Recent advancement in studies on pathogenesis led to development of disease–modifying therapies such as nucleic acid therapies for neuromuscular disorders. Such therapies target disease causing genes and proteins, but therapeutic benefits in clinic is limited at a symptomatic stage of disease. To overcome this, strategies for prevention have been actively developed for neurodegenerative disease. Before manifestation of core motor/cognitive symptoms, preclinical and then prodromal stages exist during the progression of neurodegeneration. At preclinical stage, molecular changes occurs but symptoms are hardly detectable. At prodromal stage, heralding symptoms appear prior to manifestation of core symptoms. In cohort studies on at–risk subjects, mild motor/cognitive symptoms emerge ∼20 years prior to the onset of subjective symptoms in various diseases. For instance, non–motor symptoms including REM sleep behavior disorder occurs approximately 15 years before clinical diagnosis of Parkinson disease, which is made on the basis of subjective motor symptoms. The effects of disease–modifying therapy for preventing neurodegeneration is clearly shown in a clinical trial of nusinersen, a nucleic acid therapy of spinal muscular atrophy, for pre–symptomatic subjects, in which initiation of disease–modifying therapy before manifestation achieved potent therapeutic effects particularly in mild patients. Currently, cohort studies, biomarker research, and novel therapies are being developed to further prevent various neurodegenerative diseases.

We proved an overview of prevention medicine in neuroimmunological disease, especially focusing on multiple sclerosis (MS). Due to lack of large–scale primary–prevention studies, there are no concrete data on primary prevention for MS. Therefore, in this review article, we discussed risk factors for developing and worsening MS, including genetic factors (HLA), environmental factors (viral infection and sunlight exposure), and non–environmental factors (cigarette smoking). We also commented on secondary prevention therapies for MS currently available in Japan, including natalizumab, ofatumumab, fingolimod, siponimod, dimethyl–fumarate, glatiramer acetate, and interferon beta I a/b.

The number of patients with dementia is rapidly increasing, and it has become an important issue not only in medical care but also in society. As a countermeasure against dementia, prevention of dementia has been emphasized. Until recently, efforts have been made to improve lifestyle habits for the prevention of dementia. In Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), multidomain intervention of diet, exercise, cognitive training and vascular risk monitoring prevent cognitive decline in at–risk elderly people. In Lancet commission, modifying 12 risk factors was stated for the prevention of dementia. In World Health Organization guidelines, the 12 interventions for the risk reduction of cognitive decline and dementia were assessed. Recently, the disease–modifying therapies which affect the pathophysiological mechanisms in Alzheimer disease have been developed. The monoclonal antibodies, aducanumab, lecanemab and donanemab that selectively bind for amyloid β protein were effective for the prevention against the progression in early Alzheimer disease in phase 2 or 3 trials. Aducanumab and lecanemab have been approved by the US Food and Drug Administration. These new disease–modifying therapies might be promising preventive method in future.

Interventions before the onset of cerebrovascular disease in terms of preventive medicine, it is classified into 2 stages. As for zero–level prevention, it is a lifestyle intervention for the entire population. So–called primary prevention is an approach to a group of patients who already have vascular risk factors.

Zero–level prevention : To reduce the occurrence of risk factors for cerebrovascular disease, the goal is to educate the public widely on the impact of risk factors on the development of stroke and cardiovascular disease, and to manage lifestyle habits appropriately. These include salt reduction, smoking cessation, alcohol conservation, and improved nutrition and diet, including increased physical activity, and are tailored to each stage of life in all generations.

Primary prevention : Appropriate management of major risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and atrial fibrillation, to prevent their development. The goal of blood pressure control is set at <130/80 mmHg and a combination of calcium channel blockers, diuretics, angiotensin–converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), are recommended. In diabetic patients, not only proper management of blood glucose, but also strict control of cardiovascular risk factors such as blood pressure and dyslipidemia is important for stroke prevention. In patients with dyslipidemia, LDL–cholesterol should be controlled to <120 mg/dL. On top of diet, HMG–CoA enzyme inhibitors (statins), ezetimibe, proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are used. For patients with non–valvular atrial fibrillaiton, primary prevention of cardiogenic cerebral embolism is achieved with anticoagulants starting at a CHADS2 score of 1. Prefer DOAC over warfarin. Left atrial appendage closure devices are now also considered in atrial fibrillation patients at high risk of bleeding.

Migraine is one of the most disabling diseases with a significant socioeconomic impact. In Japan, five types of triptans have been approved since 2000. Furthermore, the development of lomerizine and the approval of valproic acid and propranolol for migraine prophylaxis have greatly improved the treatment of the patients with migraine. Clinical Practice Guideline for Chronic Headache 2013 was published by the Japanese Headache Society, which had prompted evidence–based migraine treatment. However, we cannot get the enough effects. Calcitonin gene–related peptide (CGRP) is a neuropeptide that has an important role in migraine pathophysiology and is a target for migraine preventive therapies. Monoclonal antibodies targeting CGRP (galcanezumab, fremanezumab and eptinezumab) and its receptor (erenumab) showed consistent efficacy for migraine prophylaxis with excellent safety profiles. The effects on refractory cases have also been reported, and it is expected to bring the good news to many patients who have not been effective with existing migraine prophylaxis, and a paradigm shift in migraine treatment is expected.

The discovery and approval of novel treatments and vaccines are altering the trajectory of neuroinfectious illnesses.

As for bacterial meningitis, the pneumococcal vaccine and Haemophilus influenzae type b vaccine have reduced the incidence of bacterial meningitis in children. The pneumococcal vaccine is now routinely administered to adults as well to prevent pneumonia, but problems of serotype substitution have arisen, including for children. Additionally, recently approved medications for the treatment of systemic myasthenia gravis and neuromyelitis optica spectrum diseases, such as eculizumab and labulizumab, increase the risk of meningococcal infection in adults and may result in meningitis. As a result, it is critical to immunize patients against meningococcal meningitis before administration and to describe the risks to the patient and family.

For tetanus, additional immunization with absorbed tetanus toxoid or concomitant use of human tetanus immune globulin should be taken into account, depending on the condition of the wound. According to an evaluation of contamination, wound depth, and consequences from neuropathy or ischemia, aggressive debridement should be taken into consideration for non–open wounds.

Vaccines for shingles have been approved for patients over 50 years of age, both live attenuated vaccines and genetically engineered vaccines. Given that both are successful in avoiding the disease's start, it is important to recognize the benefits and drawbacks of each and employ them appropriately.

The Japanese encephalitis virus, a flavivirus, is subject to routine vaccination in childhood, but it is known that the antibody retention rate declines in adults, and additional vaccination should be considered for those who work in rural areas in endemic areas. Although Japan has not licensed a vaccine for the tick–borne encephalitis virus, the administration should be taken into account if the individual will be living in an area where it is common or will be visiting a forest.

There is also disagreement over the effectiveness of long–term SARS–CoV–2 vaccines, and further understanding of the etiology is preferred.

＜目的＞慢性炎症性脱髄性多発ニューロパチー患者を対象に，経静脈的免疫グロブリン（intravenous immunoglobulin：IVIg）維持療法の点滴時間，患者満足度に関する前向き観察研究を行った．

＜方法＞20歳以上の患者23例において5% IVIg（n＝10）又は10% IVIg製剤（n＝13）の維持療法を定期的に受けていた2群において前向き調査を行った．両製剤の点滴準備時間と投与時間を測定し，患者のquality of life（QOL），治療満足度，労働生産性障害スコアを調査した．

＜結果＞総点滴時間は10% IVIgが5% IVIgの約半分であった（204分 vs. 437分；p＝0.0026）．QOL指標のEuroQol 5 dimensions 5–levelの平均QOL値は10% IVIgが5% IVIgより高く（0.74 vs. 0.57），5つのドメインのいずれのスコアも10% IVIgが良好であった．治療満足度，労働生産性の障害に関するスコアは両群で同程度であった．

＜結論＞患者が自覚する両製剤の治療効果に差はみられないが，10%製剤による点滴時間短縮の利便性は患者QOLを向上させるものと考えられた．

症例は76歳男性．2型糖尿病でinsulin glargine使用中にhemichorea–hemiballismusが出現し，夜間低血糖を繰り返していたことによる糖尿病性舞踏病と診断した．入院時の血糖値，HbA1cは正常範囲内であったが，繰り返す夜間低血糖が原因と考えた．高血糖による舞踏病様不随意運動はよく知られているが，低血糖や急激な血糖値の補正でも同症状を来すことが報告されている．一度の血糖値やHbA1cで異常を認めない場合にも，特にインスリンなどの低血糖発症リスクの高い治療薬を用いている症例では，低血糖による不随意運動である可能性を念頭に置く必要があると考える．

患者は50歳男性で，抗筋特異的チロシンキナーゼ（muscle–specific tyrosine kinase：MuSK）抗体陽性の治療抵抗性の全身型重症筋無力症（myasthenia gravis：MG）であった．中等度の筋無力症状は繰り返す免疫グロブリン静注とステロイドパルスの併用療法やcyclophosphamide静注療法に抵抗性であった．胸部造影CTにて前縦隔に索状と濃淡が不均一な造影陽性組織を認め，限局性の胸腺過形成を疑い拡大胸腺摘除術を施行した．摘出組織は脂肪組織と退縮胸腺で過形成胸腺は見られず，術後筋無力症状は悪化した．術後の免疫グロブリン静注とステロイドパルス併用療法は効果がなく，経口ステロイド薬と免疫抑制薬に加え血漿交換療法の繰り返しで抗MuSK抗体価が減少して筋無力症状が改善した．術前に明確な胸腺画像異常がない限り抗MuSK抗体陽性のMGでは拡大胸腺摘除術の適応はなく，本症例は治療抵抗性の抗MuSK抗体陽性のMG症例の治療法として，血漿交換療法の有用性を支持する症例であった．

症例は34歳女性．32歳頃から金銭管理が困難になり，33歳頃から駐車場に停めた車の場所を忘れるようになった．34歳頃から歩行時の浮動感が出現し持続し，歩行中にふらつき転倒したため前医を受診した．脳MRIで大脳深部白質の対称性の広範な異常信号域を認めたため，当科に紹介受診した．神経学的所見では下肢の深部腱反射は亢進していたが病的反射を認めなかった．神経心理検査ではMini Mental State Examination（MMSE）29点，Frontal Assessment Battery（FAB）14点であった．脳MRI T2強調像では，広範な左右対称性の白質病変を認め，白質病変内に線状の淡い低信号領域を認めtigroid patternが示唆された．神経伝導検査では末梢神経障害を認め，成人発症の白質ジストロフィーが疑われた．白血球中アリルスルファターゼA活性の低下を認め，ARSA遺伝子解析では，p.G101Dのヘテロ接合性変異とp.T411Iのホモ接合性変異を認めた．これらの結果により，異染性白質ジストロフィー（metachromatic leukodystrophy：MLD）と診断した．本例はMRIにおけるtigroid patternよりMLDを疑い診断に至った．Tigroid patternは，白質病変を呈する疾患の鑑別に有用と考える．

症例は妊娠13週の39歳女性．複視と嘔気を自覚し当科入院．神経学的所見として左眼瞼下垂，眼球運動障害を認めた．頭部MRIでは脳梁膝部から左前頭葉白質，右側頭葉内側，左中脳橋被蓋から左上小脳脚に異常信号域を認め，AQP4抗体陽性であったことからアクアポリン4抗体陽性視神経脊髄炎スペクトラム障害（neuromyelitis optica spectrum disorders：NMOSD）と診断した．治療としてステロイドパルス療法（intravenous methylprednisolone：IVMP）を実施したが，症状の改善は不十分であった．そのため免疫吸着療法（immunoadsorption plasmapheresis：IAPP）を追加したところ，症状は顕著に改善した．再発予防にprednisolone 10mg/日の内服を継続した．すべての治療を通して，妊娠継続・出産に関する有害事象はなく，母胎ともに経過良好であった．妊娠期間中のNMOSD治療に関しては，エビデンスが蓄積されておらず，個々の症例で異なるのが現状である．本症例では，妊娠期間中におけるIVMP，IAPP，prednisoloneによる免疫治療が有効かつ安全であることが示唆された．