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Article ; Online: O

Anan, Mitsuhiro / Del Maestro, Rolando Fausto / Hata, Nobuhiro / Fujiki, Minoru

Neuropathology : official journal of the Japanese Society of Neuropathology

2023 Volume 44, Issue 1, Page(s) 41–46

Abstract: Glioblastoma (GBM) remains a treatment-resistant malignant brain tumor in large part because of its genetic heterogeneity and epigenetic plasticity. In this study, we investigated the epigenetic heterogeneity of GBM by evaluating the methylation status ... ...

Abstract	Glioblastoma (GBM) remains a treatment-resistant malignant brain tumor in large part because of its genetic heterogeneity and epigenetic plasticity. In this study, we investigated the epigenetic heterogeneity of GBM by evaluating the methylation status of the O
MeSH term(s)	Humans ; Glioblastoma/genetics ; Glioblastoma/pathology ; Methyltransferases/genetics ; HeLa Cells ; DNA Methylation ; DNA Modification Methylases/genetics ; Brain Neoplasms/genetics ; Clone Cells/pathology ; RNA, Messenger ; DNA Repair Enzymes/genetics
Chemical Substances	Methyltransferases (EC 2.1.1.-) ; DNA Modification Methylases (EC 2.1.1.-) ; RNA, Messenger ; DNA Repair Enzymes (EC 6.5.1.-)
Language	English
Publishing date	2023-06-29
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12931
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Article: Monophasic-quadri-burst stimulation robustly activates bilateral swallowing motor cortices.

Fujiki, Minoru / Hata, Nobuhiro / Anan, Mitsuhiro / Matsushita, Wataru / Kawasaki, Yukari / Fudaba, Hirotaka

Frontiers in neuroscience

2023 Volume 17, Page(s) 1163779

Abstract: A stable, reliable, non-invasive, quantitative assessment of swallowing function remains to be established. Transcranial magnetic stimulation (TMS) is commonly used to aid in the diagnosis of dysphagia. Most diagnostic applications involve single-pulse ... ...

Abstract	A stable, reliable, non-invasive, quantitative assessment of swallowing function remains to be established. Transcranial magnetic stimulation (TMS) is commonly used to aid in the diagnosis of dysphagia. Most diagnostic applications involve single-pulse TMS and motor evoked potential (MEP) recordings, the use of which is not clinically suitable in patients with severe dysphagia given the large variability in MEPs measured from the muscles involved in swallowing. Previously, we developed a TMS device that can deliver quadripulse theta-burst stimulation in 16 monophasic magnetic pulses through a single coil, enabling the measurement of MEPs related to hand function. We applied a system for MEP conditioning that relies on a 5 ms interval-monophasic quadripulse magnetic stimulation (QPS5) paradigm to produce 5 ms interval-four sets of four burst trains; quadri-burst stimulation (QBS5), which is expected to induce long-term potentiation (LTP) in the stroke patient motor cortex. Our analysis indicated that QBS5 conditioned left motor cortex induced robust facilitation in the bilateral mylohyoid MEPs. Swallowing dysfunction scores after intracerebral hemorrhage were significantly correlated with QBS5 conditioned-MEP parameters, including resting motor threshold and amplitude. The degree of bilateral mylohyoid MEP facilitation after left side motor cortical QBS5 conditioning and the grade of severity of swallowing dysfunction exhibited a significant linear correlation (
Language	English
Publishing date	2023-05-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1163779
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Article: Quantitative GABA magnetic resonance spectroscopy as a measure of motor learning function in the motor cortex after subarachnoid hemorrhage.

Sugita, Kenji / Anan, Mitsuhiro / Matsuta, Hiroyuki / Shimomura, Tsuyoshi / Fudaba, Hirotaka / Hata, Nobuhiro / Fujiki, Minoru

Frontiers in neurology

2023 Volume 14, Page(s) 1173285

Abstract: The neural mechanisms underlying gross and fine motor dysfunction after subarachnoid hemorrhage (SAH) remain unknown. The γ-aminobutyric acid (GABA) deficit hypothesis proposes that reduced neuronal GABA concentrations and the subsequent lack of GABA- ... ...

Abstract	The neural mechanisms underlying gross and fine motor dysfunction after subarachnoid hemorrhage (SAH) remain unknown. The γ-aminobutyric acid (GABA) deficit hypothesis proposes that reduced neuronal GABA concentrations and the subsequent lack of GABA-mediated inhibition cause motor impairment after SAH. This study aimed to explore the correlation between GABA levels and a behavioral measure of motor performance in patients with SAH. Motor cortical GABA levels were assessed in 40 patients with SAH and 10 age-matched healthy controls using proton magnetic resonance spectroscopy. The GABA and N-acetylasparate (NAA) ratio was measured in the normal gray matter within the primary motor cortex. The relationship between GABA concentration and hand-motor performance was also evaluated. Results showed significantly lower GABA levels in patients with SAH's left motor cortex than in controls (GABA/NAA ratio: 0.282 ± 0.085 vs. 0.341 ± 0.031, respectively;
Language	English
Publishing date	2023-10-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1173285
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Article: Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid.

Otsuji, Ryosuke / Fujioka, Yutaka / Hata, Nobuhiro / Kuga, Daisuke / Hatae, Ryusuke / Sangatsuda, Yuhei / Nakamizo, Akira / Mizoguchi, Masahiro / Yoshimoto, Koji

Cancers

2024 Volume 16, Issue 5

Abstract: Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally ... ...

Abstract	Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood-brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.
Language	English
Publishing date	2024-02-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16051009
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Article ; Online: Characteristics of deceased subjects transported to a postmortem imaging center due to unusual death related to epilepsy.

Ito, Yoshiki / Hata, Nobuhiro / Maesawa, Satoshi / Tanei, Takafumi / Ishizaki, Tomotaka / Mutoh, Manabu / Hashida, Miki / Kobayashi, Yutaka / Saito, Ryuta

Epilepsia open

2024 Volume 9, Issue 2, Page(s) 592–601

Abstract: Objective: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also ... ...

Abstract	Objective: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). Methods: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. Results: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. Significance: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. Plain language summary: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.
MeSH term(s)	Humans ; Drowning ; Postmortem Imaging ; Troponin T/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/diagnosis ; Autopsy ; Cerebrovascular Disorders
Chemical Substances	Troponin T
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ISSN	2470-9239
ISSN (online)	2470-9239
DOI	10.1002/epi4.12891
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Article ; Online: Nivolumab therapy for a pediatric-onset primary intracranial melanoma.

Oba, Utako / Koga, Yuhki / Hata, Nobuhiro / Oda, Yoshinao / Ohga, Shouichi

Pediatrics international : official journal of the Japan Pediatric Society

2022 Volume 64, Issue 1, Page(s) e14956

MeSH term(s)	Brain Neoplasms/drug therapy ; Child ; Humans ; Melanoma/drug therapy ; Nivolumab/therapeutic use
Chemical Substances	Nivolumab (31YO63LBSN)
Language	English
Publishing date	2022-04-28
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1470376-2
ISSN	1442-200X ; 1328-8067
ISSN (online)	1442-200X
ISSN	1328-8067
DOI	10.1111/ped.14956
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Article ; Online: Predicting TERT promoter mutation status using

Yamashita, Koji / Hatae, Ryusuke / Kikuchi, Kazufumi / Kuga, Daisuke / Hata, Nobuhiro / Yamamoto, Hidetaka / Obara, Makoto / Yoshimoto, Koji / Ishigami, Kousei / Togao, Osamu

Neuroradiology

2023 Volume 65, Issue 8, Page(s) 1205–1213

Abstract: Purpose: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated ... ...

Abstract	Purpose: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated with tumor aggressiveness. The aim of this study was to identify features from MR spectroscopy (MRS) and multi-exponential models of DWI distinguishing wild-type TERT (TERTw) from TERT promoter mutation (TERTm) in IDH-wildtype diffuse astrocytic glioma. Methods: Participants comprised 25 adult patients with IDH-wildtype diffuse astrocytic glioma. Participants were classified into TERTw and TERTm groups. Point-resolved spectroscopy sequences were used for MRS data acquisition. DWI was performed with 13 different b-factors. Peak height ratios of NAA/Cr and Cho/Cr were calculated from MRS data. Mean apparent diffusion coefficient (ADC), perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D), distributed diffusion coefficient (DDC), and heterogeneity index (α) were obtained using multi-exponential models from DWI data. Each parameter was compared between TERTw and TERTm using the Mann-Whitney U test. Correlations between parameters derived from MRS and DWI were also evaluated. Results:* NAA/Cr and Cho/Cr were both higher for TERTw than for TERTm. The α of TERTw was smaller than that of TERTm, while the f of TERTw was higher than that of TERTm. NAA/Cr correlated negatively with α, but not with other DWI parameters. Cho/Cr did not show significant correlations with any DWI parameters. Conclusion: The combination of NAA/Cr and α may have merit in clinical situation to predict the TERT mutation status of IDH-wildtype diffuse astrocytic glioma without intense enhancement.
MeSH term(s)	Adult ; Humans ; Isocitrate Dehydrogenase/genetics ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Diffusion Magnetic Resonance Imaging/methods ; Astrocytoma/diagnostic imaging ; Astrocytoma/genetics ; Astrocytoma/pathology ; Magnetic Resonance Spectroscopy/methods ; Mutation ; Telomerase/genetics
Chemical Substances	Isocitrate Dehydrogenase (EC 1.1.1.41) ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2023-06-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	123305-1
ISSN	1432-1920 ; 0028-3940
ISSN (online)	1432-1920
ISSN	0028-3940
DOI	10.1007/s00234-023-03177-y
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Article ; Online: Lateral Lumbar Interbody Fusion within Three-level for Patients with Neurological Symptoms due to Vertebral Fragility Fractures in the Lumbar Spine.

Nagashima, Yoshitaka / Nishimura, Yusuke / Kanemura, Tokumi / Hata, Nobuhiro / Satake, Kotaro / Akahori, Sho / Ishii, Motonori / Tanei, Takafumi / Takayasu, Masakazu / Saito, Ryuta

Neurologia medico-chirurgica

2023 Volume 63, Issue 12, Page(s) 548–554

Abstract: There is a lack of agreement on whether minimally invasive lateral lumbar intervertebral fusion (LLIF) is a suitable treatment option for vertebral fragility fractures (VFFs). Hence, we sought to evaluate the efficacy and safety of LLIF in the management ...

Abstract	There is a lack of agreement on whether minimally invasive lateral lumbar intervertebral fusion (LLIF) is a suitable treatment option for vertebral fragility fractures (VFFs). Hence, we sought to evaluate the efficacy and safety of LLIF in the management of VFF with neurological deficits in the lumbar spine. Between April 2015 and March 2020, we conducted a retrospective observational study of patients with VFF treated with three-level or less LLIF. The participants had previously received conservative treatment but had not been able to control their neurological symptoms. To assess the outcomes of the LLIF procedures, the patients were followed up for a minimum of 1 year. Clinical and radiological results, which include the timing and location of the bony fusion, were analyzed. The study involved 19 patients with 23 vertebral fracture levels. The residual height of the fractured vertebra was found to be 57.0 ± 12.3% of the height of the adjacent level. The mean Japanese Orthopedic Association score significantly improved postoperatively. Postoperative radiological parameters were significantly maintained at 1 year, and lumbar lordosis was maintained at the last follow-up (45.0 ± 26.7). In total 31 LLIF levels, bone fusion was observed in four levels at 6 months postoperatively, in 16 levels at 1 year, and in 23 levels at the last follow-up. The facet joint had the highest bony fusion location. LLIF within three levels can be safely performed in certain VFF cases with sufficient residual vertebral height.
MeSH term(s)	Humans ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/surgery ; Lumbosacral Region ; Plastic Surgery Procedures ; Retrospective Studies ; Spinal Fractures/diagnostic imaging ; Spinal Fractures/surgery ; Spinal Fractures/etiology ; Spinal Fusion/methods ; Treatment Outcome
Language	English
Publishing date	2023-10-18
Publishing country	Japan
Document type	Observational Study ; Journal Article
ZDB-ID	604061-5
ISSN	1349-8029 ; 0470-8105
ISSN (online)	1349-8029
ISSN	0470-8105
DOI	10.2176/jns-nmc.2023-0064
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Article ; Online: In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo.

Hata, Nobuhiro / Fujioka, Yutaka / Otsuji, Ryosuke / Kuga, Daisuke / Hatae, Ryusuke / Sangatsuda, Yuhei / Amemiya, Takeo / Noguchi, Naoki / Sako, Aki / Fujiki, Minoru / Mizoguchi, Masahiro / Yoshimoto, Koji

Neuropathology : official journal of the Japanese Society of Neuropathology

2024

Abstract: Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, ...

Abstract	Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as "Drug resistance gene testing for anticancer chemotherapy" and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.
Language	English
Publishing date	2024-03-13
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12970
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Article: Spinal Cord Stimulation for Neuropathic Pain following a Spinal Cord Lesion with Past Spinal Surgical Histories Using a Paddle Lead Placed on the Rostral Side of the Lesion: Report of Three Cases.

Fukaya, Nobuhisa / Tanei, Takafumi / Nishimura, Yusuke / Hara, Masahito / Hata, Nobuhiro / Nagashima, Yoshitaka / Maesawa, Satoshi / Araki, Yoshio / Saito, Ryuta

NMC case report journal

2022 Volume 9, Page(s) 349–355

Abstract: Spinal cord parenchymal lesions may induce intractable neuropathic pain. However, the efficacy of conventional spinal cord stimulation for the neuropathic pain following spinal cord lesions remains to be controversial. In this study, we present three ... ...

Abstract	Spinal cord parenchymal lesions may induce intractable neuropathic pain. However, the efficacy of conventional spinal cord stimulation for the neuropathic pain following spinal cord lesions remains to be controversial. In this study, we present three cases of spinal cord stimulation using a paddle lead at the rostral side of the spinal lesion causing pain symptoms. Good pain reductions were achieved using conventional stimulation in one case and using differential target multiplexed stimulation in two cases. Case 1: A 55-year-old man presented with neuropathic pain affecting his bilateral upper extremities due to a traumatic cervical spinal cord injury. Conventional stimulation via a paddle-type electrode was able to reduce the pain from 8 to 4 via a visual analog scale. Case 2: A 67-year-old man had undergone three spinal surgeries. He presented with pain and numbness of bilateral lower extremities due to a spinal cord lesion by thoracic disc herniation. Differential target multiplexed stimulation via a paddle-type electrode achieved excellent pain reduction, that is, from 9 to 2 on the visual analog scale. Case 3: An 80-year-old man presented with pain in his bilateral upper extremities due to a cervical spinal cord lesion caused by compression and spinal canal stenosis. Posterior cervical decompression and paddle-type electrode placement were performed simultaneously. Differential target multiplexed stimulation was able to achieve excellent pain reduction, from 7 to 2 on the visual analog scale. Spinal cord stimulation using a paddle lead at the rostral side of the spinal lesion and differential target multiplexed stimulation may provide significant opportunities for patients with intractable neuropathic pain following spinal cord lesions.
Language	English
Publishing date	2022-10-13
Publishing country	Japan
Document type	Case Reports
ISSN	2188-4226
ISSN	2188-4226
DOI	10.2176/jns-nmc.2022-0218
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