神経治療学
Online ISSN : 2189-7824
Print ISSN : 0916-8443
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33 巻 , 4 号
選択された号の論文の21件中1~21を表示しています
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Editorial(論説)
  • 桑原 聡
    33 巻 (2016) 4 号 p. 499-501
    公開日: 2017/02/28
    ジャーナル フリー

    The Japanese POEMS syndrome with Thalidomide (J–POST) Trial is a phase II/III multicenter, double–blinded, randomized, controlled trial that aims to evaluate the efficacy and safety of a treatment with thalidomide in POEMS (crow–Fukase) syndrome. In this editorial, thoughts, opinions, and efforts to perform this investigator–lead clinical trial are described. A clinical trials are tough work, requiring a large amount of time, effort, and money, but it also give a great achievement for patients with intractable disease, and doctors and medical staffs involved in the trial. The advantage for the investigators includes expanding motivation for better and update understanding of the disease, as well as growing as a physician. The idea for novel treatments is more likely to be arising from young neurologists. Definitely this approach is necessary for rare diseases. The Japanese Society of Neurological Therapeutics should play an important role in the spread of clinical trial with novel treatments.

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特集 神経疾患治療の進歩2015年
  • 桂 研一郎
    33 巻 (2016) 4 号 p. 502-505
    公開日: 2017/02/28
    ジャーナル フリー

    After the report of 5 major randomized controlled trials (ESCAPE, EXTEND–IA, SWIFT–PRIME, MR–CLEAN, REVASCAT), adding mechanical thrombectomy on the t–PA therapy was thought to be acceptable. Mechanical thrombectomy might come back to the front page of the acute stroke therapy guidline. With the elongation of t–PA therapy to 4.5 h after onset of the ischemic stroke, the new era started for the acute stroke therapy. Although the study showed good results for mechanical thrombectomy, it should be emphasized that those studies were built on the conditions of 1) the use of stent type device, 2) selection of the patients with MRI or CT, 3) shortening of the time to apply devices.

    The Japanese guidelines for the management of stroke 2015 was published. It involved important evidences, searched from more than 23000 references for the stroke therapy. The classification of evidence levels were also improved.

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  • 脇田 英明, 冨本 秀和
    33 巻 (2016) 4 号 p. 506-509
    公開日: 2017/02/28
    ジャーナル フリー

    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 pursued extensively. This progress has led to the development of numerous therapeutic strategies in the clinical testing. A long–term randomized controlled trial suggested the beneficial effects of multidomain lifestyle–based interventions to maintain cognitive functioning, Although humanized monoclonal antibodies that bind amyloid b failed to improve cognition in patients with AD, several other promising trials are currently ongoing. In patients with dementia with Lewy bodies, it has been reported that lack of interferon–β signaling causes α–synuclein pathology. In addition, new therapeutic strategies have been reported in prion disease and Huntington disease. This review overviews recent advances in basic and clinical research in dementia.

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  • 中嶋 秀人
    33 巻 (2016) 4 号 p. 510-514
    公開日: 2017/02/28
    ジャーナル フリー

    Recent advances in the treatment of neurological infections are described based on reports published in 2014.

    Cochrane Database Systemic Review reported the effect of adjuvant corticosteroid therapy in acute bacterial meningitis. Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. It recommended the use of adjunctive dexamethasone in patients with suspected or proven community–acquired bacterial meningitis, but only in high–income countries. The European research group reported causative pathogens, clinical characteristics, and outcome of adult community–acquired bacterial meningitis after the introduction of adjunctive dexamethasone treatment and nationwide implementation of paediatric conjugate vaccines. The incidence of adult bacterial meningitis has decreased substantially, which is partly explained by herd protection by paediatric conjugate vaccines. Adjunctive dexamethasone treatment was associated with substantially improved outcome.

    Following standard treatment with intravenous acyclovir for PCR–confirmed herpes simplex encephalitis (HSE), Effect of an additional 3–month course of oral valacyclovir therapy was evaluated as measured by neuropsychological testing 12 months later. However, they did not show a benefit of long–term valacyclovir therapy. Recent reports showed that some patients with herpes simplex encephalitis (HSE) developed autoantibodies against NMDAR, in especially relapsing HSE. The clinical and immunologic features of patients with immune–mediated relapsing symptoms post–herpes simplex encephalitis were assessed. The teenage and adult patients developed severe psychiatric/behavioral symptoms or refractory status epilepticus, however, all younger children developed choreoathetosis. As immunotherapy can be highly effective, prompt diagnosis is important.

    Microbiological confirmation cannot be obtained in approximately two–third patients with tuberculous meningitis. The epidemiological, clinical, cerebrospinal fluid, and imaging parameters among patients with tuberculous meningitis were assessed. Among 118 cases of tuberculous meningitis, there were 36% of definite, 50% of probable, and 14% of possible cases. Severe disability, cerebrospinal fluid cells >100 mm3, and basal exudates were significantly related to definite diagnosis of tuberculous meningitis. Microbiologically confirmed tuberculous meningitis is associated with poorer outcome.

    Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation. The immune pathological study showed that early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. An increased mortality from early ART would be immunologically mediated.

    The triple combination therapy interferon–α, valproic acid, and prednisolone in patients with HTLV–I–associated myelopathy/tropical spastic paraparesis (HAM/TSP) was evaluated. As the data showed that the triple therapy improved motor dysfunction of the lower extremities as well as reduced HTLV–I provirus levels in peripheral blood, it could be a potential as a new therapeutic tool for HAM/TSP patients.

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  • 藤岡 俊樹
    33 巻 (2016) 4 号 p. 515-517
    公開日: 2017/02/28
    ジャーナル フリー

    Recent advances and new evidences related to treatment for multiple sclerosis (MS) were reviewed. In year of 2015, glatiramer acetate has been approved in Japan. New biological reagents have been developed in these several years, however, it seems very important to reconsider self injection agents such as interferon beta 1a/1b, or glatiramer acetate. They are still working well and very valuable.

    From such point of view manuscripts especially regarding optimization of disease modifying therapy for MS were reviewed.

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  • 村上 秀友, 小野 賢二郎, 河村 満
    33 巻 (2016) 4 号 p. 518-521
    公開日: 2017/02/28
    ジャーナル フリー

    We review reports published in 2015 providing new information on management of Parkinson's disease (PD) and related disorders.

    We report here the outcome of this new medical management of PD. Coenzyme Q10 improved motor symptoms in PD patients with wearing–off phenomenon. Pioglitazone, which is shown to have a neuroprotective effect in pre–clinical study, and neurturin, a neurotrophic factor, did not show symptom relieve nor inhibit the disease progression. Multidisciplinary rehabilitation, multi–dimensional balance programme and repetitive transcranial magnetic stimulation improved balance, gait performance and motor function. For treatment of motor fluctuation, ADS–5102, an amantadine extended release capsule, and eltoprazine, a 5–HT1A/B agonist, reduced levodopa–induced dyskinesia. Opicapone, a catechol–O–methyltransferase inhibitor, reduced off time.

    In studies aimed at improvement of non–motor functions in PD, transcutaneous tibial nerve stimulation reduced lower urinary tract symptoms such as urgency and nocturia. Droxidopa improved orthostatic hypotension, but efficacy lasted only one week. Injection of botulinum toxin type A into the parotid glands was effective in reducing drooling. Patients with chronic pain reported significant relief with prolonged release, oral formulation oxycodone combined with naloxone. Meta–analysis for treatment of cognitive impairment in PD showed cholinesterase inhibitors, aside from memantine, were effective. Exercise training such as modified Fitness Counts (mFC) and Progressive Resistance Exercise Training (PRET) improved attention and working memory.

    For treatment of parkinsonian type multiple system atrophy, rasagiline ― shown to have neuroprotective effects in preclinical studies ― did not show clinical effectiveness for multiple system atrophy.

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  • 矢部 一郎, 佐々木 秀直
    33 巻 (2016) 4 号 p. 522-528
    公開日: 2017/02/28
    ジャーナル フリー

    We reviewed the recent advances in therapeutics of spinocerebellar degeneration and multiple system atrophy that were published in 2015. Various clinical trials were carried out in 2015. However, the therapeutic reports did not provide much evidence. Some interesting clinical trials were reported, and further developments are expected. The therapeutic studies investigating a new pathomechanism were reported in animal and/or cell culture studies. We expect that these results will be translated to patients with these disorders.

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  • 鈴木 直輝, 加藤 昌昭, 割田 仁, 青木 正志
    33 巻 (2016) 4 号 p. 529-532
    公開日: 2017/02/28
    ジャーナル フリー

    Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem and spinal cord. Only supportive care and riluzole are available worldwide to date. This review provides a general overview of preclinical and clinical advances in 2015 and summarizes the literature regarding emerging therapeutic approaches. The topics include research using next–generation sequencing, progress in the pathomechanism of C9ORF72–mutated ALS, therapeutic strategies on mitochondrial pathology, novel investigation of therapies from Japan, strategies focusing on growth factors and neuro–inflammations, therapeutic strategies using iPS cells. We also discuss about the biomarkers and the problems of the design of clinical trials.

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  • 高橋 育子, 佐々木 秀直
    33 巻 (2016) 4 号 p. 533-536
    公開日: 2017/02/28
    ジャーナル フリー

    The aim of this paragraph is to introduce recent advances in the studies of gliomatosis cerebri, intravascular lymphoma, lymphomatoid granulomatosis and neurosarcoidosis to neurological clinicians based on reports published in 2015. Any four are very rare, and their neurological manifestations are non–specific, hence they are difficult to diagnose, in early phases.

    Regarding gliomatosis cerebri, younger patients showed good performance scores before therapy, underwent combined chemotherapy and had good survival outcomes. Diagnosing intravascular lymphoma requires considerable labor because it does not form a mass. In 2015, cases where successfully detected by endoscopic biopsy and nasal biopsy, were reported. Both biopsies are minimally invasive and can be recommended hereafter. A rare case of a patient with primary cerebral lymphomatoid granulomatosis which caused various neurological symptoms and progressed to methotrexate–associated lymphoproliferative disease, suggests that clonal analysis of the specimens are of importance to plan a treatment strategy. In diagnosing neurosarcoidosis, analysis of angiotensin converting enzyme from serum or cerebrospinal fluid did not show accurate results even though they were much anticipated. In the treatment of neurosarcoidosis, immunosuppressannts, monoclonal antibodies and intravenous immunoglobulin therapy were proposed as part of a combination therapy or second line therapy.

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  • 桑原 基, 楠 進
    33 巻 (2016) 4 号 p. 537-541
    公開日: 2017/02/28
    ジャーナル フリー

    In 2015, several studies about CIDP with antibodies to paranodal proteins were reported. Of the 533 patients with CIDP, 13 (2.4%) had IgG4 antibody to contacin–1. Three of 13 patients showed subacute symptom onset. All of the patients presented with sensory ataxia. Six of 10 anti–contactin–1 antibody–positive patients had poor response to IVIg, whereas 8 of 11 antibody–positive patients had good response to corticosteroids. The clinical features of CIDP with anti–neurofascin–155 antibody were reported. Anti–neurofascin–155 IgG4 antibodies were detected in 18% (9/50) of CIDP patients. Anti–neurofascin–155 antibody–positive CIDP patients had younger onset age (p<0.0001), higher frequency of drop foot (p=0.0242), tremor (p=0.03), and DADS phenotype (p=0.0014). Greater cervical root diameter on MRI neurography (p=0.002) and higher CSF protein levels (p<0.0001) were observed. Improvement of polyneuropathy following autologous stem cell transplantation (ACST) for sixty patients with POEMS syndrome was reported. After ACST, the Neuropathy Impairment Score improved from 66 to 48 points at 12 months and to 30 points at most recent follow–up (p<0.0001). The mRS score improved from 3 to 1.5 (p<0.0001). VEGF levels decreased from 452 to 63.5pg/mL (p<0.0001). The ulnar CMAP improved from 4.3 to 7.6mV (p<0.0001) and CV improved from 34 to 51m/s (p<0.0001). The clinicopathologic features of 18 patients with folate–deficiency neuropathy were reported. Those patients presented with low serum folate levels but normal blood thiamine and serum cobalamin levels in the absence of chronic alcoholism. Folate–deficiency neuropathy was characterized by slowly progressive polyneuropathy with predominant involvement of the lower extremities, with a tendency to manifest as sensory rather than motor neuropathy and predominant deep rather than superficial sensory loss, which was different from thiamine–deficiency neuropathy.

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  • 山元 敏正
    33 巻 (2016) 4 号 p. 542-545
    公開日: 2017/02/28
    ジャーナル フリー

    Articles in 2015 on treatments for autonomic nervous system disorders were reviewed.

    1. Orthostatic hypotension (OH) : Droxidopa had an improvement in some clinical symptoms due to OH in patients with Parkinson's disease, multiple system atrophy, pure autonomic failure and nondiabetic autonomic neuropathy.

    2. Constipation : Polyethylene glycol and lubiprostone were effective for the constipation due to slow colonic transit in PD. Management of constipation secondary to defecatory dysfunction due to pelvic floor dyssynergia could be done by levodopa or apomorphine injections, botulinum toxin type A injection into the puborectalis muscle.

    3. Postural tachycardia syndrome : Inspiratory resistance through an impedance threshold device improved heart rate control in patients with postural tachycardia syndrome during upright posture.

    4. Vasovagal syncope : Non–pharmacologic treatments including physical counterpressure maneuver and tilt–training and pharmacologic treatments with beta–blocker, fludrocortisone, midodrine and serotonin transporter inhibitors were effective in patients with vasovagal syncope.

    5. Urinary disturbance : β3–adrenoceptor agonist mirabegron improved the symptoms of overactive bladder (OAB). Antimuscarinics such as solfenacin, imidafenacin, fesoterodine or oxybutynin patch, provided an improvement of OAB. Treatment with solifenacin plus tamsulosin improved the storage and voiding symptoms. Combination treatment with mirabegron and solifenacin improved OAB symptoms. Accupuncture was safe with significant improvements of overactive bladder symptoms. BoNT/A and A/Ona showed benefits in treatment of refractory OAB. Percutaneous tibial nerve stimulation and sacral nerve stimulation showed effectiveness for treatment of OAB.

    6. Hyperhidrosis : Oxybutynin for treating plantar hyperhidrosis and topical glycopyrrolate for treatment of facial hyperhidrosis were effective. A combination of BoNT/A, B and anticholinergics improved compensatory hyperhidrosis after sympathectomy. Video–assisted thoracic sympathicotomy for the treatment of palmar and axillary hyperhidrosis showed the long–term effectiveness. Sympathotomy by clamping at T3 was less effective in reducing the primary symptom of postoperative palmar sweating, but induced less compensatory sweating than did sympathotomy by cutting at T3. Tumescent suction curettage was an effective and safe treatment for axillary hyperhidrosis.

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  • 星山 栄成, 辰元 宗人, 平田 幸一
    33 巻 (2016) 4 号 p. 546-549
    公開日: 2017/02/28
    ジャーナル フリー

    We reviewed major bibliographic references pertaining to headache (migraine and cluster headache) and epilepsy treatments, which were predominantly published in 2015.

    Calcitonin gene–related peptide (CGRP) plays a major role in the pathophysiology of migraine headaches. In 2014, the results of phase II clinical studies of two CGRP antibodies, LY2951742 and ALD403, were reported, and both antibodies demonstrated efficacy. TEV–48125, administered by subcutaneous injection every 28 days, seemed to be tolerable and effective, thus supporting its further development for preventive treatment of chronic migraine in a phase III trial. As these CGRP antibodies have high tolerability and cause few serious adverse reactions, they are expected to serve as the next generation of prophylactic drugs for migraine. A study demonstrated that simvastatin plus vitamin D was effective for preventing headaches in adults with episodic migraines. Given the ability of statins to repair endothelial dysfunction, this economical approach may also reduce the increased risk of vascular diseases among migraineurs. An open–label observational cohort study included patients with cluster headaches (11 chronic, 8 episodic), including 7 who were refractory to drug treatment. A device, known as the gamma–core, was used to treat and prevent individual attacks. Ten patients reduced their acute use of high–flow oxygen therapy by 55% and 9 reduced their triptan use by 48%. The prophylactic use of the device resulted in substantial reduction in the estimated mean attack frequency from 4.5/24h to 2.6/24h after treatment.

    Over the last year, several epilepsy studies published might soon influence our clinical decisions. A unique study this year was a clinical trial of bumetanide for the treatment of seizures in neonates with hypoxic–ischemic encephalopathy. Fourteen infants were included in the study ; they received bumetanide doses of 0.05mg/kg to 0.3mg/kg, together with phenobarbital. Eleven survived, but none had outcomes that met efficacy criteria.

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原著
  • 原 大祐, 山徳 雅人, 佐々木 直, 篠原 健介, 長谷川 泰弘
    33 巻 (2016) 4 号 p. 550-554
    公開日: 2017/02/28
    ジャーナル フリー

    症例は60歳男性.肺炎球菌性髄膜炎の診断で入院となった.髄膜炎は抗菌薬投与にて軽快するも,経胸壁,経食道心臓超音波検査で高度の大動脈弁逆流,逸脱を認めた.経過良好と考えられたが,第13病日より炎症所見の再燃,呼吸状態の悪化をきたし,急速に心不全症状が進行した.感染性心内膜炎による弁破壊,急性心不全と診断し,第22病日に大動脈弁置換術,大動脈基部形成術を施行した.術後経過は良好で,後遺症なく退院となった.肺炎球菌による肺炎,髄膜炎は適切な治療にもかかわらず時に致死的な感染性心内膜炎を合併することがあり,Austrian症候群として知られている.通常大酒家やcompromised hostなどに生じやすいとされるが,本症例ではこれらの危険因子はなかった.肺炎球菌感染では,危険因子の無い症例であっても本症を念頭において,心雑音の聴取などの注意深い身体所見の観察を行う必要がある.

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  • 桑原 拓己, 加藤 恵子, 武井 麻子, 田村 至, 森若 文雄
    33 巻 (2016) 4 号 p. 555-559
    公開日: 2017/02/28
    ジャーナル フリー

    症例は69歳の女性.Parkinson disease(PD)発症2年後に視覚構成機能障害,注意機能障害及び遂行機能障害(注意・遂行機能障害)などの高次脳機能障害が出現した.認知リハビリテーション(認知リハ)を4週間施行後,認知リハとrivastigmine patch貼付を4週間併用した.その結果,認知リハ開始4週後にtrail making test(TMT)–Bやbehavioural inattention test(BIT)の立体の大きさの把握が可能になる等,注意・遂行機能や視覚構成機能の改善を示した.また,治療開始8週後(rivastigmine patch貼付4週後)には,BITやAlzheimer's Disease Assessment Scale(ADAS)の形体の把握が可能となり,視覚構成機能の改善を示した.認知リハにより注意・遂行機能が,rivastigmine patchの追加により,視覚構成機能の改善を認め,この事がactivities of daily living(ADL)の改善に繋がったと考えられた.

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  • 渡邉 悠児, 鈴木 圭輔, 宮本 雅之, 宮本 智之, 平田 幸一
    33 巻 (2016) 4 号 p. 560-565
    公開日: 2017/02/28
    ジャーナル フリー

    閉塞性睡眠時無呼吸症候群(obstructive sleep apnea syndrome:OSAS)に慢性頭痛は高率に合併する.我々はOSASにおける一次性頭痛の合併頻度と持続陽圧呼吸(continuous positive airway pressure:CPAP)療法の効果について検討した.CPAP療法中のOSAS患者235例(男性190例,女性45例;平均54.8±11.6歳)を対象とした.一次性頭痛の診断は質問紙を参考に,面接法により国際頭痛分類第2版(International Classification of Headache Disorders, 2nd edition, ICHD–II)に基づいて行い,睡眠時無呼吸性頭痛の診断はICHD–3betaを用いた.OSAS 235例中105例(44.7%)に慢性頭痛があり,片頭痛18例(7.7%),緊張型頭痛55例(23.4%),群発頭痛1例(0.4%),その他の頭痛31例(13.2%)であった.頭痛のある群では,睡眠障害,日中の眠気,抑うつ症状が有意に多く認められた.慢性頭痛105例中39例(37.1%)に睡眠時無呼吸性頭痛を認めた.CPAP治療の効果があった片頭痛12例および緊張型頭痛33例のうち睡眠時無呼吸性頭痛の共存例はそれぞれ8例(66.7%),16例(48.5%)であった.頭痛のあるOSAS患者のうち睡眠時無呼吸性頭痛を除外した66例の中で,頭痛に対してCPAPの効果があった群(n=36)では,頭痛に対してCPAPの効果がなかった群(n=30)よりも一日のCPAP使用時間が有意に長かった.今回の検討ではOSASに慢性頭痛を高頻度に合併したが,睡眠時無呼吸性頭痛の診断基準を満たさない一次性頭痛においてもCPAP療法が有効な症例があることが明らかとなった.

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  • 鷲見 幸彦, 伊藤 健吾, 東海林 幹夫, 羽生 春夫, 尾内 康臣, 片山 禎夫, 渡辺 千種, 鈴木 啓介
    33 巻 (2016) 4 号 p. 566-571
    公開日: 2017/02/28
    ジャーナル フリー

    【目的】Lewy小体型認知症(DLB)患者の行動・心理症状(BPSD)に対するzonisamide(ZNS)の有効性について,単盲検プラセボ対照試験による探索試験を行った.【対象】2005年DLB国際ワークショップの診断基準でほぼ確実なDLB.プラセボ群7例 ZNS群6例【方法】ZNS100mgまたはプラセボ投与開始後2週及び4週目のNPIを主要評価項目として,投与開始後2週及び4週目のMMSE,NPI–Q及び投与開始後4週目のUPDRSのpart3を副次評価項目として検討した.【成績】両群の初期値に差はみられなかった.主要評価項目,副次評価項目のいずれにおいても有意差はみられなかったが,NPI総合得点の変化量をみると改善傾向を示していた.有害事象はZNS群1例で投与4週後幻覚,食欲不振がみられたのみであった.

    
【結論】症例数が少なく,統計学的有意差は得られなかったが,例数を増やして用量設定試験を試みる必要がある.

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