著者

荒木 信之 朝比奈 正人

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.5, pp.624-627, 2018 (Released:2019-05-15)

参考文献数

56

---

Article on novel development of neurological treatment published in 2017 were reviewed.Neurogenic orthostatic hypotension (OH) and postprandial hypotension (PH) : According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), abdominal binder, midodrine and droxidopa were assessed as strong recommendation for OH, and acarbose as strong recommendation for PH.Postural tachycardia syndrome (PoTS) : Ivabradine showed a possibility of effectiveness for PoTS, but.droxidopa did not improve significantly.Vasovagal syncope : Fluoxetine improved vasovagal syncope in patients with anxiety. Dual–Chamber pacing significantly reduced the recurrence of vasovagal syncope.Urinary disturbance : Solifenacine increased maximum cystometric capacity, and injection of onabotulinum toxin A reduced frequency of urinary incontinence.Chronic constipation : Lubiprostone increased spontaneous bowel movements in diabetic patients with constipation. Low dose linaclotide improved chronic idiopathic constipation. The phase II trial suggest that a clinically optimal dose of elobixibat is 10mg/day for Japanese patients with chronic constipation. Naldemedine significantly increased spontaneous bowel movements in patients with opioid–induced constipation.Anhidrosis : Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen were seen in patients with acquired idiopathic generalized anhidrosis (AIGA). The Japanese guideline of AIGA was revised in 2017.Hyperhidrosis : Percutaneous and oral oxybutynin administration improved hyperhidrosis.

著者

山田 正仁

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.157-161, 2018 (Released:2018-12-25)

参考文献数

20

---

Suspected non–Alzheimer's disease (AD) pathophysiology (SNAP) is a biomarker–based concept that is defined as a condition characterized by normal levels of amyloid–β protein (Aβ) markers (A−), but abnormal neurodegeneration (or neuronal injury) markers (N+). Recent studies indicated that SNAP is found in 17–35% of individuals with mild cognitive impairment (MCI). Similarly, 7–39% of patients with clinically probable AD dementia are negative for Aβ. Progression of cognitive impairment in individuals with SNAP is slower than that in A+N+ subjects with high likelihood of AD pathophysiology. Pathological backgrounds of SNAP are heterogeneous, including non–AD neurodegeneration, cerebrovascular disorders, and mixed pathologies. Non–AD neurodegeneration would include primary age–related tauopathy (PART), which corresponds to senile dementia of the neurofibrillary tangle type (SD–NFT) (tangle–only dementia) at the stage of dementia, and argyrophilic grain disease. Pathogenesis of AD in older people would be more complex than previously recognized, in which widespread Aβ and tau pathologies may be commonly preceded by PART pathology in the medial temporal lobe. Further, current trials of disease–modifying therapies for AD are reviewed. In addition, the author refers to a preventive intervention against dementia/AD with polyphenols under development by his group.

著者

田平 武

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.415-419, 2016 (Released:2016-11-10)

参考文献数

19

---

Alzheimer's disease is characterized by deposition of aggregated amyloid β protein and tau protein. Since active and passive immunization of Alzheimer model mice with aggregated Aβ or antibody to Aβ showed clearance of aggregated amyloid β deposits and improved memory and learning, immunotherapy targeting Aβ is being developed. Although a human trial of active immunization with Aβ and adjuvant QS21 was halted because of autoimmune encephalitis, the trial revealed that it is possible to clear Aβ deposits in humans. On this proof of concept, several clinical trials using monoclonal antibodies are on–going. Although solanezumab which recognizes Aβ monomer turned out ineffective in the primary endpoint, it showed significant beneficial effect in mild AD cases in the secondary outcome. Therefore, solanezumab is now on a large scale phase III trial in mild AD cases in the world. If it turns out to be effective, it will be the first disease modifying drug for AD in a few years. However, since monoclonal antibodies are extremely expensive, less expensive and long acting active immunization with Aβ peptide (a vaccine) will be widely accepted, if it is safe. If peptide vaccines are successful, more effective and sophisticated vaccines such as safe DNA and recombinant viral vector vaccines will be utilized in future.

著者

城倉 健

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.349-351, 2016 (Released:2016-11-10)

参考文献数

2

被引用文献数

1

---

Vertigo/dizziness of the central origin is usually associated with other neurological signs or symptoms such as motor palsy, sensory deficit, dysarthria, ocular motor palsy, limb ataxia, and truncal ataxia. On the other hand, vertigo/dizziness of the peripheral origin is characterized by positional torsional nystagmus (posterior canal benign paroxysmal positional vertigo), direction–changing horizontal nystagmus (lateral canal benign paroxysmal positional vertigo), or unidirectional horizontal nystagmus (other acute peripheral vestibulopathies). Direction–changing horizontal nystagmus and unidirectional horizontal nystagmus can also be seen in the central vertigo/dizziness ; these nystagmus are caused by a disruption and/or cerebellar disinhibition of the vestibular nucleus.Most peripheral vertigo/dizziness can be diagnosed by characteristic nystagmus, whereas neuroimaging study is necessary to confirm the diagnosis of central vertigo/dizziness. In the acute phase of vertigo/dizziness, antihistamine may be used to reduce symptom. For benign paroxysmal positional vertigo, the most common cause of vertigo/dizziness, canalith–repositioning maneuver is effective.

著者

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.3, pp.257, 2017 (Released:2017-10-14)

著者

鈴木 直輝 加藤 昌昭 割田 仁 青木 正志

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.518-522, 2018 (Released:2018-04-05)

参考文献数

58

---

Amyotrophic lateral sclerosis (ALS) is the progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem and spinal cord. This review provides a general overview of preclinical and clinical advances in 2016 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, neuroinflammation, autophagy, growth factor supplementation, axonal pathology in ALS. Clinical trials for ALS targeting on these pathomechanisms are on–going including intrathecal administration of hepatocyte growth factor (HGF).

著者

平田 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.35, no.2, pp.108-112, 2018 (Released:2018-08-31)

参考文献数

10

---

It is thought to be the most important area for therapeutics of the disease is the neurotherapeutics even in the future at 2040.We are facing on the super low birthrate and aged society in the present. Moreover, it will be continued and spread till around 2040.The cancer therapy and infection treatment must be important, however, these treatment will be completed without need. In contrast neurological disease patients who has long life duration are much important than them.In other words, the treatment region that is the most important to us in the future is neurotherapeutics.

著者

松原 悦朗

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.337-339, 2018 (Released:2018-12-25)

参考文献数

14

---

Alzheimer's disease (AD) represents the so–called “conformational disorders”. From a therapeutic view point, identification of targeting molecules which can trigger a complex downstream cascade (e.g., primary amyloid–relating process or secondary tau–related neuronal degeneration process) leading to AD dementia is a promising strategy. Evidence has shown that amyloid β (Aβ), particularly Aβ oligomers (AβOs), plays a causative role in Alzheimer's disease. If AβO cascade hypothesis is valid, therapeutic intervention targeting AβOs or for preventing the interaction between AβOs and tau is a promising treatment strategy for AD. We performed a hypothesis–driven, proof of concept study to prove the relevance of the in vivo Aβ oligomer cascade hypothesis using novel monoclonal antibodies specific to AβOs.We herein review our AβO–immunotherapy with particular focus in the confirmation the relevance of our therapeutic strategy, which resulted in the phase I trial in prodromal and early AD.

著者

布村 明彦 玉置 寿男

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.393-395, 2018

---

<p>Delirium is a common and serious acute neuropsychiatric syndrome and characterized by disturbance in attention and awareness, i.e., reduced ability to direct, focus, sustain, and shift attention and reduced orientation to the environment (Diagnostic and Statistical Manual of Mental Disorders, 5^th edition, American Psychiatric Association, DSM–5, 2013). While delirium is associated with higher rates of mortality and institutionalization, it remains underdiagnosed because of its diverse and multifactorial etiologies and widely variable presentation including hyper– and hypoactive subtypes. Multi–component approaches to modifiable risk factors are recommended for prevention of delirium, which include reduction of benzodiazepines and anti–cholinergic agents and environmental approaches towards normal sleep–wake cycle. Recently, a randomized placebo–controlled trial suggests preventive effects of ramelteon, a melatonin agonist, on delirium. Non–pharmacological strategies are central also for therapy of delirium, which focus on treating the triggering factors and addressing patient–specific and environmental risk factors that may contribute to the development or worsening of delirium. Antipsychotics such as risperidone, quetiapine, olanzapine, perospirone, and haloperidol can be used off–label to manage symptoms of delirium (Clinical Guideline for the Treatment of Delirium, 2^nd edition, Japanese Society of General Hospital Psychiatry, Practice Guidelines 1, 2015).</p>

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.S211-S252, 2018 (Released:2018-11-12)

著者

荻野 美恵子

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.3, pp.298, 2016

著者

冨山 誠彦 今 智矢 船水 章央 上野 達哉 羽賀 理恵 西嶌 春生 新井 陽 鈴木 千恵子 布村 仁一 馬場 正之

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.6, pp.642-645, 2017 (Released:2017-04-30)

参考文献数

10

---

Istradefyllineはウエアリング・オフのあるParkinson病患者の運動症状を改善する.しかし実臨床ではistradefyllineが有効でないこともしばしばあり,どのような患者にistradefyllineが有用なのか迷うことも多い.そこでウエアリング・オフがあり,オン時の運動症状が軽度なParkinson病患者(オン時のUPDRSパートIIIスコアが15点以下)を対象にistradefylline 20mg/日の有効性をオープンラベル試験にて評価した.14例の患者が8週間の試験を終了できた.Istradefyllineの追加投与により,オン時のUPDRSパートIIIスコアが有意に低下し,オフ時間が有意に短縮した.そのうちの13例は試験終了時にParkinson病症状の改善を自覚しており,istradefyllineの内服継続を希望した.ウエアリング・オフがあり,オン時の運動症状が軽度でドパ反応性が保たれている患者でのistradefyllineの有用性が示唆された.

著者

増田 曜章 植田 光晴 安東 由喜雄

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.158-161, 2016 (Released:2016-08-10)

参考文献数

11

---

Peripheral neuropathies are common disorders in the daily medical practice, and often cause weakness, numbness, pain, and autonomic symptoms. The several specific clinical laboratory tests are useful for the diagnosis of peripheral neuropathies. Nerve conduction studies are not useful for evaluating small fibre neuropathy, such as early stage of transthyretin–related familial amyloid polyneuropathy (TTR–FAP) characterized by involvement of small fibres such as Aδ and C fibres. To evaluate small fiber neuropathies, various autonomic function tests, such as laser–Doppler flowmetry, sweating tests using capsule type sweating ratemeter, electrogastrography, R–R interval study, 123I–MIBG myocardial scintigraphy, head–up tilt test, and intraepidermal nerve fiber density, are useful. TTR–FAP is an autosomal–dominant inherited disorder characterized by systemic accumulation of amyloid fibrils in various organs and peripheral nerves. To date, more than 130 mutations in the TTR gene have been reported. In TTR–FAP, several therapies have been developed in the recent decade. In addition to liver transplantation, tetramer structure stabilizers were developed. Also, gene silencing drugs are under clinical trials.

著者

村田 顕也

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.627-632, 2017 (Released:2017-04-30)

参考文献数

43

---

Immune–mediated necrotizing myopathy (IMNM) is recently defined subgroup of idiopathic inflammatory myopathies. IMNM is characterized by significant necrosis, with muscle fiber regeneration, but without or with little inflammatory cells on muscle biopsy. IMNM may be associated with myositis–specific autoantibodies against signal recognition particle (SRP), or against 3–hydroxy–3–methylglutaryl–coenzyme A reductase (HMGCR). Typical clinical features such as severe muscle weakness, highly elevated serum creatine kinase (CK) levels, as well as resistance to conventional immunosuppressive therapy. Severe limb muscle weakness, neck weakness, dysphagia, respiratory insufficiency and muscle atrophy were more frequently observed in patients with anti–SRP antibodies than that in with anti–HMGCR antibodies. The pathophysiological mechanisms of these diseases are poorly understood, and therapeutic strategies for treating patients have not yet been validated. Most patients in both types were initially treated with corticosteroids. Additional immunotherapies were needed in patients with anti–SRP antibodies. In addition, one third of IMNM therapy do not show known specific autoantibodies. This review provides an overview of this disease entity and focuses on its clinical features and immunotherapy.

著者

漆谷 真

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.72-78, 2017 (Released:2017-07-25)

参考文献数

32

---

TAR DNA–binding protein 43kDa (TDP–43) is a hallmark protein for amyotrophic lateral sclerosis (ALS), consisting of ubiquitinated and phosphorylated cytosolic inclusions in affected regions, namely TDP–43 proteinopathy. TDP–43 is physiologically located in the nucleus and plays diverse roles to maintain the RNA homeostasis, including pro–mRNA splicing, microRNA processing, non–coding RNA stabilization, mRNA transport, and the stress granule formation. Multiple cascades, basically causing a loss of these functions, have been proposed as TDP–43–linked ALS pathogenesis ; however, the mislocalization and aggregate formation of TDP–43 is considered to underlie various pathogenic pathways, ultimately leading to motor neuron death. A cell–to–cell spreading theory is attracting huge attention to explain the rapid regional progression of the paralysis, although in vivo evidence is still lacking. Recent knowledge highlights the stress granules as responsible sites of TDP–43 inclusion formation. The stress granules contain mRNA with chains of ribosomes, together with stress granule–related proteins, such as TIA1 and TDP–43, in which RNA translation is inhibited transiently until stress conditions are recovered. The disruption of this reversibility is implicated in the irreversible inclusion formation. A proportion of familial ALS patients carries genetic mutations in the TDP–43 gene, the most of which are concentrated at the carboxyl prion–like domain. Although the pathomechanisms regarding how mutant TDP–43 causes ALS remain elusive, it is reported that mutant TDP–43 impairs proteasome activity, resulting in the accumulation of aberrant TDP–43. Moreover, several genetic mutations other than TDP–43, such as C9ORF72, MATR3, hnRNP1, UBQLN2, STSM1, VCP, and OPTN cause TDP–43 proteinopathy. Importantly, transgenic mice expressing cytosolic TDP–43 show the similar phenotype of ALS, and the inhibition of the transgene restore the paralysis of the mice. These line of evidence indicate the huge potential of misfolded TDP–43 as a therapeutic target. Capturing the early structural conversion to pathogenic forms is a promising therapeutic avenue to overcome ALS.

著者

髙橋 牧郎

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.34, no.3, pp.182-187, 2017 (Released:2017-10-14)

参考文献数

18

---

As the clarification of the nature of Parkinson's disease progresses, many drugs have been developed, and clinicians have been asked to make judgments as to their proper use. Until now, various dopaminergic drugs have been developed against the motor symptoms such as tremor, rigidity, akinesia and postural reflex disturbance as the main therapeutic targets. Recently, due to aging and prolonged disease duration of Parkinson's disease patients, it has become problematic and can not be ignored as a treatment target that includes autonomic symptoms such as constipation and orthostatic hypotension, REM sleep behavioral disorder (RBD), mental disorders such as depression, apathy, delusion/hallucination, performance impairment and cognitive disorders. Moreover, the manifestation of non–motor symptoms such as pain, fatigue, camptocormia, dropped head are focused as the cardinal symptom of Parkinson's complex. Further, these symptoms correlate well with the progression of α–synuclein pathological stage of Parkinson's disease reported by Braak et al. It is awaited to develop disease modifying drugs that suppress not only symptoms but also pathological progress itself. At the same time, it is also required to develop biomarkers that can be accurately used in the preclinical phase from the viewpoint of early detection and early prevention as well as risk factor analysis. In addition, intestinal microbiota dysbiosis and gut–brain axis via the vagus nerve are attracting attention as a new pathogenic mechanism of Parkinson's disease. In this presentation, I will present my personal opinion of various anti–Parkinson's disease treatment based on clinical evidences and its current use, as well as the molecular mechanisms concerning α–synuclein's pathology. Recent trial of immunotherapy targeting α–synuclein proteins and the suppression of the protein aggregation will also be outlined.

著者

二宮 利治

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.S78-S78, 2016 (Released:2016-10-31)

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

---

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

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

---

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

富山 貴美

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.33, no.3, pp.428-432, 2016 (Released:2016-11-10)

参考文献数

9

---

Active and passive tau immunization has been shown to attenuate phenotypes in tauopathy model mice. So far, two tau vaccines and three anti–tau monoclonal antibodies have been subjected to clinical trials for patients with Alzheimer's disease or progressive supranuclear palsy. In the present study, we developed new monoclonal antibodies to hyperphosphorylated tau for future clinical use. Selected antibodies to pSer413–tau (Ta1505) and to pSer396–tau (Ta4 and Ta9) were injected intraperitoneally into aged mouse models of tauopathy once a week at 0.1 or 1mg/shot 5 times. Ta1505 antibody significantly improved memory in a dose–dependent manner, while Ta4 and Ta9 antibodies showed less effect. The cognitive improvement paralleled a reduction in the levels of tau hyperphosphorylation, tau oligomer accumulation, synapse loss, neurofibrillary tangle formation, and neuronal loss. Furthermore, Ta1505 antibody displayed suppressive effects against not only tau hyperphosphorylation but also Aβ oligomer accumulation in a different, aged mouse model of Alzheimer's disease. These results indicate that pSer413 is a promising target in the treatment of Alzheimer's disease and other tauopathies.