著者

二村 明徳

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.40, no.6, pp.S172, 2023 (Released:2023-10-30)

著者

亀井 聡

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.39, no.3, pp.327-331, 2022 (Released:2022-11-22)

参考文献数

23

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NMDA receptor encephalitis is a common autoimmune encephalitis characterized by complex neuropsychiatric features and the presence of IgG antibodies against the NR1 subunit of the NMDA receptors in the central nervous system. This encephalitis start with flu–like symptoms, followed by fairly rapid development of psychiatric symptoms, memory problems, movement disorders, seizures, coma and even changes in heart rate, blood pressure. Based on the clinical analysis of 1147 patients, although there is a difference in severity, 90% of patients presented a similar clinical course. On the other, recent researches discovered that the clinical picture is widespread and it is known to present as a psychiatric disorder (autoimmune psychosis), temporal lobe adult–onset seizure (autoimmune epilepsy), and progressive dementia (autoimmune dementia). In the treatment of this encephalitis, the development has been showed in the treatment of refractory cases (such as Tocilizumab or Bortezomib) and symptomatic epilepsy.

著者

伊東 大介

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.39, no.3, pp.379-383, 2022 (Released:2022-11-22)

参考文献数

22

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The approval of amyloid β–targeted therapy for Alzheimer disease (AD) in the United States has opened the door for disease–modifying drugs for protinopathies. However, the target of treatment is mild cognitive impairment and/or mild Alzheimer disease (AD), but not advanced AD, and its efficacy is limited. Therefore, there is no doubt about the importance of establishing a therapeutic strategy for tau protein, another pathological indicator of AD. Tau is an accumulation protein that is pathologically correlated with the severity of dementia, and it has been considered as a key molecule that directly leads to neurodegeneration. Therefore, control of tau lesions is the essential therapeutic target in symptomatic AD.Immunotherapy and nucleic acid therapies are being developed as disease modifying agents for protinopathies. In particular, several clinical trials are underway for tau–targeted antibodies and antisense oligonucleotides. In this article, we will discuss the current status and prospects of disease–modifying drugs against tauopathies.

著者

下畑 享良

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.1, pp.20-23, 2021 (Released:2021-07-28)

参考文献数

15

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Coronavirus disease 2019 (COVID–19) associated with SARS–CoV–2 virus infection is often associated with neuromuscular symptoms, although it is mainly characterized by respiratory symptoms. In this article, I present movement disorders associated with COVID–19 including myoclonus, tremor, parkinsonism, and ataxia. These findings are presumed to be caused by immune–mediated pathogenesis after infection. Because the reports on the effects of COVID–19 in the treatment of neurodegenerative diseases are almost limited to Parkinson's disease, the effects of COVID–19 on the motor and non–motor symptoms of Parkinson's disease and some important points to consider in clinical practice are presented.

著者

田中 惠子

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.40, no.3, pp.227-231, 2023 (Released:2023-08-21)

参考文献数

31

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Newly identified autoantibodies in relation with autoimmune encephalitis have enabled the reclassification of diseases in neurology and psychiatry and its clinical scope has steadily grown. Many of them present with psychosis, memory disturbances, seizures, and movement disorders. Detection of disease–specific autoantibodies is useful for proper diagnosis and not missing immune therapy. Also, characterizing these antibody–binding antigens offer opportunities to investigate underlying pathogenesis of neurological features and understand general mechanisms of autoimmunity. However, the number of autoantibodies is increasing, which makes it difficult to use them as a diagnostic tool. Commercially available antibody–testing is limited to several autoantibodies. Others need to be sent to certain research laboratories. Additionally, several papers caution about frequently occurring false positive or false negative results and advise testing using several different detection techniques, such as brain tissue immunohistochemistry and live–cell based assays. It is crucial to think about the diagnosis of the patients very carefully not depending on only the results of the autoantibody–test, but rather observing detailed clinical features for proper treatments.

著者

関 守信

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.40, no.3, pp.352-354, 2023 (Released:2023-08-21)

参考文献数

11

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Since Prof. David Marsden pointed out the challenges (i.e. motor complications) associated with long–term L–dopa therapy in 1977, various efforts and innovations have been made to overcome motor complications. This article focuses on the role of novel anti–parkinsonian drugs in advanced Parkinson Disease (PD), including those approved and under development overseas. It is important to achieve continuous dopaminergic stimulation (CDS) in order to improve motor complications. Treatment strategies to achieve CDS with novel drugs include optimization of L–dopa delivery, optimization of L–dopa pharmacokinetics, parenteral administration of short–acting dopamine agonists, and oral administration of long–acting dopamine agonists. Amantadine extended release has been developed for levodopa–induced dyskinesia. L–dopa inhalation powder and apomorphine sublingual film are approved and marketed overseas as rescue drug for off–period.

著者

小野 賢二郎

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.40, no.3, pp.233-236, 2023 (Released:2023-08-21)

参考文献数

19

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According to estimates by the Ministry of Health, Labor and Welfare, the number of dementia patients in 2012 was 4.62 million, and the number of mild cognitive impairment patients was about 4 million. For the diagnosis of dementia, treatable dementia is first ruled out, and then common dementia such as Alzheimer disease (AD), vascular dementia (VaD), and dementia with Lewy bodies (DLB) are differentiated. The typical symptoms of AD include time disorientation and delayed recall disturbance. Cerebral blood flow single photon emission computed tomography (CBF–SPECT) shows poor blood flow in the posterior cingulate gyrus and/or precuneus in AD patients. In VaD, cognitive impairment is milder than in AD, and there are clinical courses such as stepwise exacerbation of symptoms, and various cerebrovascular lesions are observed on brain MRI. The patients with DLB have clinical symptoms such as visual hallucinations and Parkinsonian symptoms. CBF–SPECT and MIBG myocardial scintigraphy show the decreases of occipital lobe blood flow and cardiac uptake, respectively.At the present, acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine are currently available for the treatment of AD. Although these drugs are limited to symptomatic therapy in AD patients, recently, approaches aimed at disease–modifying therapy (DMT), especially the approaches focused on amyloid β–protein (Aβ) have been developed remarkably. Anti–Aβ antibody therapy is central to the current development of DMT for AD. Clinical trials of anti–Aβ antibodies have repeatedly reported poor results, but clinical trials of anti–Aβ antibodies that target Aβ aggregates, such as aducanumab and lecanemab, have reported significant effects on the primary endpoint in phase 3 trials.

著者

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.37, no.5, pp.709-711, 2020 (Released:2021-07-21)

参考文献数

4

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It remains uncertain how brain circulation has effects on cognitive function in aging. Cerebral blood flow (CBF) decreases with advancing ages and in cognitive decline, apparently in vascular dementia and modestly in Alzheimer disease. Brain is an organ which requires enormous amount of CBF and metabolism compared to the other organs, and therefore, cerebral circulation is protected through autoregulation and subsequently, enhancement of oxygen extraction by neuronal structures even when CBF is decreased due to stenosis or obstruction of cerebral vessels.The damages in the grey matter is relatively mild, but the white matter becomes rarefied with gliosis and nerve fiber loss, if the decrease of CBF remains for a long duration at the level ranging from 50 to 70% of the baseline. In the long run, the patients may exhibit brain atrophy and cognitive decline. The mechanism of dementia in cerebrovascular disease, including small vessel dementia, is relatively straightforward, whereas in Alzheimer disease, it remains unclear how chronic cerebral hypoperfusion may lead to cognitive dysfunction and dementia. Apparently, chronic cerebral hypoperfusion induces neuro–inflammation, disintegration of blood–brain barrier (BBB) and altered excretion of amyloid beta via dysfunction of periarterial drainage pathway and glymphatic system. This review overviews the relationship between cerebral circulation disturbance and cognitive decline with advancing ages.

著者

竹島 多賀夫

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.39, no.4, pp.564-568, 2022 (Released:2022-12-27)

参考文献数

18

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Migraine is a highly disabling prevalent neurological disease. Cortical spreading depression/depolarization, central sensitization, and neurogenic inflammation in trigemino–vasular system involve the pathophysiology of migraine. Serotonin, dopamine, and calcitonin gene related peptides relate closely these phenomenon.The relationship between headache disorders and sleep disorders can categorize 1) headaches cause sleep disorders, 2) sleep disorders (disturbances) cause or worse headaches, 3) Somewhat common factor(s) cause both headache and sleep disorders.In this lecture, I summarized possible relation of migraine and sleep disorders including sleep apnea, somnambulism, restless legs syndrome, narcolepsy.21st century headache involves new territory and special concern to sleep hygiene are essentially important.

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.6, pp.617, 2016 (Released:2017-04-30)

著者

堀越 一孝 伊藤 恒 福武 滋 阿部 誠也 角田 賢史 渡邊 宏樹 亀井 徹正

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.5, pp.601-605, 2019 (Released:2020-06-02)

参考文献数

7

被引用文献数

1

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Hybrid Assistive Limb医療用下肢タイプ(HAL®)による歩行運動療法を継続した筋萎縮性側索硬化症(amyotrophic lateral sclerosis:ALS)の1例を報告する.症例は61歳女性.4点杖による介助歩行が可能で,座位・立位姿勢にて頸部と体幹の前屈を認めていた.Edaravoneの経静脈的投与と並行して,歩行能力の維持を目的として1クールあたり20分/日×9日を基本とするHAL®による歩行運動療法を開始した.1クール目の終了時には歩行機能が改善し,14~31日のインターバルをおきながら歩行運動療法を継続した.経過を通じて歩行機能は緩徐に低下したが,歩行運動療法の各クール終了時には歩行機能の改善が認められた.また,座位での頸部・体幹の前屈が一過性に改善した.HAL®による歩行運動療法を継続することにより,短期的ではあるが,歩行機能と体幹機能の改善が期待できることが示唆された.

著者

川上 治 古池 保雄 安藤 哲朗 杉浦 真 加藤 博子 横井 克典 都築 雨桂

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.51-55, 2017 (Released:2017-05-31)

参考文献数

15

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目的:脳梗塞後はじめて発作を発症した場合,てんかんと診断できるか検討するため,有事率とそのリスク,非誘発性発作の再発率等について多数例を後ろ向きに調査した.方法:当院に入院した脳梗塞急性期(transient ischemic attack;TIAを除く)患者2071名を対象に,けいれん発作発症例を抽出した.年齢,性,皮質病変,Oxford分類,MRIでの深部白質病変等を評価項目とした.結果:脳梗塞発症後,急性症候性発作(acute symptomatic seizure;ASS)は43例で過半数は発症当日であった.非誘発性発作(unprovoked seizure;US)は,100~300日でピークとなるがその後も増加を続け,5年間で73例であった.ASSのリスクは,皮質病変・total anterior circulation infarction;TACI(Oxford分類),USのリスクは,皮質病変・TACI・partial anterior circulation infarction;PACI(Oxford分類)・deep and subcortical white matter hyperintensity;DSWMH(グレード3・4)・75歳未満(多重ロジスティック回帰法)であった.再発性USは,US群74%,ASS群9%と有意にUS群で高かった.初発より抗てんかん薬(antiepileptic drugs;AEDs)を投与すると有意に再発率が減少した.非誘発性発作の重積発作発生率は,AEDs投与群19.6%,非投与群34.3%と有意にAEDs投与群が少なかった.結論:脳梗塞慢性期に初発発作を発症した場合は,てんかんと診断できる.AEDsは,US再発およびてんかん重積状態の予防に有効であり初発USより投与開始を検討する必要がある.

著者

下畑 享良

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.40, no.1, pp.3-6, 2023 (Released:2023-04-20)

参考文献数

14

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This editorial describes new MDS criteria for multiple system atrophy (MSA). The criteria aim to improve the accuracy of the diagnosis of MSA and to increase diagnostic accuracy in the early stages of the disease leading to increased patient enrollment in clinical trials. The criteria provide detailed definitions of diagnostic findings in a lexicon, which should be reviewed during the interview and diagnosis. The criteria define four levels of diagnostic certainty. The newly created “possible prodromal MSA” is a research category with low specificity, but it is expected to be used to establish future diagnostic biomarkers to catch patients in the earliest stages of the disease.

著者

原 誠

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.4, pp.543, 2018 (Released:2019-04-22)

著者

北原 匠 加藤 泰介 小野寺 理

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.39, no.4, pp.439-443, 2022 (Released:2022-12-27)

参考文献数

39

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Cerebral small vessel disease is a common disease that affects small vessels in the brain and is associated with stroke, cognitive impairment, and motor dysfunction. The blood–brain barrier and endothelial cell function have been the focus of attention as the etiology of the disease. Recently, the mechanisms of waste removal and neural activity–dependent redistribution of blood flow in the brain have been clarified, and the functions of pericytes, smooth muscle cells, and arterioles have been studied. However, the pathogenesis of the disease is still unknown. Since the prevalence of cerebral small vessel disease increases with age, aging is the most important risk factor. Hypertension is also one of the most important risk factor for cerebral small vessel disease, but even in modern times when antihypertensive therapy is widely available, the onset and progression of symptoms have not been adequately controlled. Recent genome–wide studies have revealed that many genes related to extracellular matrix are included in the risk genes for sporadic cerebral small vessel disease, and their involvement in the pathogenesis is suspected. In addition, HTRA1, the causative gene of hereditary cerebral small vessel disease, is included in the risk genes. This suggests that extracellular matrix changes may be a common pathogenesis of sporadic and hereditary cerebral small vessel disease.

著者

桑名 正隆

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.39, no.3, pp.218-223, 2022 (Released:2022-11-22)

参考文献数

35

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Idiopathic inflammatory myopathies (IIMs) are a group of disorders complicated by inflammation and resultant damage of skeletal muscles without known causes. Major advances have been recently made in the field of IIMs, including new classification criteria to better identify the patients with IIMs, and discovery of detailed muscle pathologic features and myositis–specific and myositis–associated autoantibodies that facilitates subgrouping of patients into more specific clinical phenotypes. IIMs are now classified into four major subgroups, i.e., dermatomyositis (DM), anti–synthetase syndrome (ASSD), immune–mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Patients with concomitant features of other connective tissue diseases are considered overlap syndrome. Almost all patients who used to be diagnosed as having ‘polymyositis’ are now re–classified as IBM, IMNM, or ASSD. IIMs are originally characterized by the presence of myositis, but it has been recently recognized that patients with typical DM rashes or myositis–specific autoantibodies plus interstitial lung disease without apparent skeletal muscle involvement are also included in this spectrum. Recent studies evaluating immunophenotypes of individual IIM subgroups have shown distinct pathophysiologies : type I interferonopathy and activation of the complement system in DM, type II interferon activation in ASSD, autoantibody–mediated complement activation in IMNM, and a primary role of CD8+ T cells in IBM. This information is useful in developing unique therapeutic approaches to individual IIM subgroups. Although corticosteroids are still the first–line therapeutic agents, their long–term use is known to increase serious side effects that affect patients' quality of life and survival. Attempts to minimize the accumulated dosage and duration of corticosteroids has been made in patients with systemic lupus erythematosus, and are now applied to patients with IIMs. For this purpose, initial combination of immunosuppressive drugs and molecular–targeting drugs is being actively introduced in the field of IIMs. Over the next few years, management of IIMs will undergo major advances and will be able to provide better medical care to the patients.

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.40, no.2, pp.86-91, 2023 (Released:2023-05-25)

参考文献数

30

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Interventions before the onset of cerebrovascular disease in terms of preventive medicine, it is classified into 2 stages. As for zero–level prevention, it is a lifestyle intervention for the entire population. So–called primary prevention is an approach to a group of patients who already have vascular risk factors.Zero–level prevention : To reduce the occurrence of risk factors for cerebrovascular disease, the goal is to educate the public widely on the impact of risk factors on the development of stroke and cardiovascular disease, and to manage lifestyle habits appropriately. These include salt reduction, smoking cessation, alcohol conservation, and improved nutrition and diet, including increased physical activity, and are tailored to each stage of life in all generations.Primary prevention : Appropriate management of major risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and atrial fibrillation, to prevent their development. The goal of blood pressure control is set at <130/80 mmHg and a combination of calcium channel blockers, diuretics, angiotensin–converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), are recommended. In diabetic patients, not only proper management of blood glucose, but also strict control of cardiovascular risk factors such as blood pressure and dyslipidemia is important for stroke prevention. In patients with dyslipidemia, LDL–cholesterol should be controlled to <120 mg/dL. On top of diet, HMG–CoA enzyme inhibitors (statins), ezetimibe, proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are used. For patients with non–valvular atrial fibrillaiton, primary prevention of cardiogenic cerebral embolism is achieved with anticoagulants starting at a CHADS2 score of 1. Prefer DOAC over warfarin. Left atrial appendage closure devices are now also considered in atrial fibrillation patients at high risk of bleeding.

著者

清水 俊夫

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.39, no.1, pp.22-26, 2022 (Released:2022-06-15)

参考文献数

55

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Weight loss is frequently observed in early–stage amyotrophic lateral sclerosis (ALS) and is considered an independent predictor of survival. Weight loss observed in ALS is associated with multifactorial etiology, including muscle wasting and dysphagia ; however, recent studies have implicated disease–specific hypermetabolism in weight loss and disease progression in ALS. The pathophysiology of hypermetabolism as a contributor to weight loss in ALS remains unclear ; however, hypothalamic involvement is considered an early extra–motor manifestation of ALS. TDP–43 protein aggregates detected in the hypothalamic subnuclei may be associated with weight loss or abnormalities of eating behavior in patients with ALS. Weight loss from diagnosis up to tracheostomy also predicts functional prognosis during the long–term period with ventilator. In fact, patients with ALS who survive with prolonged mechanical ventilatory support often develop significant brain and brainstem atrophy, including atrophy of the limbic motor system and the hypothalamus. Nutritional intervention to maintain body weight may be a useful disease–modifying therapeutic approach, and recent studies have reported that slowing of weight reduction rate after diagnosis may be associated with better survival and that a high–calorie diet improves survival in patients with rapidly progressive disease. Nutritional education regarding a high–calorie diet, weight control, and early gastric tube placement are important after diagnosis. Researchers from the USA, Europe, and Japan have established formulas to estimate the recommended daily energy intake. Although a lipid shift in energy metabolism might occur in the brain and muscles in patients with ALS, the effectiveness of high–fat diets requires further investigation.

著者

宮﨑 雄生

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.39, no.6, pp.S133, 2022 (Released:2022-10-20)

著者

石川 英洋 新堂 晃大 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.39, no.3, pp.346-349, 2022 (Released:2022-11-22)

参考文献数

14

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Kelch–like protein 11 (KLHL11)–associated paraneoplastic syndrome (PNS) has been newly categorized as PNS. The corresponding syndromes are cerebellar and/or brainstem involvement, and in the fewer cases, limbic encephalitis. Hearing loss or tinnitus often precedes other symptoms. Findings of cerebrospinal fluid show inflammatory (protein 50mg/dL or greater and leukocyte counts exceeding 5 cells/µL) with oligoclonal bands in over 80% cases. The most common associated tumor is testicular germ cell tumor, especially seminoma. The primary testicular tumor is often spontaneously regressed with or without metastasis in lymph nodes, called a burned–out testicular tumor. Ultrasonography of testis is useful for such cases because it can detect the suggestive findings of burned–out tumors such as fibrosis and microlithiasis as hypoechoic area. The principles for management are treatment of underlying cancer and immunotherapy. KLHL11–PNS may have a more refractory course than PNS associated with antibodies against neural cell surface antigens since KLHL11 antibodies are targeting intracellular autoantigens and cause cytotoxic T–cell–mediated pathogenesis. A recent paper published by Autoimmune Encephalitis Alliance Clinicians Network recommends that tumor treatment and intravenous methylprednisolone followed by short oral taper should be performed as first–line therapy. If there is no improvement cyclophosphamide can be the next option. Then experimental therapy like IL–6 inhibitor or bortezomib can be considered in non–responded cases.