Severe fever with thrombocytopenia syndrome (SFTS) was first discovered as an emerging virus infection caused by a novel bunyavirus, which is classified to the Banyangvirus Genus in the Phenuiviridae Family (Huaiyangshan banyangvirus, former SFTS virus, SFTSV) in 2011. SFTS was also reported to be endemic not only to China, but also to Japan, South Korea, Vietnam, and Taiwan. The major symptoms of SFTS are gastrointestinal symptoms such as fever, general fatigue, nausea, vomiting, and diarrhea. Total blood cell counts revealed thrombocytopenia and leukopenia in patients with SFTS. Approximately seven years have passed since the discovery of SFTS patient in Japan. Forty to 100 patients with SFTS have been reported annually to the National Institute of Infectious Diseases from western part of Japan. Case fatality rate of SFTS is approximately 27–31%. The reasons behind the high case fatality rate might be that multiorgan failure, coagulopathy, and hemophagochtosis are induced in most SFTS patients. It was reported that an antiviral drug, favipiravir, was effective in the treatment of SFTSV infection in an animal infection model. SFTSV is circulating between wild animals and several species of ticks in nature, indicating that we cannot escape the risk of being infected with SFTSV and that SFTS will continue to occur in the endemic areas. Furthermore, it has been revealed that humans can also be infected with SFTSV through close contact with sick animals such as cats and dogs, both of which were also infected with SFTSV. Development of specific treatment and preventive measures with SFTS vaccines is necessary.

GNE myopathy is rare muscle disease affecting distal muscles like tibialis anterior. GNE gene, which encodes for a key enzyme in the sialic acid biosynthesis pathway, is mutated in the homozygote or compound heterozygote manner. The lack of sialic acid in skeletal muscle is the critical pathological process in GNE myopathy. GNE myopathy mouse model was established and supplementation of sialic acid improves the phenotype of these models. Phase 1 clinical trial in Japan was conducted at Tohoku University Hospital using aceneuramic acid, followed by the trials using slow release product of sialic acid. Phase II/III study was performed.

MELAS is a major clinical entity of mitochondrial diseases and is characterized by recurrent stroke–like episodes. Point mutations in the mitochondrial DNA including 3243A>G lead to deficiency of taurine modification at the first anticodon nucleotide, which results in failure to decode codons accurately. We previously showed that addition of taurine to the culture media alleviated mitochondrial function in patient–derived pathogenic cells. In a preliminary study, high–dose oral administration of 12g taurine completely prevented stroke–like episodes in two patients with MELAS for more than 9 years. Based on these preclinical and clinical data, we conducted a multicentre, open–label, phase III trial in which 10 patients with recurrent stroke–like episodes received high–dose taurine (9g or 12g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke–like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA^Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke–like episodes from 2.2 to 0.7 (p=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA^Leu(UUR) from peripheral blood leukocytes (p<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke–like episodes. In February 2019, Japan's Pharmaceutical and Food Safety Bureau granted marketing authorisation to taurine for the prevention of stroke–like episodes in MELAS.

Central sensitization is caused by alterations in the somatosensory system from high to low threshold pain hypersensitivity and is characterized by severe pain and diffuse pain distribution. It can contribute to pain chronification in several pain–related diseases. In migraine, several studies have suggested association of central sensitization and allodynia, cortical spreading depression and headache chronification. We discuss the role of central sensitization on migraine including our study utilizing Central Sensitization Inventory Japanese version.

Central sensitization is a neurophysiological state in which the central nervous system is overexcited in response to stimuli. It is thought to be associated with painful diseases such as migraine and fibromyalgia, as well as conditions that cause functional physical symptoms. In our study, we found that those with chronic headache had higher central sensitization and higher levels of central sensitization have been shown to reduce quality of life.

Migraine is a common and debilitating neurological disorder. In the prophylactic therapy of migraine, centrally–acting calcium blockers, antiepileptic agents, and tricyclic antidepressants are currently used. Nevertheless, alternative therapy is required to treat those who are intractable to these medications. Calcitonin gene–related peptide (CGRP) is abundantly expressed in trigeminal ganglion neurons. Blood CGRP concentrations are increased in some migraine patients, and intravenous administration with CGRP has been shown to induce delayed migraine–like headache attacks almost exclusively in migraineurs. Hence, attempts have been made to develop CGRP–based migraine therapy. Initially, small–molecule CGRP receptor antagonists were developed mainly for acute therapy. In addition, there was a motion to use monoclonal antibodies targeting CGRP or its receptor for migraine prevention. Large–scale placebo–controlled double–blind randomized clinical trials have demonstrated the safety and efficacy of these monoclonal antibodies. In this article, recent advances in migraine therapy based on CGRP–related antibodies and its perspective are discussed.

The appearance of sumatriptan in the 1990s was an epoch–making event. Since 2000, five types of triptans have become available for use in Japan. As a result, medical treatment for headaches has become more active and the quality of medical care has dramatically improved. Increasing experience with the use of triptan for the last 20 years has allowed medical professionals to overcome various problems such as the existence of nonresponders and adverse effects of triptan, and triptan treatment has thus matured. However, some patients with migraine do not benefit from the vasoconstrictive effect of triptan stimulated by the 5–hydroxytriptamine 1B receptor. The clinical application of selective 5–hydroxytriptamine 1F receptor agonists (ditans) and calcitonin gene–related peptide receptor antagonists (gepants) that can compensate for the shortcomings of triptan is now progressing, and we hope that such drugs will become the first–choice treatment among many patients with migraine.

In clinical trials of pharmaceuticals and medical devices, evaluation of efficacy is difficult due to the following problems ; there are variations between and within the therapeutic effects and onset of adverse events, possibility of bias based on study design, and clinical trial data is information from limited patient group and limited sample size in an environment different from usual medical care, etc. In clinical trials, statistical aspects are important in all stages of appropriate study plans, planned study implementation and data collection, analysis, and reporting of results. Therefore, cooperation with medical statistics experts is required from the planning stage. Needless to say, there is a need for more efficient and sensitive communication between statisticians and researchers, project managers, data managers, monitors and CRCs and support staff of clinical trial. In this paper, the 6 points that characterize the clinical trial design that statisticians are paying close attention to as a knowledge of statistics to plan the design are explained.

地域診療所での神経内科専門診療体制の現況を明らかにするために，厚生労働省平成30年医師・歯科医師・薬剤師統計の概況，兵庫県医療機関情報システムおよび複数のインターネット医療検索サイトを調査した．さらに2017年に開設した当院の診療実績を集計した．

全国の診療所勤務医103,836人中，主たる診療科として神経内科をあげたのは531人であった．2019年10月末日で，神経内科・脳神経内科・脳神経外科で検索し，県内で該当した診療所は172件あり，内訳は脳神経外科が63件，精神科が48件，内科他が32件で，神経内科は26件のみであった．神経内科のみを標榜する当院は，患者の7割がインターネット等からの直接来院であり，症状では頭痛が最も多く，しびれとめまいが次いだ．疾患別では，Parkinson病，認知症，てんかん，神経難病の順であった．今後は病院だけでなく診療所レベルでも神経内科専門診療の充実が求められる．

HAL^®医療用下肢タイプ（HAL）による歩行運動療法を継続したCharcot–Marie–Tooth disease（CMT）の1例を報告する．症例は36歳女性．20分/日のHALによる歩行運動療法を3日連続で実施したところ，歩行機能が改善した．その後，介入頻度を下げても歩行機能が維持され，自宅内での移動が四つ這いから独歩となり，日常生活動作も容易になった．HALによる歩行機能の再学習が歩行機能の改善に寄与したと考えられた．