Kyushu University [Hiroshi Shigeto (Professor) Faculty of Medical Sciences, Department of Health Sciences]

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Hiroshi Shigeto
Professor
Medical technology
Department of Health Sciences
Faculty of Medical Sciences
Last modified date：2023.06.28

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Department of Health Sciences
Graduate School of Medical Sciences

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Biological Sciences and Technology
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Neurology

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1.	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。.
2.	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..
3.	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.
4.	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..
5.	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. .
6.	てんかんのビデオ脳波モニタ.

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..