in non-CJD patients registered in our CJD surveillance included status epilepticus, diffuse Lewy disease, Hashimoto encephalopathy, Wernicke encephalopathy ...
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Abstracts / Journal of the Neurological Sciences 381 (2017) 54–180
Medicine, Radiology, Tokushima, Japan; hTohoku University Graduate School of Medicine, Pathology, Sendai, Japan; iNational Center for Neurology and Psychiatry, Neurology, Tokyo, Japan; jKanazawa University Graduate School of Medicine, Neurology, Kanazawa, Japan
394 WCN17-1456 FREE PAPERS: STEM CELLS AND GENE THERAPY The exon 45 skipping therapy of induced pluripotent stem cells derived cardiomyocyte from the DMD patient with exon 46-55 deletion a
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M. Sato , D. Miyazaki , Y. Shiba , Y. Echigoya , T. Yokota , Y. Aoki , S. Takedae, A. Nakamuraa. aShinshu University, Department of Medicine Neurology and Rheumatology, Matsumoto, Japan; bShinshu University, Intractable Disease Care Center, Matsumoto, Japan; cShinshu University, Institute for Biomedical Sciences, Matsumoto, Japan; dUniversity of Alberta, Department of Medical Genetics- School of Human Development- Faculty of Medicine and Dentistry, Edmonton- Alberta, Canada; eNational Institute of Neuroscience- National Center of Neurology and Psychiatry NCNP, Department of Molecular Therapy, Kodaira- Tokyo, Japan Background: Duchenne muscular dystrophy (DMD) is an X-linked lethal muscular disorder and is caused by a mutation in the DMD gene encoding dystrophin. It has been reported that a deletion of exon 45–55 covering a whole hot-spot mutational region of the DMD gene causes a very mild Becker muscular dystrophy or asymptomatic dystrophinopathy. In dystrophinopathy, cardiomyopathy sometimes is a critical issue; therefore, the DMD specific induced pluripotent stem cells(iPSC)-derived cardiomyocytes might be a useful for elucidation of the pathomechanism and evaluation of the therapeutic efficacy. Objective: The aim of this study is 1) to establish differentiated cardiomyocytes derived from iPSC of a DMD patient having a deletion of exon 46–55, and 2) to perform the exon 45 skipping therapy with phosphorodiamidate morpholino oligomers (PMO) as AOs to the differentiated cardiomyocytes and 3) to evaluate the skipping efficiency and restoration of dystrophin expression. Patients and Methods/Material and Methods: First, we established iPSC lines from T-lymphocytes donated from DMD patients having a deletion of exons 46–55, and differentiated the iPSC to cardiomyocytes. Next, we performed exon 45 skipping therapy to the cardiomyocytes using exon 45 specific PMO and examined skipping efficiency by RT-PCR and dystrophin expression by western blotting. Results: RT-PCR analysis showed that the skipping efficiency of exon 45 which achieved by 5μM and 10μM PMO was dose-depended manner. Western blotting revealed that the truncated dystrophin with a deletion of exon 45–55 was restored. Conclusion: We demonstrated that the exon skipping efficiency was depend on the PMO dosage, and successfully detected the restored dystrophin expression in DMD-iPSC-derived cardiomyocytes.
Background: Generalized periodic EEG patterns consist of 4 subtypes; periodic suppression bursts seen in cerebral anoxia and general anesthesia, periodic slow wave complexes seen in SSPE, repetitive sharp transients seen in CJD, and periodic tri-phasic waves seen in metabolic encephalopathy. The periodic synchronous discharges, PSDs in CJD correspond to the repetitive sharp transients. Objective: The aim of our study is to evaluate how useful PSDs as a basic clue for diagnosing CJD, along with diffusion-weighted MRI, and biochemical markers of 14-3-3 and tau proteins. Patients and Methods/Material and Methods: We investigated the occurrence rate of PSDs in 610 sporadic, 171 genetic, and 13 dura CJD patients. Results: The occurrence rate of PSDs in Japanese CJD surveillance was, 72% in sporadic, 24% in genetic, and 62% in dura CJD patients. Among 171 genetic CJD patients, the occurrence rate of PSDs was 3% in V180I mutation CJD (0/53), 14% in P102L mutation CJD (2/22)、70% in E200K mutation CJD (5/8), and 71% in M232R mutation CJD patients. Conclusion: We proposed grading of PSDs in CJD, Grade A~ Grade E. Grade A was defined as typical PSDs. Grade B was defined as PSDs of a relatively longer periodic interval. Grade C was defined as PSDs of a relatively rare appearance. Grade D was defined as PSDs of a rudimentary appearance. Grade E was defined as absent PSDs. Diagnosis in non-CJD patients registered in our CJD surveillance included status epilepticus, diffuse Lewy disease, Hashimoto encephalopathy, Wernicke encephalopathy, uremic encephalopathy, and lateral sinus thrombosis. doi:10.1016/j.jns.2017.08.421
396 WCN17-2648 FREE PAPERS: NEUROPHYSIOLOGY 2 Higher-order motor cortices actively engage in motor inhibition: Cortical stimulation and event-related potentials as an evidence from subdural grid electrodes H. Takeyamaa, R. Matsumotoa, K. Usamia, A. Shimotakeb, T. Kuniedac, S. Miyamotoc, R. Takahashia, A. Ikedab. aKyoto University Graduate School of Medicine, Neurology, Kyoto, Japan; bKyoto University Graduate School of Medicine, Epilepsy- Movement disorders and Physiology, Kyoto, Japan; c Kyoto University Graduate School of Medicine, Neurosurgery, Kyoto, Japan
doi:10.1016/j.jns.2017.08.420
395 WCN17-2589 FREE PAPERS: NEUROPHYSIOLOGY 2 Periodic encephalographic study in nation-wide Creutzfeldt Jakob disease surveillance in Japan Y. Kuroiwaa, I. Takumib, H. Muraic, K. Kasugad, Y. Nakamurae, K. Fujinoa, T. Hiraia, Y. Kawabataa, Y. Babaa, K. Satof, M. Haradag, T. Kitamotoh, T. Tsukamotoi, M. Yamadaj, H. Mizusawai. aTeikyo University School of Medicine- Mizonokuchi Hospital, Neurology, Kawasaki, Japan; bNihon Medical University, Neurosurgery, Kawasaki, Japan; cKyushu University Graduate School of Medicine, Neurology, Fukuoka, Japan; dNiigata University Graduate School of Medicine, Neurology, Niigata, Japan; eJichi Medical University, Epidemiology, Shimono, Japan; fNagasaki University Graduate School of Medicine, Neurology, Nagasaki, Japan; gTokushima University Graduate School of
Background: Motor inhibition is the important brain function in the frontal lobe and impaired in neurological diseases such as Parkinson’s disease. Previous neuroimaging studies implicated its processing in the pre-supplementary motor area (Pre-SMA), dorsal premotor area (PMd), and ventral premotor area (PMv). Objective: The objective of the current study is to clarify and clinically map the key areas in the frontal lobe for motor inhibition. Patients and Methods/Material and Methods: The subjects were 8 epilepsy patients (4 male) with chronic subdural electrode implantation for presurgical evaluation covering the frontal lobe (4 right, 4 left hemisphere) (IRB C533). Event-related potentials (ERPs) were recorded during a Go/No-Go paradigm. 50 Hz electrical stimulation (4-8 mA, 500 ms) was applied to the cortical areas with ERPs specific to No-Go trials (No-Go ERPs). Stimulation was applied in both Go and No-Go trials, and the reaction time and error rate were analyzed. Results: No-Go ERPs were recorded in Pre-SMA (4/4 patients), PMd (4/4), and PMv (5/5). 50 Hz electrical stimulation was applied to
