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.

In Alzheimer's disease, synaptic activity goes haywire and brain networks gradually falter. The non–invasive brain stimulation, which modulate the brain functional connectivity, may be a novel therapy. The repetitive transcranial magnetism stimulation (rTMS) is the application as the neuromodulation treatment to neurodegenerative disease including Alzheimer's disease. rTMS might be improved the cognitive function to increase the release of neurotransmitter and induce the synapse plasticity of the in the brain. The recent some reports suggested a favorable effect and safe of rTMS on cognitive function with Alzheimer's disease patients. These promising results remain to be confirmed in controlled studies based on a larger population size. Furthermore, well–designed studies warranted to determine the neural plasticity changes induced by rTMS.

Introduction :

The effect of rehabilitation on amyotrophic lateral sclerosis (ALS) is controversial. Therefore, we performed a combinative therapy with edaravone intravenous infusion and rehabilitation in patients with ALS, and evaluated the outcome of the treatment.

Method :

ALS patients with impaired functions of upper limb (n＝5) received the 6 courses of edaravone intravenous infusion for 2 weeks. During treatment with edaravone, the patients also underwent the rehabilitation. We measured the grip strength, pinch strength and Simple Test for Evaluating Hand Function (STEF) of patients, and determined the effect of the treatment. The gait function was evaluated using Timed Up & Go (TUG) test in the cases who can perform walking.

Result :

Treatment with edaravone infusion and rehabilitation improved some scores. Especially the improvement of grip strength was observed in 4 cases and that of STEF score in 2 cases, showing that functions of upper limb was ameliorated. Furthermore, the walking speed of a patient was increased by using lower extremity orthosis.

Conclusion :

The upper limb function of the ALS patients may be improved by the combinative therapy with edaravone intravenous infusion and rehabilitation.

A 45–year–old woman presented generalized convulsion followed by getting restlessness and less speech. Fluid–attenuated inversion recovery (FLAIR) images of brain MRI showed high intensity lesion in bilateral amygdara and hippocampus. Serum antibody screening showed positivity for anti–leucine–rich glioma inactivated–1 (LGI–1) antibody. We diagnosed her anti–LGI1 limbic encephalitis. She received both methylprednisolone pulse therapy and plasmapheresis and showed remarkable improvement of clinical symptoms and MRI abnormality. However, one month later, she showed recurrence with psychological symptom. After methylprednisolone pulse therapy, we started oral prednisolone for relapse prevention. About two years later, she presented left upper limb chorea, and FLAIR image of brain MRI revealed high intensity area in right caudate nucleus, putamen and pallidum. After methylprednisolone pulse therapy, we added azathioprine for relapse prevention. From the point of inhibition of cognitive impairment, we should consider aggressive immunotherapy, including oral prednisolone and immunosuppressant for anti–LGI–1 limbic encephalitis.