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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system of unknown etiology. Based on a hypothesis that MS is caused by certain viral infections, the efficacy of interferon β was examined in patients and it became the first disease-modifying drug (DMD) approximately 30 years ago. Through the series of research utilizing experimental autoimmune encephalomyelitis, many other DMDs were later developed. With emerging insights on limitation of the animal model, newer treatment strategies are being developed based on pathological findings from MS patients. In the current article, the history of MS treatment and its future prospects will be reviewed and discussed.

The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this section I, we will discuss clinical and research topics of neurology categorized by the methodology, including genetic research, translational research, nucleic acid therapies, iPS research, and nursing/welfare.

The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this section II, we will discuss clinical and research topics of neurology categorized by the diseases. In each field, the hot topic of the disease was described by the expert.

We conducted the multicenter questionnaire survey targeting patients with Parkinson's disease (PD) in order to investigate the impacts on their daily lives and their requests to hospitals in the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mainly using open-ended questionnaire, we asked their anxiety, troubles they are facing, and requests toward hospitals in the pandemic of SARS-CoV-2. Two hundred fifth-eight PD patients answered the questionnaire. There were various opinions about anxiety such as "PD patients are susceptible and vulnerable to SARS-CoV-2" (36.8%). Concerning the troubles in the pandemic, the most frequent answer was that they couldn't participate in the rehabilitation and elderly day care (38.4%). Relatively many PD patients requested telemedicine (29.5%), whereas some people hoped face-to-face medical care (8.1%). There were demands about the delivery of medications (50.0%), the establishment of telephone consultations (43.8%), resources for rehabilitation at home (43.8%). The medical care adapted to the anxiety, trouble and requests of PD patients will be required in the era when we have to live with SARS-CoV-2.

The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this document, the general part is 1) What is neurological disease? 2) Current status of neurological disease overcoming research, 3) Significance and necessity of neurological disease overcoming research, 4) Research promotion system for overcoming neurological disease, 5) the roadmap for overcoming neuromuscular diseases, 6) a summary version of these recommendations are explained using figures that are easy for the general public to understand.

A quinquagenarian woman visited our hospital due to experiencing headache around the right upper eyelid for the previous 2 months. T 2 -weighted MRI of the head showed multiple high-signal-intensity lesions in the corpus callosum and bilateral corona radiata. She was thought to have an autoimmune disease and was treated with steroid pulse therapy, but the light reflex of the right eye diminished and the patient developed inferior horizontal hemianopsia. T 2 -weighted orbital MRI showed an enlarged right optic nerve, a high-intensity signal in the superior half of the optic nerve, and an enhancing effect. She also tested positive for anti-aquaporin 4 antibodies, so she was diagnosed with neuromyelitis optica spectrum disorder (NMOSD). This case shows that headache can be an initial symptom of NMOSD and that clinicians should consider NMOSD when attempting to diagnose patients presenting with headaches.

We report an 18 year-old-male, who had been aware of decreased visual acuity for 6 months, newly presented with paresis and sensory disturbance in his right leg. On admission, his critical flicker frequency was reduced bilaterally, and his spinal cord MRI revealed T 2 -hyperintense lesions in cervical and thoracic cord with occasional contrast enhancements, but none of them were longitudinally extensive. There was no evidence of T 2 -hyperintense in his brain MRI. Anti-aquapolin-4 (AQP4) antibody was negative but the patient was positive for oligoclonal bands in his cerebrospinal fluid. The patient was tentatively diagnosed as opticospinal multiple sclerosis (OSMS). However, he later tuned out to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The 2017 revised McDonald criteria don't take anti-MOG antibody into account in detail as to how clinicians should deal with patients fulfilling the MS criteria when they were also positive for anti-MOG antibody, because of its difficult problem of independence. So, we need to accumulate knowledge about these cases.

Around a half of multiple sclerosis (MS) patients suffer from cognitive impairment such as attention deficit. A similar impairment is already observable in one third of patients with clinical isolated syndrome, suggesting that the symptom cannot be solely explained by the accumulation of demyelinated lesions. Recently, several studies indicated that demyelination and atrophy in specific regions of the brain are related to the cognitive impairment, although those patients with brain and cognitive reserves are resistant to the development of such symptom. Aging, male sex and smoking increases whereas certain disease-modifying therapy decreases the risk of cognitive impairment in MS. Together, the development of cognitive impairment in MS appears to be determined by the balance between specific aggravating and protective factors.

Spontaneous remyelination occurs in many early multiple sclerosis (MS) patients, however its capacity decreases as the disease becomes chronic. Even in those chronic MS patients, an enough number of oligodendrocyte precursor cells (OPCs) are preserved within the demyelinated lesions, suggesting that the differentiation arrest of oligodendroglial cells underlies the remyelination failure in chronic MS. We have previously reported that TIP30, a factor inhibiting nucleocytoplasmic transport within the cell, is responsible for the differentiation arrest in MS lesions. Overexpression of TIP30 in the preserved OPCs in MS lesions results in the failure of nuclear translocation of transcription factors necessary for oligodendroglial differentiation. Therefore, anti-TIP30 therapy to regain the nuclear access within the OPCs is necessary for sufficient remyelination in chronic MS patients. Moreover, inflammatory conditions surrounding OPCs may be involved in the efficient remyelination in early MS lesions, alternative stimulatory factor may therefore be mandatory to induce OPC differentiation into oligodendrocytes within the chronic lesion. We have previously reported that targeting FcRγ protein on OPCs may stimulate their differentiation and consequently remyelination in the chronic lesions. A timely collaboration of these two approaches may be required for successful remyelination and neurological recovery in chronic MS patients.