著者

神林 崇 今西 彩 石戸 秀明 大森 佑貴 富永 杜絵 小野 太輔 西野 精治 近藤 英明

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.6, pp.S139, 2020 (Released:2020-10-05)

著者

兼子 幸一

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.33, no.5, pp.S136, 2016 (Released:2016-10-31)

著者

鈴木 重明

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.4, pp.526-530, 2020 (Released:2021-05-27)

参考文献数

41

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Neuromuscular adverse events (AEs) associated with cancer treatment with immune checkpoint inhibitors (ICIs) include diverse clinical subsets. The general features of neuromuscular AEs have not been elucidated because the frequency is generally low, ranging from 1%–2% of cancer patients undergoing ICIs therapy. The diseases affect the central nervous system, peripheral nerves, neuromuscular junction, and muscle. Disease onset and progression may be rapid with a critical clinical course. The clinical presentation may be different from that of patients unrelated to drugs. Headache, dizziness, and dysgeusia were relatively common and mild treatment–related AEs. In contrast, representative immune–related AEs such as autoimmune encephalitis, demyelinating polyneuropathy, myasthenia, and myositis were serious. There was a tight association between myasthenia, myositis, and myocarditis. There are guidelines for the treatment of neuromuscular immune–mediated AEs. For all but the minimum neurological symptoms, checkpoint inhibitor therapy should be withheld until the nature of the AEs is defined. Immune–modulating medication is generally effective for neuromuscular AEs. Both CD8+ cytotoxic T–cells and autoantibodies are involved in the pathogenesis of neuromuscular AEs. Correct understanding of neuromuscular AEs is required for the best management of cancer patients.

著者

髙嶋 博

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.35, no.6, pp.S105, 2018 (Released:2018-11-12)

著者

久保田 暁

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.2, pp.129-134, 2020 (Released:2020-08-31)

参考文献数

21

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Polymyositis (PM) has been a common clinical diagnosis for inflammatory myopathies without dermatitis, since Bohan and Peter established diagnostic criteria classifying polymyositis and dermatomyositis by the presence of dermatitis. In Japan, the diagnostic criteria of polymyositis and dermatomyositis for medical subsidies are also based on the presence of dermatitis, and there are a number of patients with “polymyositis”. However, clinical, pathological, and serological studies have revealed that the inflammatory myopathies without dermatitis are a heterogenous group, including sporadic inclusion body myositis (sIBM), immune–mediated necrotizing myopathy (IMNM), collagen disease related myositis, and PM. For adequate clinical decisions as well as high–quality studies, PM should be diagnosed based on strict diagnostic criteria including pathological examination, such as the European Neuromuscular Centre (ENMC) criteria. Among 972 cases that had been diagnosed as inflammatory myopathies in our laboratory between 2000 and 2019, about 2/3 cases (550/925) lacked dermatitis, and could be diagnosed as “polymyositis” by Bohan and Peter criteria. However, based on the ENMC criteria, only 1.7% (17/972) cases were classified as PM. Even after the diagnosis of PM was made by pathological examination, some patients may be reclassified as other diseases, especially as sIBM. The improvement of pathological examination further reduced the number of misdiagnosed “PM”. In addition, infiltration of CD8 positive cells surrounding non–necrotic fibers, a hallmark of PM and sIBM, is also observed in other myopathies. Some researchers doubt the existence of PM. Thus, PM is a shrinking entity.

著者

榊原 隆次

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.34, no.4, pp.412-417, 2018 (Released:2018-02-20)

参考文献数

24

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Parkinson's disease (PD) is a common neurodegenerative disorder, and lower urinary tract (LUT) dysfunction is one of the most common autonomic disorders, and nocturia is the major LUTS in PD with an estimated incidence rate of 70%. We review the pathophysiology of bladder dysfunction in PD, lower urinary tract symptoms (LUTS), objective assessment, and treatment options. In patients with PD, disruption of the dopamine D1–GABAergic direct pathway may lead to LUTS. Overactive bladder (OAB) is the most common LUT symptom in PD patients, and an objective assessment using urodynamics commonly shows detrusor overactivity (DO) in these patients. The post–void residual (PVR) volume is minimal in PD, which differs significantly from multiple system atrophy (MSA) patients who have a more progressive disease that leads to urinary retention. However, subclinical detrusor weakness during voiding may also occur in PD. Regarding bladder management, there are no large, double–blind, prospective studies in this area. It is well recognised that dopaminergic drugs can improve or worsen LUTS in PD patients. Therefore, an add–on therapy with anticholinergics is required. Beta–3 adrenergic agonists are a potential treatment option because there are little to no central cognitive events. Newer interventions, such as deep brain stimulation (DBS), are expected to improve bladder dysfunction in PD. Botulinum toxin injections can be used to treat intractable urinary incontinence in PD. Transurethral resection of the prostate gland (TURP) for comorbid BPH in PD is now recognised to be not contraindicated if MSA is excluded. Collaboration of urologists with neurologists is highly recommended to maximise a patients' bladder–associated QOL.

著者

深沢 良輔 西村 優佑 武澤 秀理 藤井 明弘

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.38, no.5, pp.757-760, 2021 (Released:2022-05-31)

参考文献数

9

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16歳女性.発熱,頭痛が出現した2週間後より変動する意識障害,独語,従命不良が出現した.頭部MRIで異常なく,卵巣腫瘍の合併はなかった.経過から腫瘍非合併の抗n–methyl–D–aspartate(NMDA)受容体脳炎と考え,ステロイドパルス,単純血漿交換,免疫グロブリン静注療法,免疫抑制薬を併用した集学的免疫療法を実施した.最重症時は挿管,ICU管理が必要な状態まで増悪がみられたが,早期より各免疫療法を繰り返し行ったことで,意識障害の出現から2か月程度の経過で機能予後良好なレベルまで症状改善が得られた.抗NMDA受容体脳炎の長期予後調査で81%は24か月後の機能予後良好(modified Rankin Scale:mRS 0–2)と報告されたが,回復するまでに時間を要することが示されている.抗NMDA受容体脳炎において早期の積極的な集学的免疫療法が奏効する可能性が示唆された.

著者

山脇 健盛

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.38, no.2, pp.86-91, 2021 (Released:2021-10-05)

参考文献数

35

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Superficial siderosis (SS) is a rare condition in which hemosiderin is deposited on the pial surface of the brain and/or spinal cord. It is supposed that hemosiderin deposition is a result of recurrent or persistent hemorrhage in the subarachnoid space. There are two types of SS. One is a “classical type”, in which low intensity of MRI is diffuse and symmetrical in brainstem and cerebellum. Patients with classical SS usually reveal slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, myelopathy and/or cognitive decline due to involvement of the acoustic nerve, cerebellum, spinal cord and/or cerebral cortex. The other is a “localized (cortical) type”, in which low intensity of MRI is localized in cerebral cortex without infratentorial involvement. The most common causes of hemorrhage in “localized type” are cerebral amyloid angiopathy and/or Alzheimer's disease.

著者

德丸 阿耶

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.38, no.4, pp.514-519, 2021 (Released:2022-04-28)

参考文献数

13

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Among neurodegenerative diseases, “What kind of disease should we know now?” is the theme given to me at the 38th Annual Meeting of the Japanese Society of Neurological Therapeutics. In recent years, neuroimaging have been actively incorporated as objective biomarkers into diagnostic criteria for neurodegenerative diseases, and there are a wide variety of issues to be addressed. In this paper, in the limited space, the characteristic MRI findings of diffusion–enhanced images trigger the diagnosis of intranuclear inclusion disease, hereditary diffuse leukoencephalopathy with axonal spheroids–CSF1R and their differential diagnoses. In addition, as the development of Alzheimer's disease modifiers progresses, it is important to distinguish diseases other than Alzheimer's disease, which develop due to forgetfulness and show the first imaging findings of hippocampal atrophy. I will describe argyrophilic grain disease/dementia of grains (AGD/DG), primary age–related tauopathy (PART), limbic–predominant age–related TDP–43 encephalopathy (LATE) and their differential diagnoses, and hope that it would be a useful step for the treatment of neurodegenerative diseases in the near future.

著者

平野 照之

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.34, no.1, pp.3-7, 2017 (Released:2017-05-31)

参考文献数

32

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Thrombolytic therapy for acute ischemic stroke was established in 1995, when the National Institutes of Neurological Disorders and Stroke recombinant tissue–type Plasminogen Activator Stroke Study (NINDS rt–PA stroke study) group revealed the efficacy of intravenous alteplase infusion at 0.9mg/kg. The drug, alteplase, was introduced to Japan in 2005 after Japan Alteplase Clinical Trial (J–ACT) showed identical efficacy and safety to NINDS study using a reduced dose of 0.6mg/kg. The time allowance for the use of the drug was extended from 3 hours to 4.5 hours in 2012 in Japan. This therapy is still being investigating in several ways : 1) Optimal dosing, 0.6mg/kg vs. 0.9mg/kg, was investigated on the Enhanced Control of Hypertension and Thrombolysis Stroke Study, 2) extending time window over 4.5 hours using advanced brain imaging, 3) Introduction of mobile stroke unit that enables field administration, 4) Developing new–generation thrombolytic drugs that have more fibrin specificity, better plasminogen activator inhibitor resistance and longer half–life than alteplase.Streptokinase, alteplase, duteplase, desmoteplase, and tenecteplase are the previously or currently tested drugs as for the use of acute thrombolytic therapy. Among them, alteplase is the only drug approved to use in clinical settings. Other drugs except for tenecteplase were failed to proceed to clinical application. Tenecteplase is currently the only drug that has possibility to replace alteplase in the future. Several phase III studies comparing tenecteplase with alteplase are currently ongoing. In Japan, however, tenecteplase is officially not available currently, even for acute myocardial infarction. The most advanced study, Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE), is targeting more than 1,000 stroke patients who have targeted mismatch on advanced brain imaging within 4.5 hours. Should tenecteplase proved better efficacy and safety over alteplase, international standard drug will be replaced to tenecteplase.

著者

石川 晴美

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.36, no.3, pp.265-267, 2019 (Released:2019-11-25)

参考文献数

8

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Herpes simplex virus encephalitis may have a relapsing course in up to 13–24% of adults and children, despite antiviral treatment. Herpes simplex encephalitis can trigger autoimmune encephalitis that leads to neurological worsening. This review will recapitulate the recent scientific progress.

著者

川本 未知

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.38, no.6, pp.S129, 2021 (Released:2021-10-10)

著者

西田 陽一郎 横田 隆徳

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.34, no.3, pp.258-261, 2017 (Released:2017-10-14)

参考文献数

9

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Nucleic acid medicine treatment is a promising technology and improving the efficacy of therapeutic oligonucleotides is still needed for its broad use. Although antisense oligonucleotides (ASOs) and short interfering RNA (siRNA) have been well known as nucleic acid medicine, pharmaceutical developments by using them are not completely free to be done due to patent protection. Therefore, we developed a new technology, third generation oligonucleotide. We named it heteroduplex oligonucleotide (HDO). In addition, our original drug delivery system (DDS) using glucose trasporter–1 (GLUT1) made great enhancement on delivery of oligonucleotides into the brain through blood–brain barrier (BBB). In this symposium, we show above two new technologies we have developed, and outline the nucleic acid medicine treatment for amyotrophic lateral sclerosis (ALS).

著者

脇田 英明 冨本 秀和

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.34, no.5, pp.491-494, 2018 (Released:2018-04-05)

参考文献数

10

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Dementia affects over 35 million people in the world with a rapidly increasing prevalence. Alzheimer's disease (AD) is the most common form of dementia. No fundamental treatment for AD has been established, and novel therapeutic strategies are under investigation. This progress has led to the development of numerous therapeutic strategies in the clinical testing. Immunotherapy against Aβ has been pursued extensively as a therapeutic approach to Alzheimer's disease, and several other promising trials are currently ongoing. In addition, new therapeutic strategies have been reported in Huntington's disease and frontotemporal dementia. This review overviews recent advances in basic and clinical research in dementia.

著者

西條 政幸

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.4, pp.648-652, 2020 (Released:2021-05-27)

参考文献数

23

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Severe fever with thrombocytopenia syndrome (SFTS) was first discovered as an emerging virus infection caused by a novel bunyavirus, which is classified to the Banyangvirus Genus in the Phenuiviridae Family (Huaiyangshan banyangvirus, former SFTS virus, SFTSV) in 2011. SFTS was also reported to be endemic not only to China, but also to Japan, South Korea, Vietnam, and Taiwan. The major symptoms of SFTS are gastrointestinal symptoms such as fever, general fatigue, nausea, vomiting, and diarrhea. Total blood cell counts revealed thrombocytopenia and leukopenia in patients with SFTS. Approximately seven years have passed since the discovery of SFTS patient in Japan. Forty to 100 patients with SFTS have been reported annually to the National Institute of Infectious Diseases from western part of Japan. Case fatality rate of SFTS is approximately 27–31%. The reasons behind the high case fatality rate might be that multiorgan failure, coagulopathy, and hemophagochtosis are induced in most SFTS patients. It was reported that an antiviral drug, favipiravir, was effective in the treatment of SFTSV infection in an animal infection model. SFTSV is circulating between wild animals and several species of ticks in nature, indicating that we cannot escape the risk of being infected with SFTSV and that SFTS will continue to occur in the endemic areas. Furthermore, it has been revealed that humans can also be infected with SFTSV through close contact with sick animals such as cats and dogs, both of which were also infected with SFTSV. Development of specific treatment and preventive measures with SFTS vaccines is necessary.

著者

濱口 浩敏

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.4, pp.543-547, 2020 (Released:2021-05-27)

参考文献数

5

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Deep vein thrombosis (DVT) is a condition in which a blood clot forms in a vein, usually in the legs or pelvis. When DVT occurs, urgent care is required. Here, we describe the diagnosis and treatment of DVT in patients with neurological disease.Stroke and DVTPatients with stroke may lose the ability to maintain a sitting position, stand, or walk due to sudden hemiplegia or quadriplegia. They may be forced to remain in bed during the acute period, which can make them more susceptible to the development of DVT in the leg on the affected side. Anticoagulant therapy may also lead to the concurrent prevention of DVT depending on the type of cerebral infarction, especially in cases of cardiogenic cerebral embolism, and care is taken in the selection and dosage of the anticoagulant.Cerebral infarction from DVTIt is important to understand that DVT can cause cerebral infarction. Emboli are sometimes produced in the cerebral arteries when there is a right–to–left shunt due to the existence of a patent foramen ovale, interatrial septal aneurysm, pulmonary arteriovenous fistula, or other condition. During diagnosis, the presence of a right–to–left shunt is confirmed with transesophageal echocardiography.Other neurological diseases and DVTThe frequency of DVT also increases in conditions where lower limb paralysis is seen, such as peripheral neuropathy or neurodegenerative disease. Unlike stroke, the onset is not sudden and the progressive nature makes the initial determination difficult. DVT can occur due to decreased physical activity from staying in bed or lower limb paralysis cause by secondary impairment to venous return. Consequently, regular evaluation and prevention of DVT is important in patients with neurological disease who have paralysis.ConclusionEarly discovery of DVT and appropriate treatment are important in patients with neurological disease.

著者

織茂 智之

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.4, pp.614-619, 2020 (Released:2021-05-27)

参考文献数

50

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In Lewy body disease including Parkinson's disease and dementia with Lewy bodies (DLB), dopamine neurons in the substantia nigra and various neurons in the brain degenerate, resulting in the appearance of motor and various non–motor symptoms. Lewy bodies are observed in the remaining neurons of the brain, which play an important role in neuronal degeneration. After that, there has been accumulating evidence that Lewy bodies are found in neurons of the peripheral autonomic system, resulting in the appearance of various autonomic symptoms. Cardiac meta–iodobenzylguanidine (MIBG) uptake on 123I–MIBG myocardial scintigraphy is reduced in patients with Lewy body disease, suggesting disturbance of the postganglionic sympathetic nerve in Lewy body disease. Postmortem studies have shown that the number of tyrosine hydroxylase–immunoreactive nerve fibers of the heart was decreased in pathologically–confirmed Lewy body disease, supporting the findings of the reduced cardiac MIBG uptake in Lewy body diseases. These clinical and pathological evidence have confirmed the involvement of the peripheral autonomic nervous system in Lewy body disease. Thus, the concept of “Lewy body disease is a systemic disease” has been established.

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.37, no.1, pp.61-104, 2020 (Released:2020-07-21)

著者

髙橋 愼一

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.35, no.3, pp.163-166, 2018 (Released:2018-12-25)

参考文献数

26

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The neurovascular unit (NVU) is a conceptual framework used to better understand the normal physiological interaction between neurons and microvessels as well as the pathophysiology of cerebral ischemia. The major components of the NVU consist of neurons, microvessels, and astrocytes that are interposed between the neuronal synapse and the microvasculature. In addition, other types of glial cells (microglia and oligodendroglia), pericytes, and the extracellular matrix (ECM) play important roles in the neurovascular coupling that enables microvessels to supply adequate glucose and oxygen to neurons when activated. The close proximity of microvessels to astroglial end–feet and the metabolic support of astrocytes for neurons suggest that communication could also be directed from microvessels to the neurons. Regarding alternative energy substrates other than glucose, the highly active astroglial glycolytic pathway provides neurons with lactate as a TCA cycle substrate. In addition, ketone bodies are thought to be generated mainly in astroglia to fuel neurons. The shunt pathway of glycolysis, the pentose–phosphate pathway, plays a pivotal role in the maintenance of NADPH, which that is necessary to protect both neurons and microvessels against reactive oxygen species (ROS). In fact, ROS induces neuronal pyruvate dehydrogenase complex (PDHC) dysfunction and ECM degradation, leading to hemorrhagic transformation after reperfusion. Astrocyte–derived ketone bodies can be utilized by the neuronal TCA cycle even after ischemic insult, since PDHC is not required for their metabolism. The concept of the NVU has expanded our understanding of pathophysiology and aided the development of novel therapeutic strategies against neurodegenerative diseases, neuro–immunological disorders, and stroke.

著者

清水 利彦

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.35, no.3, pp.295-297, 2018 (Released:2018-12-25)

参考文献数

15

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Migraine is a most common neurological disease that affects nearly 10% of the general population. However, the pathophysiology of migraine is obscure. Previously, it was believed that the pathophysiology of migraine could be explained entirely by the vascular theory, which is that all symptoms including aura of migraine and headache are caused by abnormal vascular responses. However, many subsequent researches have revealed that it is not possible to explain the symptoms of migraine only by abnormal vascular responses. Instead, functional abnormalities of the neuronal activities observed in the cortical spreading depression are thought to be also involved in the pathophysiology of migraine. Furthermore, it is reported the changes of functional connectivity in cerebral pain matrix system and functional abnormality of descending pain inhibitory system in migraine patients. In addition, it is also believed that the sensitization of the trigeminovascular neurons play an important roles in migraine pathophysiology. The present review discusses the recent findings of migraine pathophysiology.