European Committee for Treatment and Research in Multiple Sclerosis, the world–largest MS meeting, held in Paris in 2017 attracted more than 10,000 participants. This is mainly because a number of modifying drugs (DMD) for MS have been developed and approved in the last two decades. Interferon ß, an injectable, was the first approved DMD for MS. Thereafter, more potent DMD and oral DMD have been developed, and as of June, 2018, 6 DMD are now available in Japan while 15 DMD have been approved in Europe and North America. With multiple therapeutic options, we need to optimize MS therapy in view of various factors. Early diagnosis and treatment are imperative for improving the prognosis of MS. McDonald criteria have been revised for the diagnosis of MS, and several revisions for making earlier diagnosis were made in the 2017 version, but careful diagnostic workup to exclude alternative diagnoses is critically important. Neuromyelitis optica has been widely recognized after the discovery of aquaporin–4 antibody and should not be misdiagnosed with MS. Although escalation therapy has been a usual strategy for MS, adopting induction therapy and achieving “No Evidence of Disease Activity” are now seriously considered for better long–term outcomes. Challenges to be addressed in Japan include, 1) “Drug lag”. Pharmaceutical and Medical Devices Agency recommends participating in international clinical trials to resolve it. 2) MS–DMD–associated progressive multifocal leukoencephalopathy worries neurologists and calls for clinical vigilance. 3) Only patients with moderate or severe disabilities or those who have a mild disease but need high cost medical care are registered under the new law of “intractable diseases” including MS and NMO.

In 2025, 7 million baby–boomers generation will be late elderly people over 75 years old. At that time, the disease structure also changes drastically, and the treatment place also shifts from hospital to home. To prepare for such changes, the Japanese government is now hurried to establish a regional medical plan and district comprehensive care system.

The number of intractable diseases including neurological incurable diseases also increases. Especially the designated intractable diseases increased to 330. From now on, it is the time to support patients with neurological diseases in district comprehensive care system. To do this, home health care with neurological diseases is necessary through cooperation between a neurologist and a family doctor. In addition, it is necessary to create a mechanism to support neurological diseases with multiple medical care staffs. The challenges are described in this chapter.

Among various neurological diseases for which the neurology contributes to deal with, dementia and other age–related diseases are giving increasingly strong impacts on the persons with the diseases and the society along with the aging of the society in Japan.

In order to provide the necessary medical and long–term care for the patients with those diseases, the national and local governments have established the policies and introduced the framework for them including the long–term care insurance in 2000.

By 2025 when the baby boomers become age 75 and above, a structure called ‘the Community–based Integrated Care System’ will be expanded so that comprehensive provision of health care, nursing care, prevention, housing, and livelihood support are promoted. Through this system, the elderly and other people could live their lives in their own ways in environments familiar to them, even if they become heavily in need for long–term care.

The progression status varies place to place ; large cities with stable total population and rapidly growing population of over 75, and towns and villages with decrease of total population but gradual increase of population over 75.

As the number of elderly people with dementia is estimated to increase, expansion of the Community–based Integrated Care System is important to support community life of the elderly with dementia. The national government established Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan) for the further support in 2015.

It is necessary for all of medical and long–term care providers including the specialists of neurology to participate in the movement to reinforce the network which is the most important part of the system.

With an increase with age in the incidence of neurological diseases, there are growing numbers of patients with neurological diseases including dementia. Systems of healthcare, nursing, and aged care that deal with neurological disorders have been diversified. Most noteworthy is the system called “home medical care coordinator” that began in 2017. In Japan, efforts have been made to create a shift among people towards understanding that “Anyone can have dementia and live with dementia.” Issues regarding how to support the patient at the end of life stage and his/her relatives with their decision–making process remain to be solved in future.

Since palliative care is defined as it is for all ages and all diseases and it should be supplied as a human right, all neurologists are required to provide quality palliative care for various kinds of neurological disorders including stroke, dementia, and motor neuron diseases, etc.

In order to attain the successful palliative care for stroke, what the care team should provide are 1) patient–centered and family–centered approach, 2) to make an effort to prognosticate more accurately, 3) to plan and implement appropriate goals of care, 4) to be familiar with EBM of decision–making at the end–of–life, 5) to assess and manage pains and symptoms, 6) to have experiences with the end–of–life care in stroke, 7) to assist in referring a patients to the palliative care specialist if needed, 8) to be able to provide patients and their families with resource of spiritual care and bereavement care if needed, and 9) to actively engage in quality improvement project.

The Japanese government survey has demonstrated that the dementia patients will increase rapidly up to 9.53 million in 2040, with a 40% increase from 6 million at present. Two key issues in palliative care for dementia patients are artificial nutrition and hydration (ANH) and finding the best place to live at the end–of–life. Clinicians in Japan have recently begun realizing the importance of advance care planning (ACP) as well as the difficulty in implementing the end–of–life conversation effectively.

With a lack of “self-determination act” in Japan, a patient with amyotrophic lateral sclerosis (ALS) with total locked–in state (TLS) who possess an advance directive (AD) mentioning he/she would wish to withdraw from a mechanical ventilator once he/she becomes TLS, cannot be approved legally or socially of withdrawing from the mechanical ventilator. This ethical issue in Japan continues to be discussed among all disciplines nationwide.

Palliative care in a death–ridden society should be regarded as an issue of public health. Thus, medical professionals should educate the community people and collaborate with them to create a compassionate community where all people actively engage in helping and supporting the neighbors.

Future Japan is an unprecedented super–aged society, and also is expected that population decreases due to decline in a birthrate. From now on, the efficient medical treatment which thought Quality of life is important.

A useful neurologist has high communications skills and a suitable sense of ethics. A useful neurologist examines the whole body, because the nervous system has spread to the whole body. Therefore, a neurologist is also a general physician. The clinician should reply to the needs of the area rather than do the thing which he wants to do. Clinical practice of common disease ; stroke, epilepsy, dementia, and spinal disease is important. The neurologist has to bring up the younger generation as an expert group. The research which is useful for the medical treatment of an aged society and care is required. A neurologist also needs the management capability which other health professionals can work smoothly.

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.

Alzheimer型認知症（Alzheimer's Disease；AD）は，シナプス活動の低下による脳内回路破綻が認知機能障害を引き起こす原因ともされており，シナプス機能の改善を目指した治療法が注目されつつある．反復経頭蓋磁気刺激（repetitive transcranial magnetic stimulation；rTMS）は，シナプスの可塑性に注目した非侵襲脳刺激療法であり，ADを含む神経変性疾患へのニューロモデュレーション治療としての応用が期待されている．近年，海外からADに対する臨床研究の報告が増加しており，新たな治療アプローチとして注目されている．rTMSについて解説するとともに，ADに対するrTMSの最近の臨床報告について紹介する．

［目的］筋萎縮性側索硬化症（amyotrophic lateral sclerosis：ALS）に対するリハビリテーションには賛否両論がある．今回，edaravone点滴で入院した症例にリハビリテーション介入を行い，その有用性を検討したため報告する．［方法］上肢機能に脱力を認め，edaravone点滴を6クール施行したALS患者5例（男性2名，女性3名）を対象とした．Edaravone点滴1クールごとに，リハビリテーションを行い，各クールの点滴開始前後に簡易上肢機能検査（Simple Test for Evaluating Hand Function：STEF），握力，ピンチ力等にて上肢の動作機能を評価した．歩行評価に関しては，Timed Up & Go Test（TUGテスト）を用いた．それらの評価をもとにリハビリ訓練の立案やホームエクササイズ指導を各症例に行った．［結果］Edaravone点滴とリハビリテーションの介入によって数値データでは向上を認める結果となった．特に握力改善例が4例，STEF評価改善例が2例という結果で上肢機能の改善を認めた．握力低下の平均は−1.7kg，ピンチ力低下の平均は−1.2kgであった．また，歩行に関しては下肢装具療法を用いることで歩行時間の短縮を認める症例も見られた．［結論］Edaravone点滴とリハビリテーションの複合的治療介入ではALSの上肢機能を向上できることが推察された．

症例は45歳女性．2014年6月に全身性強直痙攣を起こし，徐々に会話量が減少し，不穏状態になった．8月に脳MRI FLAIR画像で海馬，扁桃体の高信号域，抗LGI–1抗体陽性を認め抗LGI–1抗体陽性辺縁系脳炎と診断した．ステロイドパルス療法，血漿交換療法を施行し軽快した．1カ月半後，大声で叫ぶなど精神症状で再発し，ステロイドパルス療法後に経口predonisoloneを導入し退院した．1年9カ月後，左上肢の舞踏運動，脳MRI FLAIR画像で右尾状核，被殻，淡蒼球に高信号域を認め再発と診断した．ステロイドパルス療法にて症状，画像所見は改善し，azathioprineを導入した．抗LGI–1抗体陽性辺縁系脳炎は稀ではあるが，再発を繰り返し認知機能低下をきたし，片側舞踏運動を呈することがある．認知機能低下を防ぐためにも，急性期加療の後にステロイドと免疫抑制薬の併用等の積極的な再発予防が必要と考えた．