著者
髙畑 克徳 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.33, no.1, pp.9-18, 2016 (Released:2016-05-20)
参考文献数
19

Autoimmune encephalopathies are clinically and immunologically heterogeneous disorders. Over time, many different types of autoimmune encephalopathy have been discovered. In such clinical situations, we often recognize that patients with autoimmune encephalopathy are often misdiagnosed as exhibiting functional psychogenic movement, conversion, or somatoform disorders. We clinically analyzed 63 patients (14 males and 49 females; age range, 15–79 years) diagnosed with autoimmune encephalopathy in our hospital from 2013 to 2015. Throughout this period we diagnosed almost no conversion disorders in our department. These patients were diagnosed using the diagnostic criteria for each disease, following clinical features showing neurological symptoms of brain origin, responsiveness to immunosuppressive therapy, the existence of known pathological antibodies, and/or history of human papilloma virus (HPV) vaccination. Fourty–two patients showed motor disturbance (weakness, paresis of extremities, or slower pinching) and 35/42 (83.3%) patients showed give–way weakness, indicating disruption of continuous muscle contraction. Fourty–four patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or fast neurologic pain. Surprisingly, most pain was distributed in manner that was not explainable anatomically, while some patients also showed patchy, stocking–glove, or localized pain. Seventeen patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. In most patients, such motor, sensory, or involuntary movements were markedly improved with immunosuppressive therapies such as prednisolone, azathioprine, or immune adsorption therapy. We observed memory loss, PNES (psychogenic non–epileptic seizure), dissociative amnesia, hyperventilation, opsoclonus, epilepsy, or autonomic symptoms amongst our patients. Although give–way weakness, anatomically unexplainable pain/abnormal sensation, and strange involuntary movements were thought to be psychogenic, the presence of one of these three symptoms was indicative of autoimmune encephalopathy. As autoimmune encephalitis exhibits diffuse involvement with the whole brain, these symptoms were entirely understandable. Except for the presence of organic disease, most patients were classified into somatoform disorders (DSM–IV, ICD–10) or functional movement disorders. Without first excluding autoimmune encephalopathy, we propose that physicians should not diagnose somatoform disorders. Since autoimmune encephalopathy patients often possess so–called psychogenic signs, it is possible that such signs might be generated by autoimmune encephalopathy instead of somatoform disorders. In conclusion, we propose that give–way weakness and anatomically unexplainable pain/abnormal sensation are key symptoms of autoimmune encephalopathy. We hope that many patients with autoimmune encephalopathy will now be identifiable using our new neurological examination and that each patient can be given an exact diagnosis and therefore be administered with the appropriate treatments.
著者
渡邊 恭良 倉恒 弘彦
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.33, no.1, pp.40-45, 2016 (Released:2016-05-20)
参考文献数
16

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that inflammation in the CNS is involved in the pathophysiology of CFS/ME, there were no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia and/or astrocytes is related to neuroinflammation. Our recent PET study successfully demonstrated that neuroinflammation (activation of microglia and astrocytes) is present in widespread brain regions in patients with CFS/ME, and is associated with the severity of neuropsychological symptoms. Evaluation of neuroinflammation in patients with CFS/ME may be essential for understanding the core pathophysiology, as well as for developing the objective diagnostic criteria and effective medical treatments for CFS/ME. We here describe related pathophysiological findings and topics, and mention the diagnostic and therapeutic attempts through these findings in Japan.
著者
池田 修一
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.1, pp.32-39, 2016 (Released:2016-05-20)
参考文献数
25

A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus (HPV) vaccination. The average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in the girls with limb symptoms exhibited a slight decrease in the fingers and a moderate decrease in the toes. Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of the affected girls were compatible with the diagnostic criteria for complex regional pain syndrome (CRPS). The Schellong test identified a significant number of patients with orthostatic hypotension and a few patients with postural orthostatic tachycardia syndrome. Electron–microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. Additionally delayed manifestation of cognitive dysfunction in the post–vaccinated girls has been paid much attention: memory loss, difficulty in reading textbooks and/or calculation.
著者
犬塚 貴 木村 暁夫 林 祐一
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.2, pp.94-98, 2016 (Released:2016-08-10)
参考文献数
20

Several autoantibodies are associated with autoimmune encephalitis. Some of these antibodies are directed against intracellular neuronal antigens such as Hu and Ma2, which are strongly associated with paraneoplatic syndrome. In the past 10 years, various antibodies were identified that recognize neuronal cell–surface or synaptic proteins in patients associated with or without malignancy. Some of these antibodies are able to directly access receptors of neurotransmitters or channels and are responsible for causing neurological syndromes. Autoimmune encephalopathy with these antibodies generally responds to immunotherapies, such as steroids, plasmapheresis, and intravenous immunoglobulin as well as immunosuppressant and anti–cancer treatments in cases of paraneoplastic syndrome.Patients with N–methyl–D–aspartate (NMDA) receptor antibodies, which are the most common in autoimmune encephalopathy, often cause psychiatric manifestation, memory impairment, seizures, dyskinesia, catatonia, autonomic instability and respiratory failures. Although 86% of patients become worse at the stage of mRS5, almost 80% of all patients recover to the stage of less than mRS2 with immunomodulatory therapy and careful management for their general condition. Detection of those antibodies in both serum and CSF using cell–based assays is important for definite diagnosis. Availability of screening systems of antibodies and covering health insurance for immunomodulatory therapy for autoimmune encephalitis are highly expected.
著者
高橋 幸利 木水 友一 小池 敬義 堀野 朝子
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.33, no.1, pp.19-26, 2016 (Released:2016-05-20)
参考文献数
27

A. Non–herpetic acute limbic encephalitis & anti–NMDAR encephalitis Non–herpetic acute limbic encephalitis is diagnosed with the characteristic onset symptom of limbic system and absence of herpes simplexes virus in CSF. Anti–NMDAR encephalitis is diagnosed with presence of antibodies to complex of NMDA–type GluR subunits by cell–based assay. Non–herpetic acute limbic encephalitis & anti–NMDAR encephalitis are causally related with antibodies to NMDA–type GluR, which internalize complex of NMDA–type GluR subunits on neural cell surface. Internalization may lead to protection from apoptosis by excitotoxicity related with increased glutamate and cytokines, and less phosphorylation of Akt in these encephalitides. Passive transfer of rabbit antibodies to n–terminal of human GluN2B into hippocampi of mice caused probable excited behavior and impairment of memory in behavioral analysis, and decreased expression of pam gene in microarray analyses and quantitative analyses of gene expression. In non–herpetic acute limbic encephalitis, factors including granzyme B, glutamate, etc., other than antibodies are causally related with neuronal cell death.B. Encephalitis mediated by antibodies to voltage–gated potassium channel (VGKC) In encephalitides mediated by antibodies to VGKC, patients with antibodies to leucine–rich glioma–inactivated 1 (LGI1) show characteristics of limbic encephalitis, and patients with antibodies to contactin–associate protein (Caspr) 2 show Morvan's syndrome with thymoma.C. Acute disseminated encephalomyelitis (ADEM) ADEM is the most common immune–mediated encephalitis, and its immune–mediated pathophysiology was not revealed. Recently, antibodies to myelin–oligodendrocyte glycoprotein were found in a few pediatric patients.
著者
堺 竜介 甲田 亨 馬場 孝輔 奥野 龍禎 中辻 裕司 望月 秀樹
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.47-50, 2017 (Released:2017-05-31)
参考文献数
9

症例は69歳の男性である.右耳介の発赤腫脹の後,活動性の低下,パーキンソニズムを呈し,頭部MRIにて両側対称性に大脳基底核に高信号を認めた.その後,精神症状が亜急性に進行し,髄液中の細胞と蛋白の増加があり,造影効果も認め,自己免疫性脳炎と考えてステロイドパルス療法を実施した.改善を認め転院となったが,その後辺縁系を含め広範囲に病変を呈し当院へ再入院となった.ステロイドパルス療法を実施し症状,頭部MRI画像での改善が再度得られた.後に抗N–methyl–D–aspartate(NMDA)受容体抗体が陽性と判明,経過を通じて悪性腫瘍の合併も明らかではなく非典型的な経過ではあるが,抗NMDA受容体脳炎と考えられた.パーキンソニズムで発症し,病初期の画像は基底核病変のみで,緩徐に進行する脳炎でも抗NMDA受容体脳炎を考慮し,精査する必要があると考えられる.
著者
赤松 恵 山下 雄也 郭 伸
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.2, pp.86-94, 2017 (Released:2017-07-25)
参考文献数
36

Both TAR DNA binding protein of 43kDa (TDP–43) pathology and failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2, a subunit of the α–amino–3–hydroxy–5–methyl–4–isoxazole propionic acid (AMPA) receptor, are the characteristic etiology–linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS), the most common adult–onset fatal motor neuron disease. Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes RNA editing at the Q/R site of GluA2, and conditional ADAR2 knockout mice (ADAR2flox/flox/VAChT–Cre.Fast ; AR2 mice) exhibit a progressive ALS phenotype with TDP–43 pathology–like TDP–43 mislocalization in the ADAR2–lacking motor neurons. Because Ca2+–permeable AMPA receptor–mediated mechanism underlies death of motor neurons in the AR2 mice, amelioration of exaggerated Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here we showed that oral perampanel, a selective non–competitive AMPA receptor antagonist, significantly prevented progression of ALS phenotype and death of motor neurons with effective normalization of TDP–43 pathology in the AR2 mice. Given that perampanel has already been approved as an anti–epileptic drug, perampanel would be a potential candidate ALS drug.

3 0 0 0 OA 編集後記

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.4, pp.616-616, 2016 (Released:2017-02-28)
著者
荒木 信夫
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.33, no.1, pp.5-6, 2016

The Japanese Society of Neurological Therapeutics is pleased to announce the launch of an electronic version of the Societys journal. Beginning in 2016, the Societys journal will be open access and all manuscripts will be accessible in both PDF and HTML (XML) format on J–STAGE (Japan Science and Technology Information Aggregator, Electronic). Each manuscript will have a unique digital object identifier (doi) that provides a permanent link to the manuscript and facilitates citation by researchers anywhere in the world. Members of the Japanese Society of Neurological Therapeutics will receive regular emails that include the table of contents of new issues as well as other important information about the journal.

1 1 0 0 OA 重症筋無力症

著者
本村 政勝
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.3, pp.318-322, 2016 (Released:2016-11-10)
参考文献数
10

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by impaired neuromuscular transmission due to circulating pathogenic autoantibodies. MG patients produce pathogenic autoantibodies against the acetylcholine receptors (AChR), muscle–specific receptor tyrosine kinase (MuSK), and low–density lipoprotein receptor–related protein 4 (Lrp4) which are localized on the postsynaptic membrane of the neuromuscular junction. This lecture provides the overview of MG in Japan including classification, epidemiology, autoantibodies, clinical manifestation, diagnosis, treatment, and prognosis, especially focusing on the new standard treatment approach according to novel MG diagnostic criteria suggested by the MG clinical guidelines for 2014. Treatments for MG are based on immunotherapy by steroids and immunosuppressants. In Japan, treatments include cholinesterase inhibitors, thymectomy, steroids, immunosuppressants, plasma exchange, and intravenous immunoglobulin therapy. However, even when utilizing all of these treatments, the proportion of MG patients achieving complete stable remission is less than 10%. The new treatment approach suggests the combination therapy from early disease stage, to reduce the risk of crisis and disease progression. The current goal of MG treatment is firstly to treat MG patients to achieve pharmacological remission as rapidly as possible using the above therapies at onset. The therapeutic protocol according to onset age, disease type, and pathogenic autoantibodies conducted in Nagasaki University Hospital is also discussed.
著者
平田 雅之
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.33, no.3, pp.399-404, 2016 (Released:2016-11-10)
参考文献数
19

Research and development of brain-machine interfaces (BMIs) are now ongoing to support severely disabled people due to intractable neurological disease, spinal cord injury and stroke etc. Implantable brain-machine interfaces using intracranial electrodes require surgical intervention. However, it may achieve higher performance. Here I describe the trends of domestic and international BMI research for clinical application.In USA, clinical research of BMIs using micro–needle electrode array are ongoing in University of Pittsburgh and in Brown University. They reported that three dimensional real time control of a robotic arm and writing using a mouse cursor were successfully performed by severely disabled people. We demonstrated that, real time control of a robotic arm was successfully performed by patients with intractable epilepsy or intractable pain whom intracranial electrodes were temporarily implanted. And most recently we demonstrated that a severely disabled patient with ALS successfully controlled a robotic arm and writing.A fully implantable device is another key to clinical application for implantable BMIs. Development of 40 to 100 channel implantable devices are ongoing in USA, France and Germany. However clinical application of these implantable devices has not been reported yet. We developed a 128–ch electrocorticographic fully implantable device using a contour fitting 3D cortical electrodes and completed chronic implantation in monkey for 6 months. Translational research with companies is indispensable for clinical application. We have to establish a business model and perform strategic pharmaceutical affairs based on it.From technological point of view, implantable BMIs will be clinically applied in the next 5 to 10 years. Now it's time to think well about its application.
著者
菊池 友和 山口 智 鈴木 真理 荒木 信夫
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.33, no.3, pp.480-483, 2016 (Released:2016-11-10)
参考文献数
12

1ヶ月以上薬物療法を行い効果の得られなかった反復発作性緊張型頭痛(frequent episodic tension–type headache:FTTH)と慢性TTH(chronic TTH:CTTH)に分類し,鍼治療を行い,Visual Analogue Scale(VAS)による自覚症状の評価が50%以上改善したのを有効として,両群の治療回数・期間について検討した.対象は,TTH221例.FTTH82例(男28,女54,平均年齢52.7歳)とCTTH139例(男44,女95,平均年齢50.4歳)である.FTTHの有効率80.1%,CTTHの有効率59.9%であり,FTTH群の方が有意に高値であった(p<0.01).回数・期間はFTTH 2.8回14.9日,CTTH8.9回35.9日であり,FTTHの方が少ない回数で短期間に改善した(p<0.01).FTTHは,鍼治療を3回または2週間継続し,さらにCTTHは9回または5週間継続し効果判定する必要性が示された.