Hiroshi Ohmae, Taku Matsuda, Maki Fujimoto, Yuka Nakanowatari, Megumi Yamada, Nori Sato, Kimiko Umemura, Ryoma Morigaki, Tetsuya Matsuura and Yasushi Takagi : Safety and Selection Criteria of Single-joint Hybrid Assistive Limb for Upper Limb Paralysis After Stroke: A Phase I Trial., Neurologia Medico-Chirurgica, 65, 1, 15-21, 2024.
(要約)
Robotic rehabilitation is a high-intensity intervention for upper limb paralysis after a stroke. This study explored the safety and feasibility of using a single-joint hybrid assistive limb (HAL-SJ) exoskeletal device for upper limb paralysis in patients with acute stroke. In total, 11 patients with stroke (6 with moderate paralysis and 5 with severe paralysis) were enrolled between October 2021 and October 2023 in a stroke care unit. The patients underwent HAL training 3 times a week for 6 sessions. No serious adverse events related to HAL-SJ occurred, and participants demonstrated significant improvements in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) (pre- vs. post-intervention; p < 0.05). The minimal clinically important difference (MCID) for FMA-UE was surpassed in 5 patients (83.3%) with moderate paralysis and 2 (40.0%) with severe paralysis. Regarding ARAT, 4 patients (66.7%) with moderate paralysis exceeded the MCID, whereas none (0.0%) with severe paralysis did. These findings suggest that HAL-SJ is both safe and feasible, particularly for individuals with moderate paralysis.
Hiroshi Nakanishi, Ryoma Morigaki, Joji Fujikawa, Hiroshi Ohmae, Keisuke Shinohara, Nobuaki Yamamoto, Yuishin Izumi and Yasushi Takagi : Online training program maintains motor functions and quality of life in patients with Parkinson's disease., Frontiers in Digital Health, 6, 1486662, 2024.
(要約)
= 0.341) in the TUG test showed significant differences before and after the intervention.
Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto and Yasushi Takagi : Cranial geometry in patients with dystonia and Parkinson's disease., Scientific Reports, 13, 1, 2023.
(要約)
Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.
Nobuaki Yamamoto, Kazutaka Kuroda, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Kenji Shimada, Ryoma Morigaki, Yasuhisa Kanematsu, Yuishin Izumi and Yasushi Takagi : Long-sheath Introducer-assisted Revascularization (L-SHARE) Technique for Treating Large-vessel Occlusion by a Giant Clot, Internal Medicine, 62, 6, 909-913, 2023.
(要約)
Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.
Taku Matsuda, Ryoma Morigaki, Yuki Matsumoto, Hideo Mure, Kazuhisa Miyake, Masahito Nakataki, Masafumi Harada and Yasushi Takagi : Obsessivecompulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia, Scientific Reports, 12, 1, 20350, 2022.
(要約)
We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ϱ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ϱ = 0.72, p = 0.023; left: ϱ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.
J Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, H Nakanishi, T Oda, Yuishin Izumi and Yasushi Takagi : Diagnosis and Treatment of Tremor in Parkinson's Disease Using Mechanical Devices, Life, 13, 1, 78, 2022.
(要約)
Parkinsonian tremors are sometimes confused with essential tremors or other conditions. Recently, researchers conducted several studies on tremor evaluation using wearable sensors and devices, which may support accurate diagnosis. Mechanical devices are also commonly used to treat tremors and have been actively researched and developed. Here, we aimed to review recent progress and the efficacy of the devices related to Parkinsonian tremors. The PubMed and Scopus databases were searched for articles. We searched for "Parkinson disease" and "tremor" and "device". Eighty-six articles were selected by our systematic approach. Many studies demonstrated that the diagnosis and evaluation of tremors in patients with PD can be done accurately by machine learning algorithms. Mechanical devices for tremor suppression include deep brain stimulation (DBS), electrical muscle stimulation, and orthosis. In recent years, adaptive DBS and optimization of stimulation parameters have been studied to further improve treatment efficacy. Due to developments using state-of-the-art techniques, effectiveness in diagnosing and evaluating tremor and suppressing it using these devices is satisfactorily high in many studies. However, other than DBS, no devices are in practical use. To acquire high-level evidence, large-scale studies and randomized controlled trials are needed for these devices.
Joji Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, Teruo Oda, Hiroshi Nakanishi, Yuishin Izumi and Yasushi Takagi : Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials., Frontiers in Aging Neuroscience, 14, 2022.
(要約)
Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yuishin Izumi and Yasushi Takagi : Percutaneous Transluminal Angioplasty and Stenting Using an Aspiration Catheter, Journal of Neuroendovascular Therapy, 16, 5, 277-282, 2021.
(要約)
<p><b>Objective</b>: During percutaneous transluminal angioplasty (PTA) for the vertebral artery, occlusion of the subclavian artery using a balloon guiding catheter may be useful to prevent embolism of clots and/or debris distal to an atherosclerotic lesion. However, when placing a balloon guiding catheter at the intended vessels is difficult, it may be useful to use an aspiration catheter (AC) for mechanical thrombectomy as an intermediate catheter to suction way clots and/or debris. We report two cases in which PTA was performed for an atherosclerotic lesion at the intracranial vertebral artery using an AC, which ended without complications.</p><p><b>Case Presentations</b>: Case 1: A 74-year-old man presented with dysarthria and was admitted to our hospital. MRI revealed severe left vertebral artery stenosis and diffuse cerebral infarct areas at the territory of the posterior circulation. The patient had an abdominal aortic aneurysm and abnormally shaped left tortuous subclavian artery. Therefore, we performed PTA and stenting via the left brachial artery. We guided a 6-Fr long sheath to the left subclavian artery, and a 6-Fr AC for thrombectomy was guided through the long sheath to the V4 portion of the left vertebral artery. Thereafter, PTA was carried out under manual aspiration from the AC. As restenosis at the atherosclerotic lesion occurred after PTA, we performed stenting using a coronary stent system for this lesion under manual aspiration from the AC. No new infarct areas were observed on post-procedural MRI. Case 2: A 74-year-old woman presented with dysarthria and was admitted to our hospital. MRI demonstrated basilar artery occlusion and diffuse cerebral infarct areas at the territory of the posterior circulation. As her symptom worsened after admission, we performed urgent mechanical thrombectomy. We first performed thrombectomy using a stent retriever and then performed PTA and stenting (PTAS) for residual basilar artery stenosis via the AC under manual aspiration.</p><p><b>Conclusion</b>: When it is difficult to place a guiding catheter at the intended vessels during PTA, an AC may be useful to prevent distal embolization.</p>
Hiroshi Koyama, Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Taku Matsuda, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Satoshi Goto and Yasushi Takagi : Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia, Life, 11, 6, 477, 2021.
(要約)
Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.
Daisy Ma Tabuena, Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Nobuaki Yamamoto, Kazuhisa Miyake, Taku Matsuda, Yuishin Izumi, Yasushi Takagi, P Rollin Tabuena and Toshitaka Kawarai : Ataxia with vitamin E deficiency in the Philippines: A case report of two siblings., The Journal of Medical Investigation : JMI, 68, 3.4, 400-403, 2021.
(要約)
Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.
Nobuaki Yamamoto, Yuishin Izumi, Yuki Yamamoto, K Kuroda, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki and Yasushi Takagi : Factors associated with DWI-ASPECTS score in patients with acute ischemic stroke due to cerebral large vessel occlusion, Clinical Neurology and Neurosurgery, 199, 106316, 2020.
(要約)
The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission. We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings. This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p < 0.001, odds ratio 0.31, p = 0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission.
(キーワード)
Aged / Aged, 80 and over / Brain Ischemia / Cerebrovascular Disorders / Diffusion Magnetic Resonance Imaging / Female / Humans / Ischemic Stroke / Male / Middle Aged / Patient Admission / Prospective Studies / Retrospective Studies / Severity of Illness Index
Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Koji Fujita, Taku Matsuda, Yoko Yamamoto, Masahito Nakataki, Tetsuya Okahisa, Yuki Matsumoto, Kazuhisa Miyake, Nobuaki Yamamoto, Ryuji Kaji, Yasushi Takagi and Satoshi Goto : Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components., Brain Sciences, 10, 9, 636, 2020.
(要約)
The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.
Hideo Mure, Naoto Toyoda, Ryoma Morigaki, Koji Fujita and Yasushi Takagi : Clinical Outcome and Intraoperative Neurophysiology of the Lance-Adams Syndrome Treated with Bilateral Deep Brain Stimulation of the Globus Pallidus Internus: A Case Report and Review of the Literature., Stereotactic and Functional Neurosurgery, 98, 6, 399-403, 2020.
(要約)
Our results show that impairment in the basal ganglion circuitry might be involved in the pathogenesis of myoclonus in patients with LAS.
Makoto Kinoshita, Masahito Nakataki, Ryoma Morigaki, Satsuki Sumitani, Satoshi Goto, Ryuji Kaji and Tetsuro Ohmori : Turning on the Left Side Electrode Changed Depressive State to Manic State in a Parkinson's Disease Patient Who Received Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report., Clinical Psychopharmacology and Neuroscience, 16, 4, 494-496, 2018.
(要約)
No previous reports have described a case in which deep brain stimulation elicited an acute mood swing from a depressive to manic state simply by switching one side of the bilateral deep brain stimulation electrode on and off. The patient was a 68-year-old woman with a 10-year history of Parkinson's disease. She underwent bilateral subthalamic deep brain stimulation surgery. After undergoing surgery, the patient exhibited hyperthymia. She was scheduled for admission. On the first day of admission, it was clear that resting tremors in the right limbs had relapsed and her hyperthymia had reverted to depression. It was discovered that the left-side electrode of the deep brain stimulation device was found to be accidentally turned off. As soon as the electrode was turned on, motor impairment improved and her mood switched from depression to mania. The authors speculate that the lateral balance of stimulation plays an important role in mood regulation. The current report provides an intriguing insight into possible mechanisms of mood swing in mood disorders.
Toshitaka Kawarai, Ryosuke Miyamoto, Eiji Nakagawa, Reiko Koichihara, Takashi Sakamoto, Hideo Mure, Ryoma Morigaki, Hidetaka Koizumi, Ryosuke Oki, Celeste Montecchiani, Carlo Caltagirone, Antonio Orlacchio, Ayako Hattori, Hideaki Mashimo, Yuishin Izumi, Takahiro Mezaki, Satoko Kumada, Makoto Taniguchi, Fusako Yokochi, Shinji Saitoh, Satoshi Goto and Ryuji Kaji : Phenotype variability and allelic heterogeneity in KMT2B-Associated disease., Parkinsonism & Related Disorders, 2018.
(要約)
We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.
Toshitaka Kawarai, Ryoma Morigaki, Ryuji Kaji and Satoshi Goto : Clinicopathological Phenotype and Genetics of X-Linked Dystonia-Parkinsonism (XDP; DYT3; Lubag)., Brain Sciences, 7, 7, 72, 2017.
(要約)
X-linked dystonia-parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or "Lubag" disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in the later years of life. Among the primary monogenic dystonias, XDP has been identified as a transcriptional dysregulation syndrome with impaired expression of the TAF1 (TATA box-binding protein associated factor 1) gene, which is a critical component of the cellular transcription machinery. The major neuropathology of XDP is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen). XDP may be used as a human disease model to elucidate the pathomechanisms by which striatal neurodegeneration leads to dystonia symptoms. In this article, we introduce recent advances in the understanding of the interplay between pathophysiology and genetics in XDP.
Ryoma Morigaki and Satoshi Goto : Striatal Vulnerability in Huntington's Disease: Neuroprotection Versus Neurotoxicity., Brain Sciences, 7, 6, 2017.
(要約)
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.
Ryoma Morigaki, Hideo Mure, Ryuji Kaji, Shinji Nagahiro and Satoshi Goto : Therapeutic Perspective on Tardive Syndrome with Special Reference to Deep Brain Stimulation, Frontiers in Psychiatry, 7, 207, 2016.
(要約)
Tardive syndrome (TDS) is a potentially permanent and irreversible hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Guidelines published by the American Academy of Neurology recommend pharmacological first-line treatment for TDS with clonazepam (level B), ginkgo biloba (level B), amantadine (level C), and tetrabenazine (level C). Recently, a class II study provided level C evidence for use of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with TDS. Although the precise pathogenesis of TDS remains to be elucidated, the beneficial effects of GPi-DBS in patients with TDS suggest that the disease may be a basal ganglia disorder. In addition to recent advances in understanding the pathophysiology of TDS, this article introduces the current use of DBS in the treatment of medically intractable TDS.
Ryoma Morigaki and Satoshi Goto : Putaminal Mosaic Visualized by Tyrosine Hydroxylase Immunohistochemistry in the Human Neostriatum., Frontiers in Neuroanatomy, 10, 2016.
(要約)
Among the basal ganglia-thalamocortical circuits, the putamen plays a critical role in the "motor" circuits that control voluntary movements and motor learning. The human neostriatum comprises two functional subdivisions known as the striosome (patch) and matrix compartments. Accumulating evidence suggests that compartment-specific dysregulations of dopamine activity might be involved in the disease-specific pathology and symptoms of human striatal diseases including movement disorders. This study was undertaken to examine whether or how striatal dopaminergic innervations are organized into the compartmentalized architecture found in the putamen of adult human brains. For this purpose, we used a highly sensitive immunohistochemistry (IHC) technique to identify tyrosine hydroxylase (TH; EC 1.14.16.2), a marker for striatal dopaminergic axons and terminals, in formalin-fixed paraffin-embedded (FFPE) tissues obtained from autopsied human brains. Herein, we report that discrete compartmentalization of TH-labeled innervations occurs in the putamen, as in the caudate nucleus (CN), with a higher density of TH labeling in the matrix compared to the striosomes. Our results provide anatomical evidence to support the hypothesis that compartment-specific dysfunction of the striosome-matrix dopaminergic systems might contribute to the genesis of movement disorders.
Ryoma Morigaki, Ryosuke Miyamoto, Shinya Ohkita, Yoshifumi Mizobuchi, Hideo Mure, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Nuclear factor kappa b is under the control of dopamine signaling in the mouse striatum, Neurologia Medico-Chirurgica, 55, 305, 2016.
28.
Ryoma Morigaki and Satoshi Goto : Postsynaptic Density Protein 95 in the Striosome and Matrix Compartments of the Human Neostriatum., Frontiers in Neuroanatomy, 9, 154, 2015.
(要約)
The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as disks large homolog 4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.
Satoshi Goto, Ryoma Morigaki, Shinya Okita, Shinji Nagahiro and Ryuji Kaji : Development of a highly sensitive immunohistochemical method to detect neurochemical molecules in formalin-fixed and paraffin-embedded tissues from autopsied human brains., Frontiers in Neuroanatomy, 9, 22, 2015.
(要約)
Immunohistochemistry (IHC) is a valuable method for identifying discrete neurochemical molecules by the interaction of target antigens with validated antibodies tagged with a visible label (e.g., peroxidase). We have developed an immunostaining method that is highly sensitive in detection of neurochemical antigens. Our IHC method, which we call the PBTA method, involves a hybrid protocol that implements aspects of both the polymer and avidin-biotin-complex (ABC) methods in combination with biotin-tyramide amplification. When using [Met]-enkephalin as a target antigen, the sensitivity of the PBTA method for IHC was more than 100-fold higher compared with the polymer and ABC methods. In addition, its sensitivity for enzyme-linked immunosorbent assay was about 1,000-fold higher compared with the ABC method. We examined the utility of our IHC method for both chromogenic and fluorescence detection systems used to visualize neurochemical peptides and proteins in formalin-fixed, paraffin-embedded tissues from autopsied human brains. The results convincingly demonstrate that under optimal conditions, our IHC method is highly sensitive without increasing non-specific background activities. Our IHC method could be a powerful tool for detection and visualization of neurochemical antigens that are present even in trace amounts in autopsied human brains.
Hidetaka Koizumi, Satoshi Goto, Shinya Okita, Ryoma Morigaki, Norio Akaike, Yasushi Torii, Tetsuhiro Harakawa, Akihiro Ginnaga and Ryuji Kaji : Spinal Central Effects of Peripherally Applied Botulinum Neurotoxin A in Comparison between Its Subtypes A1 and A2., Frontiers in Neurology, 5, 98, 2014.
(要約)
Because of its unique ability to exert long-lasting synaptic transmission blockade, botulinum neurotoxin A (BoNT/A) is used to treat a wide variety of disorders involving peripheral nerve terminal hyperexcitability. However, it has been a matter of debate whether this toxin has central or peripheral sites of action. We employed a rat model in which BoNT/A1 or BoNT/A2 was unilaterally injected into the gastrocnemius muscle. On time-course measurements of compound muscle action potential (CMAP) amplitudes after injection of BoNT/A1 or BoNT/A2 at doses ranging from 1.7 to 13.6 U, CMAP amplitude for the ipsilateral hind leg was markedly decreased on the first day, and this muscle flaccidity persisted up to the 14th day. Of note, both BoNT/A1 and BoNT/A2 administrations also resulted in decreased CMAP amplitudes for the contralateral leg in a dose-dependent manner ranging from 1.7 to 13.6 U, and this muscle flaccidity increased until the fourth day and then slowly recovered. Immunohistochemical results revealed that BoNT/A-cleaved synaptosomal-associated protein of 25 kDa (SNAP-25) appeared in the bilateral ventral and dorsal horns 4 days after injection of BoNT/A1 (10 U) or BoNT/A2 (10 U), although there seemed to be a wider spread of BoNT/A-cleaved SNAP-25 associated with BoNT/A1 than BoNT/A2 in the contralateral spinal cord. This suggests that the catalytically active BoNT/A1 and BoNT/A2 were axonally transported via peripheral motor and sensory nerves to the spinal cord, where they spread through a transcytosis (cell-to-cell trafficking) mechanism. Our results provide evidence for the central effects of intramuscularly administered BoNT/A1 and BoNT/A2 in the spinal cord, and a new insight into the clinical effects of peripheral BoNT/A applications.
Akie Tanabe, Yukio Yamamura, Jiro Kasahara, Ryoma Morigaki, Ryuji Kaji and Satoshi Goto : A novel tyrosine kinase inhibitor AMN107 (nilotinib) normalizes striatal motor behaviors in a mouse model of Parkinson's disease., Frontiers in Cellular Neuroscience, 8, 50, 2014.
(要約)
Abnormal motor behaviors in Parkinson's disease (PD) result from striatal dysfunction due to an imbalance between dopamine and glutamate transmissions that are integrated by dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). c-Abelson tyrosine kinase (c-Abl) phosphorylates cyclin-dependent kinase 5 (Cdk5) at Tyr15 to increase the activity of Cdk5, which reduces the efficacy of dopaminergic signaling by phosphorylating DARPP-32 at Thr75 in the striatum. Here, we report that in the mouse striatum, a novel c-Abl inhibitor, nilotinib (AMN107), inhibits phosphorylation of both Cdk5 at Tyr15 and DARPP-32 at Thr75, which is negatively regulated by dopamine receptor activation through a D2 receptor-mediated mechanism. Like a D2-agonist, nilotinib synergizes with a D1-agonist for inducing striatal c-Fos expression. Moreover, systemic administration of nilotinib normalizes striatal motor behaviors in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These findings suggest that nilotinib could possibly serve as a new and alternative agent for treating PD motor symptoms.
Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Reversibility of ischemic findings on 3-tesla magnetic resonance T2(*)-weighted image after recanalization, The Journal of Medical Investigation : JMI, 61, 1,2, 190-196, 2014.
(要約)
Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.
Yuka Terasawa, Nobuaki Yamamoto, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Junichiro Satomi, Masafumi Harada, Shinji Nagahiro and Ryuji Kaji : Brush sign on 3-T t2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy, Stroke, 45, 1, 274-276, 2014.
(要約)
The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively (P=0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P=0.027). A good outcome (mRS, 0-1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group (P=0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4-59.8; P=0.022) was independently associated with hemorrhagic transformation. BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.
Hidetaka Koizumi, Ryoma Morigaki, Shinya Ohkita, Shinji Nagahiro, Masanori Nakagawa and Satoshi Goto : Response of striosomal opioid signaling to dopamine depletion in 6-hydroxydopamine-lesioned rat model of Parkinsons disease: a potential compensatory role, Frontiers in Cellular Neuroscience, 7, 74, 2013.
(要約)
The opioid peptide receptors consist of three major subclasses, namely, μ, δ, and κ (MOR, DOR, and KOR, respectively). They are involved in the regulation of striatal dopamine functions, and increased opioid transmissions are thought to play a compensatory role in altered functions of the basal ganglia in Parkinson's disease (PD). In this study, we used an immunohistochemistry with tyramide signal amplification (TSA) protocols to determine the distributional patterns of opioid receptors in the striosome-matrix systems of the rat striatum. As a most striking feature of striatal opioid anatomy, MORs are highly enriched in the striosomes and subcallosal streak. We also found that DORs are localized in a mosaic pattern in the dorsal striatum (caudate-putamen), with heightened labeling for DOR in the striosomes relative to the matrix compartment. In the 6-hydroxydopamine-lesioned rat model of PD, lesions of the nigrostriatal pathways caused a significant reduction of striatal labeling for both the MOR and DOR in the striosomes, but not in the matrix compartment. Our results suggest that the activities of the striosome and matrix compartments are differentially regulated by the opioid signals involving the MORs and DORs, and that the striosomes may be more responsive to opioid peptides (e.g., enkephalin) than the matrix compartment. Based on a model in which the striosome compartment regulates the striatal activity, we propose a potent compensatory role of striosomal opioid signaling under the conditions of the striatal dopamine depletion that occurs in PD.
Satoshi Goto, Toshitaka Kawarai, Ryoma Morigaki, Shinya Okita, Hidetaka Koizumi, Shinji Nagahiro, L Edwin Munoz, V Lillian Lee and Ryuji Kaji : Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism., Brain, 136, Pt 5, 1555-1567, 2013.
(要約)
Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.
Yukio Yamamura, Ryoma Morigaki, Jiro Kasahara, Hironori Yokoyama, Akie Tanabe, Shinya Ohkita, Hidetaka Koizumi, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice, Frontiers in Cellular Neuroscience, 7, 12, 1-10, 2013.
(要約)
Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.
Hiroyuki Ishiura, Wataru Sako, Mari Yoshida, Toshitaka Kawarai, Osamu Tanabe, Jun Goto, Yuji Takahashi, Hidetoshi Date, Jun Mitsui, Budrul Ahsan, Yaeko Ichikawa, Atsushi Iwata, Hiide Yoshino, Yuishin Izumi, Koji Fujita, Kouji Maeda, Satoshi Goto, Hidetaka Koizumi, Ryoma Morigaki, Masako Ikemura, Naoko Yamauchi, Shigeo Murayama, A Garth Nicholson, Hidefumi Ito, Gen Sobue, Masanori Nakagawa, Ryuji Kaji and Shoji Tsuji : The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement., American Journal of Human Genetics, 91, 2, 320-329, 2012.
(要約)
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal-dominant neurodegenerative disorder characterized by widespread fasciculations, proximal-predominant muscle weakness, and atrophy followed by distal sensory involvement. To date, large families affected by HMSN-P have been reported from two different regions in Japan. Linkage and haplotype analyses of two previously reported families and two new families with the use of high-density SNP arrays further defined the minimum candidate region of 3.3 Mb in chromosomal region 3q12. Exome sequencing showed an identical c.854C>T (p.Pro285Leu) mutation in the TRK-fused gene (TFG) in the four families. Detailed haplotype analysis suggested two independent origins of the mutation. Pathological studies of an autopsied patient revealed TFG- and ubiquitin-immunopositive cytoplasmic inclusions in the spinal and cortical motor neurons. Fragmentation of the Golgi apparatus, a frequent finding in amyotrophic lateral sclerosis, was also observed in the motor neurons with inclusion bodies. Moreover, TAR DNA-binding protein 43 kDa (TDP-43)-positive cytoplasmic inclusions were also demonstrated. In cultured cells expressing mutant TFG, cytoplasmic aggregation of TDP-43 was demonstrated. These findings indicate that formation of TFG-containing cytoplasmic inclusions and concomitant mislocalization of TDP-43 underlie motor neuron degeneration in HMSN-P. Pathological overlap of proteinopathies involving TFG and TDP-43 highlights a new pathway leading to motor neuron degeneration.
(キーワード)
Base Sequence / Chromosomes, Human, Pair 3 / DNA-Binding Proteins / Exome / Genetic Linkage / Genetic Predisposition to Disease / Golgi Apparatus / Haplotypes / Hereditary Sensory and Motor Neuropathy / Humans / Inclusion Bodies / 日本 (Japan) / Molecular Sequence Data / Motor Neurons / Pedigree / Point Mutation / Polymorphism, Single Nucleotide / Proteins / Sequence Analysis, DNA
Ryoma Morigaki, Kyong-Hon Pooh, Kenji Shouno, Hidekazu Taniguchi, Shouichi Endo and Yoshinobu Nakagawa : Choroid plexus papilloma in a girl with hypomelanosis of Ito., Journal of Neurosurgery. Pediatrics, 10, 3, 182-185, 2012.
(要約)
The authors report a case of choroid plexus papilloma in a girl with hypomelanosis of Ito, and they review the literature in brief. Hypomelanosis of Ito is a rare neurocutaneous syndrome characterized by cutaneous hypopigmented whorls, streaks, and patches along lines of Blaschko. Most patients exhibit CNS manifestations, including psychomotor retardation, seizures, hypotonia, and ataxia. A 6-year-old girl with hypomelanosis of Ito was referred to the authors' hospital with bilateral tumors in the lateral ventricles. The right lateral ventricle tumor was surgically removed. Immunohistochemical investigations revealed the tumor to be a choroid plexus papilloma (WHO Grade I). A chromosomal investigation revealed that the tumor tissue demonstrated a large loss of heterozygosity at chromosome 10. The case reported here serves as a reminder that de novo brain tumors may arise in patients with chromosomal mosaicism.
Ryosuke Miyamoto, Satoshi Goto, Wataru Sako, Ai Miyashiro, Isabelle Kim, Fabienne Escande, Masafumi Harada, Ryoma Morigaki, Koutaro Asanuma, Yoshifumi Mizobuchi, Shinji Nagahiro, Yuishin Izumi and Ryuji Kaji : Generalized dystonia in a patient with a novel mutation in the GLUD1 gene, Movement Disorders, 27, 9, 1198-1199, 2012.
Toshiyuki Okazaki, Teruyoshi Kageji, Kazuyuki Kuwamura, Keiko T. Kitazato, Hideo Mure, Keijiro Hara, Ryoma Morigaki, Yoshifumi Mizobuchi, Kazuhito Matsuzaki and Shinji Nagahiro : Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma, Cancer Letters, 323, 2, 199-207, 2012.
(要約)
Interferon-beta (IFN-) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN--induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.
Ryoma Morigaki, Junichiro Satomi, E Shikata and Shinji Nagahiro : Aneurysm of the lateral spinal artery: A case report, Clinical Neurology and Neurosurgery, 114, 713-716, 2012.
S Okita, Ryoma Morigaki, H Koizumi, Ryuji Kaji, Shinji Nagahiro and Satoshi Goto : Cell type-specific localization of optineurin in the striatal neurons of mice: Implications for neuronal vulnerability in huntington's disease, Neuroscience, 202, 27, 363-370, 2012.
(要約)
Striatal neuropathology of Huntington's disease (HD) involves primary and progressive degeneration of the medium-sized projection neurons, with relative sparing of the local circuit interneurons. The mechanism for such a patterned cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is one of the proteins interacting with huntingtin and plays a protective role in several neurodegenerative disorders. To determine the cellular localization pattern of OPTN in the mouse striatum, we employed a highly sensitive immunohistochemistry with the tyramide signal amplification system. In this study, we show that OPTN appeared as a cytoplasmic protein within the subsets of the striatal neurons. Of particular interest was that OPTN was abundantly expressed in the interneurons, whereas low levels of OPTN were observed in the medium projection neurons. This cell type-specific distribution of OPTN in the striatum is strikingly complementary to the pattern of neuronal loss typically observed in the striatum of patients with HD. We suggest that OPTN abundance is an important cellular factor in considering the cell type-specific vulnerability of striatal neurons in HD.
Ryoma Morigaki, Wataru Sako, Shinya Okita, Jiro Kasahara, Hironori Yokoyama, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Cyclin-dependent kinase 5 with phosphorylation of tyrosine 15 residue is enriched in striatal matrix compartment in adult mice, Neuroscience, 189, 25-31, 2011.
(要約)
Accumulating evidence suggests that the striosome-matrix systems have a tight link with motor and behavioral brain functions and their disorders. Cyclin-dependent kinase 5 (Cdk5) is a versatile protein kinase that plays a role in synaptic functions and cell survival in adult brain, and its kinase activity is stimulated by phosphorylation at tyrosine 15 residue (pY15). In this study, we used an immunohistochemical method to show differential localization of Cdk5-pY15 in the striatal compartments of adult mice, with a heightened density of Cdk5-pY15 labeling in the matrix relative to the striosomes. Our findings indicate that Cdk5-pY15 can be a new marker for the striatal matrix compartment, and suggest a possible involvement of Cdk5-mediated signaling in compartment-specific neurotransmission and disease pathology in the striatum.
Wataru Sako, Ryoma Morigaki, Ryuji Kaji, Ikuo Tooyama, Shinya Okita, Keiko Kitazato, Shinji Nagahiro, M Ann Graybiel and Satoshi Goto : Identification and localization of a neuron-specific isoform of TAF1 in rat brain: implications for neuropathology of DYT3 dystonia, Neuroscience, 189, 100-107, 2011.
(要約)
The neuron-specific isoform of the TAF1 gene (N-TAF1) is thought to be involved in the pathogenesis of DYT3 dystonia, which leads to progressive neurodegeneration in the striatum. To determine the expression pattern of N-TAF1 transcripts, we developed a specific monoclonal antibody against the N-TAF1 protein. Here we show that in the rat brain, N-TAF1 protein appears as a nuclear protein within subsets of neurons in multiple brain regions. Of particular interest is that in the striatum, the nuclei possessing N-TAF1 protein are largely within medium spiny neurons, and they are distributed preferentially, though not exclusively, in the striosome compartment. The compartmental preference and cell type-selective distribution of N-TAF1 protein in the striatum are strikingly similar to the patterns of neuronal loss in the striatum of DYT3 patients. Our findings suggest that the distribution of N-TAF1 protein could represent a key molecular characteristic contributing to the pattern of striatal degeneration in DYT3 dystonia.
(キーワード)
Amino Acid Sequence / Animals / Base Sequence / 脳 (brain) / Corpus Striatum / Dystonia / Histone Acetyltransferases / Molecular Sequence Data / Nuclear Proteins / Protein Isoforms / Rats / Rats, Sprague-Dawley / TATA-Binding Protein Associated Factors / Transcription Factor TFIID
Ryoma Morigaki, Kyong-Hon Pooh and Yoshinobu Nakagawa : Endoscopic transaqueductal placement of a single-catheter cyst-ventriculoperitoneal shunt in a neonate with Dandy-Walker malformation-associated hydrocephalus: case report., Neurologia Medico-Chirurgica, 51, 3, 256-259, 2011.
(要約)
A neonate with hydrocephalus associated with Dandy-Walker malformation was successfully treated with an endoscopic placement of a transaqueductal ventricular single catheter. The modified catheter was provided with additional fenestration on its proximal side to allow simultaneous drainage from both the supra- and infratentorial compartments. This technique is well known for isolated fourth ventricles, but has not been applied to hydrocephalus associated with Dandy-Walker malformation. The cyst-ventriculoperitoneal shunt effectively drained both compartments. The patient was doing well 18 months after the surgical procedure. Endoscopic transaqueductal shunt placement can be considered, especially in patients with aqueductal patency.
Wataru Sako, Ryoma Morigaki, Yoshifumi Mizobuchi, Takashi Tsuzuki, Hiroyuki Ima, Y Ushio, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Bilateral pallidal deep brain stimulation in primary Meige syndrome, Parkinsonism & Related Disorders, 17, 2, 123-125, 2011.
(要約)
Primary Meige syndrome is an idiopathic movement disorder that manifests as craniofacial and often cervical dystonias. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as a powerful surgical option in the treatment of primary generalized or segmental dystonia. However, the experience with GPi-DBS in Meige syndrome is limited. We followed 5 patients with disabling Meige syndrome treated by bilateral GPi-DBS for 49 ± 43.7 (mean ± SD) months. All patients were assessed before surgery and at the last follow-up after surgery using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) which includes both the movement and disability scales. Bilateral GPi-DBS produced a sustained and long-lasting improvement in dystonia symptoms associated with Meige syndrome. At the last follow-up, the mean scores of BFMDRS movement and disability scales improved significantly by 84 ± 6.8% (range, 75-94%) and 89 ± 8.1% (range, 80-100%), respectively. Bilateral pallidal stimulation is a beneficial therapeutic option for long-term relief of the disabling dystonia symptoms in Meige syndrome.
Ryoma Morigaki, Kiyohito Shinno, Kyong-Hon Pooh and Yoshinobu Nakagawa : Giant glioependymal cyst in an infant., Journal of Neurosurgery. Pediatrics, 7, 2, 175-178, 2011.
(要約)
The authors report the case of an infant with a giant glioependymal cyst. Although it has been suggested that these cysts originate from the tela choroidea, their origin remains controversial. This 35-month-old girl with truncal ataxia was referred to the authors' hospital. Magnetic resonance imaging revealed a giant cystic mass extending from the anterior to the posterior cranial fossa. Hydrocephalus was caused by obstruction of the sylvian aqueduct. Endoscopic fenestration of the cyst wall was performed. Histochemical and immunohistochemical staining identified the lesion as a glioependymal cyst. Magnetic resonance imaging performed 8 months later suggested that the cyst originated from the tela choroidea. At 5-year follow-up, there was no tumor recurrence and she had fully recovered. The origin of glioependymal cysts is discussed, and the authors suggest that their origin is the tela choroidea.
(キーワード)
Brain Diseases / Central Nervous System Cysts / Child, Preschool / Ependyma / Female / Humans
Wataru Sako, Ryoma Morigaki, Shinji Nagahiro, Ryuji Kaji and Satoshi Goto : Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice, Neuroscience, 170, 2, 497-502, 2010.
(要約)
There is a growing body of evidence that striosome-matrix dopamine systems are tightly linked with motor and behavioral brain functions and disorders. In this study, we used an immunohistochemical method to show differential expression of the olfactory type G-protein alpha subunit (Galphaolf) that involves in the coupling of dopamine D1 receptor with adenylyl cyclase in the striatal compartments of adult mice, and observed heightened density of Galphaolf labeling in the striosomes relative to the matrix compartment. Our findings suggest that Galphaolf could be one of the key molecules for controlling differential responses of the striosome and matrix compartments to dopamine D1 receptor signaling in the striatum of adult mice.
(キーワード)
Animals / Apomorphine / Corpus Striatum / Dopamine / Dopamine and cAMP-Regulated Phosphoprotein 32 / GTP-Binding Protein alpha Subunits / Mice / Neurons / Receptors, Dopamine D1 / Receptors, Opioid, mu / Signal Transduction / Tyrosine 3-Monooxygenase
Ryoma Morigaki, Masaaki Uno, Atsuhiko Suzue and Shinji Nagahiro : Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis. Report of two cases., Journal of Neurosurgery, 105, 1, 142-147, 2006.
(要約)
In this paper the authors describe two patients with recurrent hemiparesis and limb shaking that gradually progressed to hemichorea. Cerebral angiography confirmed severe unilateral internal carotid artery stenosis (95%) contralateral to the hemichorea. The cerebral blood flow, assessed using N-isopropyl-p-(iodine-123) iodoamphetamine single-photon emission computed tomography (SPECT), disclosed markedly decreased vascular reserves in both patients. After carotid endarterectomy was performed, the hemichorea gradually subsided and SPECT confirmed increased cerebral perfusion. The results in these cases indicate that surgical revascularization is effective for hemichorea due to cerebral ischemia with reduced vascular reserve.
S Kudo, Ryoma Morigaki, J Saito, M Ikeda, K Oka and K Tanishita : Shear-stress effect on mitochondrial membrane potential and albumin uptake in cultured endothelial cells., Biochemical and Biophysical Research Communications, 270, 2, 616-621, 2000.
(要約)
Endothelial cells (ECs) that line the inner surface of blood vessels are continuously exposed to shear stress induced by blood flow in vivo, and shear stress affects ATP-dependent macromolecular transport in ECs. However, the relationship between the ATP production and shear stress is still unclear. We, therefore, evaluated mitochondrial ATP synthesis activity in cultured endothelial cells exposed to shear stress, using a confocal laser scanning microscope (CLSM) and a mitochondrial membrane potential probe (5,5',6,6'-tetrachloro-1,1',3, 3'-tetraethyl-benzimidazolycarbocyanine iodide, JC-1). Low shear stress (10 dyn/cm(2)) increased mitochondrial membrane potential by 30%. On the contrary, high shear stress (60 dyn/cm(2)) decreased it by 20%. This observation was consistent with the ATP-dependent albumin uptake into endothelial cells. Our results indicate that ATP synthetic activity is related to the albumin uptake into endothelial cells.
We assessed the efficiency of pallidal deep brain stimulation for tardive dystonia. This search was carried out in Electronic chart of Tokushima University Hospital. 5 patients with tardive dystonia were enrolled. GPi(internal segment of globus pallidus)was the target in all patients. The motor part of Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS)was improved by 78．4% on average when compared to preoperative BFMDRS scores. The performed analysis indicates that GPi-DBS is an effective and safe treatment for tardive dystonia.
Ryoma Morigaki, Masahito Nakataki, Toshitaka Kawarai, Lillian V. Lee, Rosalia A. Teleg, Ma Daisy P. Tabuena, Hideo Mure, Wataru Sako, Paul Matthew D. Pasco, Shinji Nagahiro, Junichi Iga, Tetsuro Ohmori, Satoshi Goto and Ryuji Kaji : Depression in X-linked dystonia-parkinsonism:A case-control study, Parkinsonism & Related Disorders, 19, 9, 844-846, 2013.
Ryoma Morigaki and Ryosuke Miyamoto : Dystonia: Still a Mysterious Syndrome., Life, 12, 7, Jul. 2022.
(要約)
The diagnosis of dystonia is sometimes complicated due to its many clinical manifestations, causes, and the lack of specific diagnostic examinations or simple algorithms [...].
Ryoma Morigaki and Satoshi Goto : A short commentary on globus pallidus internus deep brain stimulation in primary Meige syndrome, Journal of Neurology & Neurophysiology, 7, 6, 2016.
Taku Matsuda, Ryoma Morigaki, Hiroaki Hayasawa, Hiroshi Koyama, Teruo Oda, Kazuhisa Miyake and Yasushi Takagi : Striatal parvalbumin interneurons, not cholinergic interneurons, are activated in a mouse model of cerebellar dystonia, NEURO2024, Fukuoka, Jul. 2024.
2.
Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto and Yasushi Takagi : Cranial geometry in patients with dystonia, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
3.
NAKANISHI Hiroshi, Ryoma Morigaki, Nobuaki Yamamoto, Joji Fujikawa, Teruo Oda, OMAE Hiroshi, Yuishin Izumi and Yasushi Takagi : The effect of Rikaba, a hybrid physical exercise salon for Parkinson's disease patients, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
4.
Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama and Yasushi Takagi : Long-term follow-up of 12 patients treated with bilateral pallidal stimulation for tardive dystonia, 13th Scientific meeting of Asian Australasian Society for Streotactic and Functional Neurosurgery, Osaka, Apr. 2023.
5.
OMAE Hiroshi, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, 中野渡 友香, Megumi Kuno, Tetsuya Matsuura and Yasushi Takagi : Cognitive changes due to subthalamic nucleus deep brain stimulation in elderly Parkinson's Disease, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
6.
Ryoma Morigaki, Maya Anzai, Joji Fujikawa, Teruo Oda, Hayasawa Hiroaki, Matsuda Taku, Jiro Kasahara and Yasushi Takagi : Changes in phosphodiesterase 10A in mice model of levodopa-induced dyskinesia, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
7.
Harumi Kadota, Shoma Fujisawa, Masaki Oono, Ryoma Morigaki, Nobuaki Yamamoto, Yasuhisa Kanematsu, Manabu Ishihara and Masami Shishibori : Development of a 3D visualization system for the cerebral aneurysm coil embolization, Proceedings Volume 11794, Fifteenth International Conference on Quality Control by Artificial Vision; 117940C (2021), Tokushima, Jul. 2021.
Ryoma Morigaki, Masatoshi Ogawa, Shinya Ohkita, Taku Matsuda, Yasushi Takagi and Satoshi Goto : Phospho-serine 276 of nuclear factor kappa b is involved in the genesis of l-dopa-induced dyskinesia, The Journal of Neuroscience, 2021.
9.
Ryoma Morigaki, Lee H Janifer, Yoshida Tomoko, Wuthrich Christian and Graybiel M Ann : Mu opioid receptors are strongly upregulated in the q175 mouse model of huntingtons disease, The Journal of Neuroscience, Chicago, IL, Oct. 2019.
10.
Ryoma Morigaki, S Okita, Hideo Mure, Yasushi Takagi and S Goto : Olfactory type g-protein alfa subunit related changes in the striatum underlie the genesis of L-DOPA induced dyskinesiaBrain and Brain PET2019, Brain and Brain PET2019, Jul. 2019.
11.
Ryoma Morigaki, Shinya Ohkita, Hideo Mure, Yasushi Takagi and Satoshi Goto : Olfactory type G-protein alfa subunit related changes in the striatum underlie the genesis of L-dopa-induced dyskinesia, Journal of Cerebral Blood Flow and Metabolism, Yokohama, Jun. 2019.
12.
Hideo Mure, Ryoma Morigaki, Shinya Ohkita, Ryosuke Miyamoto, Shinji Nagahiro and Satoshi Goto : Deep Brain Stimulation for Dystonia - Pallidal stimulation and thalamic stimulation, World Society for Stereotactic and Functional Neurosurgery, Berlin, Jun. 2017.
13.
Toshitaka Kawarai, Ryosuke Miyamoto, Hideo Mure, Ryoma Morigaki, Orlacchio Antonio, Koichihara Reiko, Nakagawa Eiji, Takashi Sakamoto, Yuishin Izumi, Satoshi Goto and Ryuji Kaji : Haploinsufficiency of KMT2B causes myoclonus-dystonia with impaired psychomotor ability, The MDS 21th International Congress of Parkinsons Disease and Movement Disorders, Jun. 2017.
(キーワード)
KMT2B / dystonia
14.
Jiro Kasahara, Yamamura Yukio, Tanabe Akie, Ryoma Morigaki, Ryuji Kaji and Satoshi Goto : Inhibition of c-Abelson tyrosine kinase (c-Abl) as a possible strategy for treatment of PD: Study in MPTP-induced mice model, The 12th International Conference on Alzheimers's and Parkinson;s Disease: AD/PD 2015, Mar. 2015.
15.
Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Ryoma Morigaki, Koji Fujita, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro and Ryuji Kaji : Reversibility of ischemic findings on 3-tesla magnetic resonance T2*-weighted image after recanalization, European Stroke Conference 2014, Nice, France, May 2014.
16.
Yoshifumi Mizobuchi, T Okazaki, Teruyoshi Kageji, Kazuyuki Kuwayama, KT Kitazato, Hideo Mure, Keijiro Hara, Ryoma Morigaki, Kazuhito Matsuzaki, Kohhei Nakajima, T Fujihara and Shinji Nagahiro : A combination of interferon-beta and temozolomide augments anti-tumor effects through p73/YAP-mediated apoptosis by PML in glioblastoma, The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology held in conjunction with the 2013 SNO Scientific Meeting and Education Day, San Francisco, Nov. 2013.
17.
Junichiro Satomi, Shinji Nagahiro, Shunji Matsubara, Masaaki Uno, Koichi Satoh, Norio Nakajima, Kohhei Nakajima, Kyoko Nishi and Ryoma Morigaki : Combined treatment for intracranial giant aneurysms, 9th International Conference on Cerebrovascular Surgery, Nagoya, Nov. 2009.
Toshitaka Kawarai, Mitsuya Morita, Ryoma Morigaki, Koji Fujita, Hiroyuki Nodera, Yuishin Izumi, Satoshi Goto, Imaharu Nakano and Ryuji Kaji : Pathomechanisms of motor neuron death by mutant TFG., Clinical Neurology, 23, 11, 1199, 2013.
(要約)
Mutations in TFG gene have been demonstrated in hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) and hereditary spastic paraplegia (HSP). A broad spectrum of TFG pathology is suspected in motor neuron diseases including amyotrophic lateral sclerosis (ALS). We performed mutation screening of TFG gene in ALS cases and evaluated the biological functions of mutant TFG by expression experiment in cultured cells. Two missense mutations associated with sporadic ALS were discovered. Mislocalization of ALS-related proteins, including TDP-43 and optineurin, was demonstrated. These results indicate that mistrafficking of ALS-related proteins by mutant TFG might be a biological cascade leading to motor neuron death.