臨床神経学
Online ISSN : 1882-0654
Print ISSN : 0009-918X
ISSN-L : 0009-918X
51 巻 , 11 号
選択された号の論文の154件中1~50を表示しています
第52回日本神経学会学術大会(2011年)
会長講演
  • 祖父江 元
    2011 年 51 巻 11 号 p. 821-824
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Although recent advancements in molecular biology have provided increasing insights into the pathophysiology of neurodegenerative diseases, there is almost no disease-modifying therapy for which the efficacy has been verified in clinical trials. Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by the expansion of a trinucleotide CAG repeat in the androgen receptor (AR) gene. SBMA exclusively affects males, whereas does not manifest in the females homozygous for the AR mutation. The ligand-dependent nuclear accumulation of pathogenic AR protein is central to the pathogenesis, although additional steps such as inter- and intra-molecular interaction are also required for toxicity. Leuprorelin, a luteinizing hormone-releasing hormone (LHRH) analogue that suppresses testosterone production from testis, inhibits toxic accumulation of pathogenic AR, thereby mitigating histopathological and behavioral impairments in a mouse model of SBMA. Although a randomized placebo-controlled multi-centric clinical trial showed no definite effect of the drug on motor functions, there was the improvement of swallowing function in a subgroup of patients whose disease duration was less than 10 years. These results indicate a need to elucidate the entire disease mechanism, clarify the natural history, initiate therapeutic intervention at an early stage, and develop sensitive outcome measures to evaluate drug effect.
特別講演1
特別講演2
教育講演1
教育講演2
  • 飯島 祥彦
    2011 年 51 巻 11 号 p. 830-833
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Clinical research is guided by ethical principles promulgated in several statements, principally the Nuremberg Code, the Helsinki Declaration of the World Medical Association etc. In Japan, clinical research of medical products, principally trial of new pharmaceutical products is regulated by GCP (good clinical practice). Other types of clinical research are regulated by some ethical guidelines for clinical researches. The result is a regulatory position that is a complex combination of legislation and ethical guidelines. In the Ethical Guideline for Clinical Studies revised in 2008, clinical research is classified into intervention research and observational research. When researchers plan clinical research, they must determine the type of clinical research and appropriate ethical guideline for the type of clinical research.
    Advances in health informatics and genetic research have produced a new and very rich body of raw material for clinical research in the form of gene banks and genome-wide association study etc. The use of human tissue and medical information in the course of clinical research raises issues under the ethical regulations for research with human subjects.
教育講演3
  • 犬塚 貴, 林 祐一, 木村 暁夫
    2011 年 51 巻 11 号 p. 834-837
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Paraneoplastic neurological syndrome (PNS) is a rare disorder caused by the remote effects of cancer and is considered as immune-responses to the molecules on cancer which cross-react with self-antigens in the nervous system. Since the 1980s, several specific anti onconeural antibodies have been reported, which are useful diagnostic markers of PNS and occult cancer. Only a few onconeural antibodies have been identified as primary effectors of neurological damage. Recently sophisticated methods for the detection of new or low titer antibodies have been developed. Several new auto-antibodies against receptors or ion channels on the surface of neuronal membrane, such as NMDA receptors, AMPA receptors, GABAB receptors and VGKC complexes, have been reported in the patients with encephalopathy including limbic encephalitis. These diseases can be associated with tumor, but they are more often non-paraneoplastic. These antibodies are generally good biomarkers for effective immunomodulatory treatment for immune-mediated encephalitis with not only consciousness disturbance but also dementia, seizures and psychiatric symptoms which sometimes mimic schizophrenia. Further studies are required to clarify the exact mechanisms underlying neuronal damage in immune-mediated neurological diseases including PNS, which may lead to the development of more rational therapies and greater understanding of immunology in the nervous system.
教育講演4 多系統萎縮症の変性のはじまりは神経細胞からかグリア細胞からか
教育講演5
  • 中野 今治
    2011 年 51 巻 11 号 p. 844-847
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    FTLD is a neuroanatomical disease concept defined only by the presence of degeneration of the frontal and temporal lobes regardless of the underlying histopathological features, and therefore inevitably includes heterogeneous diseases that affect those cerebral regions. The ambiguous idea of Pick disease, the prototype of FTLD, constantly caused great nosological confusion as to FTLD. Progress in molecular neuropathology aimed at clarification of the protein constituents of the inclusion bodies seen in conditions causing FTLD, however, has resolved this problem by providing FTLD with a new concise nomenclature and classification based on the inclusion body proteins. The substances in inclusions in FTLD with ubiquitin-only inclusions (FTLD-U) have been discovered one after another; TDP-43 was the first, being found in inclusions in ALS and ALS with dementia (ALSD) too, and soon FUS/TLS was identified in some TDP-43-negative FTLD-U groups. Thus, FTLD has been divided into three main subgroups; 1) FTLD-tau, which includes Pick disease, PSP, CBD, etc., 2) FTLD-TDP, which is further divided to types A-D, ALSD belonging to type B, and 3) FTLD-FUS, which includes aFTLD-U, NIFID, and BIBD. Further deciphering of yet-unidentified proteins of some FTLD-U subsets will add more subclasses.
教育講演6
教育講演7
  • 武藤 多津郎
    2011 年 51 巻 11 号 p. 849-852
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Many researchers now recognize the importance of glycobiological research achievements. Glycoside-containing substances such as proteins (glycoproteins) and lipids (glycosphingolipids) have been involved in many important and essential events for normal life. The production of glycoside residues of the proteins is only partially regulated by the genes. In this talk, I will make a brief description of what glycobiology can influence the future of neurological research arena and how glycoproteins and glycolipids affect the normal biology of the neurons. Furthermore, I will introduce you some evidences that many neurological disorders such as Alzheimer's disease and immune-mediated encephalitis have special relationships with glycobiological abnormalities. I also explain the structures and functions of lipid rafts, caveolae, and glycosynapse and their roles in the intracellular signal transduction and cell motility.
教育講演8
  • 若林 俊彦
    2011 年 51 巻 11 号 p. 853-856
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    悪性脳腫瘍はきわめて予後不良の疾患であり,とくに,膠芽腫は5年生存率10%にもいたらぬ難治性疾患である.そのため,予後改善を目指して,各種新規治療法が試みられている.その中でも,多重膜カチオニックリポソームに包埋されたインターフェロンβ遺伝子製剤を使用した本邦初の脳腫瘍の遺伝子治療の臨床応用は,長期間の臨床的評価でもきわめて安全性が高く,その臨床効果も一定の評価がえられた.現在,次世代型の治療開発として,GMPレベルでの生産が可能であるLipofection法によるsiRNAをもちいた核酸医薬の開発を目指している.脳内の的確な位置に製剤を投与するための脳神経外科ロボット"Neuro Mate"のアジア初の手術室への設置により,薬物の脳内拡散を最大限にするConvection enhanced delivery法の応用で,薬剤効果を最大限に活かせる手法もその研究が進んでいる.これらナノパーティクルを脳内に的確に投与する,いわゆる,ナノサージェリーは,医工連携による技術革新に裏打ちされ,脳神経外科領域の診断・治療の飛躍的な進歩が予見される.
教育講演9
  • 橋本 衛
    2011 年 51 巻 11 号 p. 857-860
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Behavioral and psychological symptoms of dementia (BPSD) is the term defined as symptoms of disturbed perception, thought content, mood or behavior that frequently occur in patients with dementia. As BPSD can cause remarkable distress for both the patient and the caregiver, clinicians are required to treat the symptoms effectively.
    Before undertaking an intervention to BPSD, patients should be assessed in a detailed clinical interview to establish symptoms causing distress to the patient and/or caregiver. Initial intervention should focus on nonpharmacologic measures. However, pharmacologic intervention is necessary in many cases. There are many classes of medications to choose from for treating BPSD, but the evidence behind treatment is varied and confusing. Clinicians should discuss the potential risks and benefits of treatment with patients, and must ensure a balance between side effects and tolerability compared with clinical benefit and QOL.
    To provide medical care to the patients with dementia represents the comprehensive management of them, including differential diagnosis, treatment of BPSD and education of caregivers. Almost all of the patients with dementia develop BPSD during the course of the disease. As long as dementia is a neurological disorder, both neurologists and psychiatrists should work cooperatively in the treatment of dementia.
教育講演10
教育講演11
教育講演12
  • 渡辺 宏久, 吉田 眞理, 長縄 慎二, 祖父江 元
    2011 年 51 巻 11 号 p. 863-864
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Diffusion tensor imaging and voxel based morphometry are efficient in the diagnosis of neurodegenerative disorders, however, these technologies are available at a limited number of facilities. Thus, conventional MRI remains important in the diagnosis of neurodegenerative disorders.
    Dorsolateral putaminal hyperintensity (DPH) and hot cross bun sign discriminate Parkinson's disease from multiple system atrophy (MSA). However, differences in magnetic field strength and sequence affect the sensitivity of DPH, and mild DPH may be observed in normal elderly subjects.
    Patients with progressive supranuclear palsy (PSP) presenting Richardson's syndrome show midbrain tegmentum atrophy, but Parkinsonian PSP (PSP-P) and pure akinesia with gait freezing, which are other phenotypes of PSP, may not show especially during early course of illness. In patients with corticobasal degeneration (CBD), asymmetrical cerebral atrophy corresponding with corticobasal syndrome (CBS) may be a characteristic finding. However, at autopsy, CBS patients presenting asymmetrical cerebral atrophy have CBD as the underlying pathology in approximately 50% of PSP patients.
    The sensitivity and specificity of MRI for the diagnosis of MSA, PSP, and CBD is based generally on clinical diagnostic criteria. Diagnosis based on MRI has limitations, and, therefore, we should reconsider our diagnoses, particularly during the early course of illness.
教育講演13
  • 吉田 邦広
    2011 年 51 巻 11 号 p. 865-867
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    With the increasing knowledge of the molecular bases for neurological disorders, neurologists are now often required to administer genetic testing and to present the resulting information effectively in clinical practice. In the neurologic clinical setting, genetic testing of affected individuals is usually taken into consideration for a correct diagnosis, but is rarely undertaken in healthy individuals to determine genetic risks for their life planning. Genetic counseling is indispensable for genetic testing because test results may cause serious distress for patients and their family members (referred to as "clients" in the counseling session). Genetic counseling is the medical process of communication that helps clients understand the nature of the genetic disorder and the options open to them in management and family planning. Through the counseling process, clients are given both the medical information and psychosocial support necessary for their own decision-making. Thus, the aim of genetic counseling is to support the client's decision-making process regarding genetic testing, and to avoid unfavorable actions after disclosure of test results. In the broad sense, genetic counseling is a part of ordinary clinical practice for patients with hereditary neurological disorders because neurologic clinical practice includes education and psychosocial support for patients. But clients seeking predictive genetic testing, which includes complicated ethical and psychosocial issues, should be referred to more specialized genetic counseling clinics that take a multi-disciplinary approach. The counseling process is not a one-way transmission of medical information by neurologists, but consists of two-way communication between patients and neurologists. It is therefore crucial for neurologists to master communication skills, particularly those involving active listening and empathic understanding, in order to conduct effective genetic counseling in clinical practice.
教育講演14
  • 曽根 三郎
    2011 年 51 巻 11 号 p. 868-871
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    In medical research, remarkable increase in collaboration with industry, public organizations such as universities, research institutions, and academic societies makes researchers to be more deeply involved with the activities of commercial entities. Activities of education and research, which are the responsibilities of academic institutions and societies, conflict with the interests of individuals associated with industrial-academic collaboration. Management of such conflict of interest (COI) is of much importance for academic institutions and societies to appropriately promote industrial-academic collaborative activities. Particularly, participation not only by healthy individuals, but also patients, is essential in the medical field as subjects of clinical research. For those involved in medical research, the deeper the level of COI with commercial entities, who are the financial or benefit provider, becomes serious, the more human rights of subjects could be violated, safety of life could be endangered, and research methods, data analysis and interpretation of results could be distorted. It is also possible that research may be unfairly evaluated or not published, even if the results are accurate, sometimes resulting in the ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions. According to the COI management guideline of the Japanese Association of Medical Science (JAMS), significance of COI management is discussed.
教育講演15
  • 本村 政勝
    2011 年 51 巻 11 号 p. 872-876
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies against acetylcholine receptors (AChR) and muscle-specific receptor tyrosine kinase (MuSK)/LDL-receptor related protein 4 which are AChR-associated transmembrane post-synaptic proteins involved in AChR aggregation. The seropositivity rates for AChR positive and MuSK positive MG in Japan are 80-85% and 5-10%/less than 1%,respectively. The incidence of late-onset MG, defined as onset after age 50 years, has been increasing worldwide. A nationwide epidemiological survey in Japan also revealed that the rates of late-onset MG had increased from 20% in 1987 to 42% in 2006. In 2010, a guideline for standard treatments of late-onset MG was published by the Japanese Society of Neurological Therapeutics. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction and approximately 60% of LEMS patients have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical pictures of Japanese LEMS patients are as follows; male dominant sex ratio (3 : 1), mean age 62 years (17-80 years), 61% of LEMS have SCLC, and the remaining are without cancer. In less than 10% of cases there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS) as well, often associated with SCLC. Most patients benefit from 3, 4-diaminopyridine plus pyridostigmine. In paraneoplastic LEMS, treatment of the tumor often results in neurological improvement. In non-paraneoplastic LEMS, prednisone alone or combined with immunosuppressants are treatment options. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.
教育講演16
  • 清水 利彦
    2011 年 51 巻 11 号 p. 877-880
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    片頭痛の一部の症例では時間経過とともに"episodic"な要素が消失し,連日性に拍動性であるがその他は緊張型頭痛に似た頭痛が出現するばあいがある.このような頭痛は慢性片頭痛といわれ治療に抵抗性で難治性片頭痛となることが多い.しかし難治性片頭痛に関する診断基準は作成されておらず,一般的には通常おこなわれる片頭痛の急性期および予防療法をおこなうが効果を示さない片頭痛と考えられている.診断には器質的障害による二次性頭痛や片頭痛急性期治療薬であるトリプタンや鎮痛剤の過剰使用によりおこる薬物乱用頭痛を除外する必要がある.難治性片頭痛に関する治療について"episodic"な片頭痛の予防療法として使用される薬剤であるカルシウム拮抗薬(ロメリジン),ベータ遮断薬(プロプラノロール),抗うつ薬(アミトリプチリン),抗てんかん薬(バルプロ酸,ガバペンチン,トピラマート)などをもちいるがこれらの薬剤を複数組み合わせ少なくとも半年は経過をみることが必要である.
シンポジウム1 BADはどう定義し,対応するか;各国の考え方
シンポジウム2 アルツハイマー病の分子治療戦略:新しい視点を求めて
シンポジウム3 脱髄性疾患におけるグリア間およびグリア・ニューロン間相互作用の破綻
シンポジウム4 神経内科領域における前方向的コホート研究から見えてきたもの
  • 中村 治雅, 川井 充
    2011 年 51 巻 11 号 p. 901-902
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    遺伝性神経・筋疾患の病態解明が進み,治療薬開発に向けた研究の進歩はいちじるしい.しかし,希少疾患における臨床試験実施においては患者数が少ないため,対象患者数把握や患者リクルートが困難であり,国際的な患者登録が進められている.国内では,欧州の神経・筋疾患研究ネットワークとも協調の上で,患者自身による登録をおこなうジストロフィノパチー患者登録システム(Registry of muscular dystrophy:Remudy)が構築された.海外との協調した患者登録システムは,希少疾患における新規治療開発を促進する上での重要なインフラストラクチャーである.
  • 熱田 直樹, 中村 亮一, 渡辺 はづき, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 田中 章景, 祖父江 元
    2011 年 51 巻 11 号 p. 903-905
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    To investigate the longitudinal course of Japanese patients with Amyotrophic Lateral Sclerosis (ALS), we constructed a multicenter registration and follow-up system called Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS). Genomic DNA samples of ALS patients were stored and linked to the clinical information. We designed a telephone survey system using a clinical research coordinator (CRC) to check the score of the ALS Functional Rating Scale-R (ALSFRS-R) and the prognosis every 3 months. In January 2006, we began registering ALS patients, and, at present, 22 neurology facilities are participating in the JaCALS. Currently, 571 Japanese ALS patients are registered.
    From the longitudinal data of the 279 patients who were registered before September 2009, the older age at onset was a significant risk factor for not only earlier death or introduction of mechanical ventilation, but also earlier loss of speech, loss of swallowing function and loss of upper limb function.
    In collaboration with the RIKEN Center for Genomic Medicine, genome-wide association studies (GWAS) using 1,305 ALS samples from the JaCALS and BioBank Japan were conducted, which showed that ZNF512B gene was associated with susceptibility to ALS.
    The JaCALS has established an efficient registration and follow-up system with genomic DNA resources of ALS patients, and will contribute to identify ALS-associated genes and to promote clinical researches.
  • 清原 裕
    2011 年 51 巻 11 号 p. 906-909
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    An accurate population-based cohort study of dementia was begun in 1985 in the town of Hisayama, Japan. To examine secular trends in the prevalence of dementia and its subtypes, four cross-sectional surveys were conducted among Hisayama residents aged 65 years or older in 1985, 1992, 1998, and 2005. The prevalence of Alzheimer's disease (AD) significantly increased with time, while the prevalence of vascular dementia (VaD) decreased from the 1985 survey to the 1998 survey and then increased in the 2005 survey. In a 17-year prospective study of a total of 668 elder residents without dementia, elevated midlife and late-life blood pressure were significant risk factors for the late-life onset of VaD, but not for that of AD. A 15-year prospective study of 1,017 elder subjects, who underwent a 75-g oral glucose tolerance test, revealed that the age- and sex-adjusted incidence of VaD and AD significantly increased in subjects with diabetes than in those with normal glucose tolerance. Moreover, 2-hour post-load plasma glucose levels were closely associated with increased risk of VaD and AD. In a pathological study of Hisayama residents, higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were significantly associated with increased likelihood of neuritic plaques.
  • 市川 弥生子, 後藤 順, 中原 康雄, 三井 純, 辻 省次
    2011 年 51 巻 11 号 p. 910-913
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder which is clinically characterized by various combinations of cerebellar ataxia, Parkinsonism, autonomic dysfunction and pyramidal signs. MSA is known as a sporadic disease, however, multiplex families with MSA suggest a genetic predisposition to MSA. The advanced genome research will clarify the pathogenetic mechanisms of MSA, and the disease-modifying therapy of MSA may be available in the future.
    To clarify the natural history of MSA for the future therapeutic trials, and to elucidate the molecular pathogenetic mechanisms of MSA, JAMSAC (Japan MSA research consortium), a nationwide consortium, was established in 2003. In the view of the future therapeutic trial for MSA, it is essential to design appropriate end point, sample size, duration of the trial. And inclusion criteria are also important for effective therapeutic trial. We conducted a cross-sectional study on 225 MSA patients using unified multiple system atrophy rating scale (UMSARS). As inclusion criteria, we employed additional criteria based on specific MRI findings to recruit earlier stage patients. Sample size estimation from the longitudinal study suggested we need sensitive outcome measures beside UMSARS.
    JAMSAC is planning to a longitudinal study for natural history of MSA in Japan.
シンポジウム5 筋ジストロフィー新規治療法開発の最前線
シンポジウム6 Brain-machine interfaceはどこまで可能か?
シンポジウム7 Atypical types of dementia非典型認知症
シンポジウム8 痛みの最新の病態と治療
シンポジウム9 皮質下性血管障害の病態と治療
  • 冨本 秀和
    2011 年 51 巻 11 号 p. 940-942
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    Subcortical vascular dementia (SVD) is a subtype of vascular dementia which constitutes approximately half of vascular dementia in Japan. It is featured by hypertensive small vessel disease such as white matter lesions and lacunar infarctions. The clinical and pathological features of SVD are relatively uniform. White matter lesions may remain asymptomatic but may develop subcortical dementia and Parkinsonism, if neural network function is impaired severe enough. SVD and CAA are considered to be a subcortical and cortical counterpart of small vessel disease, respectively, and the latter is closely associated with Alzheimer's disease. Therapeutic strategy for SVD is classified to the remedies for vascular risk factors and anti-dementia treatment. Anti-choline esterase inhibitors and memantine may be beneficial for SVD patients, but are not approved as therapeutic agents for vascular dementia.
  • 小野寺 理
    2011 年 51 巻 11 号 p. 943-944
    発行日: 2011年
    公開日: 2012/01/24
    ジャーナル フリー
    The discovery of the causative gene for hereditary cerebral small vessel disease (CARASIL: Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) opens a new avenue for exploring the pathogenesis of cerebral small vessel disease. The causative gene for CARASIL is HTRA1 (high-temperature requirement A1). HTRA1 is a serine protease and inhibits TGF-β signaling in their protease activity-dependent manner. The CARASIL-associated mutant HTRA1s lost their protease activity and increase the TGF-β family signaling. However the precious molecular mechanism for inhibition of TGF-β signaling by HTRA1 has not been elucidated. We have found that HTRA1 aberrantly cleaved pro-TGF-β in an endoplasmic reticulum and the cleaved products were degraded by the endoplasmic reticulum-associated degradation pathway. The result reconfirms the importance of HTRA1 for TGF-β signaling. The study for Marfan syndrome, which is caused by the increasing TGF-β signaling in aortic artery, indicates that the angiotensin I receptor antagonist, a drug already in clinical use for hypertension, inhibits TGF-β signaling and ameliorates the disease progression in model mouse as well as patients with Marfan syndrome. In human brain, angiotensin I receptor antagonist also inhibits TGF-β signaling. Therefore angiotensin I receptor antagonist warrants investigation as a therapeutic strategy for patients with CARASIL.
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