION: Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo..
45. H Shigeto, T Uehara, K Uchida, T Nomura, T Taniwaki, J Kira, Thalamic involvement of status epilepticus: diffusion-weighted image of MRI in two cases of status epilepticus, UNVEILING THE MYSTERY OF THE BRAIN: NEUROPHYSIOLOGICAL INVESTIGATION OF THE BRAIN FUNCTION, 10.1016/j.ics.2004.11.075, 1278, 193-196, 2005.11, Status epilepticus (SE) is prolonged and repetitive epileptic seizure. SE is associated with widespread neuronal necrosis in vulnerable regions of the brain. We obtained diffusion-weighted image of magnetic resonance imaging (DWI-MRI) from two cases with SE. Case I is a 55-year-old man who showed repetitive tonic seizures on his left side evolving to generalized tonic seizure. Seizure occurred every 20 min at maximum rate. Todd's palsy was seen on his left side. Electroencephalogram (EEG) showed repetitive high-amplitude sharp waves over the right front-central region, which continued 10 days with diminishing repetitive rate of sharp waves. DWI-MRI showed high signal intensity at the right frontal cortex and dorsomedial portion of the thalamus. Apparent diffusion coefficient (ADC) was low at the same area. Case 2 is a 37-year-old woman. She initially stopped speech evolving to generalized tonic seizure. The seizure disappeared 30 min later. Todd's palsy appeared on her right side. EEG showed repetitive spikes, polyspikes and slow waves with high amplitude over the left centro-parieto-tempolo-occipital region, which disappeared next day. DWI-MRI showed high signal intensity at the left parieto-tempolo-occipital lobes without the thalamic involvement. ADC was low at the same area. Thalamus was involved in case 1, but not in case 2. The fact may depend on the intensity of epileptic activity of neocortex. (c) 2004 Elsevier B.V. All rights reserved..
46. [Facioscapulohumeral muscular dystrophy with sinus dysfunction].
We report a 47-year-old man with facioscapulohumeral muscular dystrophy (FSHD) presenting with sinus dysfunction. He became unable to roll over and stand up at the age of 42, but he could still walk. Facial muscle involvement, scapular winging, asymmetrical involvement, funnel chest, and the absence of contractures were typical of FSHD. Electrocardiogram (ECG) and cardiac echogram showed the overload of both right atrium and ventricle. On Holter ECG, transient P wave inversion and P-P interval elongation (maximally 2.4 seconds) repeatedly appeared mainly during sleep. There was no bundle branch block, atrioventricular junctional rhythm, or increase of premature ventricular beats. Vital capacity was decreased (0.62 L, 16% of the predicted value). Arterial blood gas analysis showed hypercapnia and hypoxia which aggravated during sleep (PaCO2 87.3Torr, PaO2 41.5Torr). Sleep apnea was not observed. Intracardiac ECG was not performed and he died 2 weeks later. In FSHD, sinus node dysfunction may become distinct especially in the setting of respiratory failure..
47. Visual evoked cortical magnetic responses to checkerboard pattern reversal stimulation : a study on the neural generators of N75, P100 and N145.
48. Hiroshi Shigeto, Shozo Tobimatsu, Takato Morioka, Tomoya Yamamoto, Takuro Kobayashi, Motohiro Kato, Jerk-locked back averaging and dipole source localization of magnetoencephalographic transients in a patient with epilepsia partialis continua, Electroencephalography and Clinical Neurophysiology, 10.1016/S0013-4694(97)00040-0, 103, 4, 440-444, 1997.10, In order to localize the generator site of epilepfiform discharges, we applied the techniques of jerk-locked back averaging (JBA) of magnetoencephalographic (MEG) activities and dipole source localization in a patient with epilepsia partialis continua (EPC), who showed continuous, focal myoclonic jerks in the right arm. The myoclonic discharges in the right thenar muscle were used as a trigger pulse. JBA revealed consistent EEG and MEG transients that coincided consistently and constantly preceded the myoclonic jerks. The estimated dipoles of MEG were localized in a restricted area in the left precentral area, which closely correlated with the area of epileptic discharges recorded in electrocorticography. Therefore, JBA of MEG is considered to be a useful non-invasive method for localizing the epileptogenic area in EPC..
Presentations
1. Hiroshi Shigeto, How to choose AED in newly diagnosed epilepsy, 13th Asia Oceania Epilepsy Conference, 2021.06.
2. Mukaino T, Uehara T1, Yokoyama J, Okadome T, Sakata A, Arakawa T, Yokoyama S, Akamatsu 6, Shigeto H, Kira J-I, Time-dependent functional specialization of hippocampal subfields detected by MRI in patients with temporal lobe epilepsy, American Epilepsy Society Annual Meeting 2019, 2019.12.
3. Hideaki Tanaka, MD; Hiroshi Shigeto, MD, PhD; Shinji Ohara, MD, PhD; Toshio Matsushima, MD, PhD; Tooru Inoue, MD, PhD; Naoki Akamatsu, MD, PhD, Predictors of postsurgical seizure relapse and post-relapse after surgery of temporal lobe epilepsy in the era of new antiepileptic drugs, 33rd International Epilepsy Congress, 2019.06, [URL], Objective:
To assess prognostic factors predicting seizure recurrence after resective surgery for temporal lobe epilepsy patients who had chance to use new antiepileptic drugs (AEDs).

Methods:
We retrospectively investigated surgical outcomes in patients with neocortical or medial temporal lobe epilepsy who underwent temporal lobe resection between May 2014 and June 2017, and were observed for a minimum of one and half year after the surgery. To identify independent predictors for seizure relapse, we first used the univariate analysis (gender, seizure-onset age, using preoperative AEDs treatment, surgical side, pathology, etc.) to find significance differences and then used Cox’s proportional hazards analyses for multivariate analysis using results of univariate analyses.

Results:
A total of 41 consecutive patients were included in this study. Estimated epileptogenic zone in neocortex, existence of inter-ictal epileptiform discharges after operation, and duration of disease before surgery were significantly associated with seizure relapse, whereas preoperative treatment of new AEDs did not change the outcome: (1) Neocortical temporal lobe epilepsy compared to medial temporal lobe epilepsy (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.162-0.809; p=0.013), (2) Postoperative inter-ictal epileptiform discharges on EEG (HR 0.475, 95% CI 0.240-0.939, p=0.032), (3) Shorter duration of disease (HR 0.965, 95% CI 0.942-0.990, p=0.005).

Conclusions:
Our study disclosed that the patients with estimated epileptogenic zone in neocortex, postoperative inter-ictal epileptiform discharges, and shorter duration of disease before surgery are more likely to experience seizure recurrence postoperatively. Our results may be useful for selecting candidates for resective surgery in patients with temporal lobe epilepsy..
Membership in Academic Society
  • Japan Biomagnetism and Bioelectromagnetics Society
  • Integrated sleep medicine society Japan
  • Japanese Society of Cognitive Neuroscience
  • Japanese society of sleep research
Educational
Educational Activities
In the undergraduate teaching curriculum, lectures and practical training on neurophysiology, respiratory physiology, cardiovascular physiology, epilepsy, involuntary movement and sleep disorders are given. For the postgraduate education, we provide guidance on research based on neurophysiology and molecular biology.
Social
Professional and Outreach Activities
Chief of the committee regarding regional and international relationship .