In memoriam: Shukuro Araki, MD, PhD (1927–2025) pioneer of Japanese neurology and a global leader in familial amyloid polyneuropathy

Hiroshi Kawahara (1858-1918) graduated from Tokyo Medical School, the predecessor of the present Faculty of Medicine at the University of Tokyo, where he was strongly influenced by Erwin von Baelz. Soon after, Kawahara was appointed to a professorship of internal medicine at Aichi Medical School (now Nagoya University, School of Medicine). One of Kawahara's greatest contributions to Japanese neurology was the first publication of a textbook of clinical neurology written in Japanese. Published in 1897, it contains 469 pages of text with many original figures observed by Kawahara himself, covering a variety of organic and functional neurological diseases. Kawahara was well versed in many European neurological journals and writings and incorporated the essence of modern European neurology into this textbook. His masterpiece in neurology is the first description of brother cases worldwide of X-linked recessive spinal and bulbar muscular atrophy (SBMA) in 1897. Later, both basic research and clinical study were developed by researchers mainly at Nagoya University, and the pathophysiology of SBMA was clarified; eventually, disease-modifying therapy was first approved in Japan. Akira Takahashi, who recognized Kawahara's contributions and valued him as a founder of Japanese neurology, should also be appreciated.

ABSTRACT This study examines the master–disciple relationship between Jean-Martin Charcot and his Japanese pupil, Kinnosuke Miura, during Charcot’s last few years of life. Although Miura’s period of study under Charcot lasted only eight months, he revered Charcot as his lifelong mentor. Based on the biographical accounts written by Miura’s children and grandchild, we provide an overview of Miura’s life and examine his depictions of Charcot’s character, clinical style, and diagnostic approaches. We then explore why Miura continued to regard Charcot as his lifelong mentor, despite the brevity of his training. Finally, we discuss the profound impact of French neurology, as established by Charcot, on the evolution of clinical neurology in Japan.

Neurology in Japan did not develop from the separation of neuropsychiatry into neurology and psychiatry, which casts a shadow on the present situation of Japanese neurology. Functional neurological disorder (FND; hysteria) is a typical link between neurology and psychiatry. FND is a common disorder, which has been described from the ancient times and has also been the headstream of neurology. FND is not diagnosed by exclusion or by psychiatric causes, but should be actively diagnosed based on the neurological signs themselves (= positive signs of FND) as early as possible, with minimal ancillary tests. This opinion has been supported by the newest Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Many positive signs have been described. Assessment by a neurologist also becomes a treatment.

A questionnaire survey was conducted on 8,402 members of the Japanese Neurological Society to examine the current status and countermeasures for physician burnout, and 1,261 respondents (15.0%) responded. In this paper, we report the results of a comparison between male and female physicians. There was a significant difference in working and living conditions only for married people. It was confirmed that men work under stricter conditions in terms of working hours, and that the burden on women is heavier in the division of housework. Analysis using the Japanese Burnout Scale revealed no gender differences in overall scores, but as for factors related to burnout, in addition to factors common to both men and women, factors specific to men or women were clarified.

Cellular energetics play an important role in Parkinsons disease etiology, but no treatments directly address this deficiency. Our past research showed that treatment with febuxostat and inosine increased blood hypoxanthine and ATP in healthy adults, and a preliminary trial in 3 Parkinson's disease patients suggested some symptomatic improvements with no adverse effects. To examine the efficacy on symptoms and safety in a larger group of Parkinsons disease patients, we conducted a single-arm, open-label trial at 5 Japanese neurology clinics and enrolled thirty patients (nmales = 11; nfemales = 19); 26 patients completed the study (nmales = 10; nfemales = 16). Each patient was administered febuxostat 20 mg and inosine 500 mg twice-per-day (after breakfast and dinner) for 8 weeks. The primary endpoint was the difference of MDS-UPDRS Part III score immediately before and after 57 days of treatment. Serum hypoxanthine concentrations were raised significantly after treatment (Pre = 11.4 μM; Post = 38.1 μM; P < .0001). MDS-UPDRS Part III score was significantly lower after treatment (Pre = 28.1 ± 9.3; Post = 24.7 ± 10.8; mean ± SD; P = .0146). Sixteen adverse events occurred in 13/29 (44.8%) patients, including 1 serious adverse event (fracture of the second lumbar vertebra) that was considered not related to the treatment. The results of this study suggest that co-administration of febuxostat and inosine is relatively safe and effective for improving symptoms of Parkinsons disease patients. Further controlled trials need to be performed to confirm the symptomatic improvement and to examine the disease-modifying effect in long-term trials.

Modern Western medicine was introduced into Japan by a Dutch doctor Pompe van Meerdervoort in 1855. A German physician EOE von Balz devoted himself to educating medicine at Tokyo Medical School, the predecessor of the present University of Tokyo for 25 years. Hiroshi Kawahara and Kinnosuke Miura, pioneers of Japan Neurology, received their education by him. Kawahara first described X-linked bulvo-spinal muscular atrophy, and published the first Japanese textbook of clinical neurology in 1897. In 1902, Miura and others founded the Japanese Society of Neuro-Psychiatry, the forerunner of the present " Japanese Society of Neurology ". Both Seizo Katsunuma, Professor of Nagoya University, and Junnjiro Kato, Professor of Tohoku University, succeeded Miura's neurology. Miura investigated into the cause of beriberi, but ended in failure. Hasegawa's proposal at the Diet in 1894 that the Japan Government should found an independent department of neurology in the University of Tokyo was unfortunately rejected. There was no foundation of independent institute, department and clinic of neurology before World War II. Consequently Japanese neurology was on the ebb at that time.

In this paper, I make several proposals of what Japanese Neurological Society is able to do or should do in preparing future disaster in Japan. I mention several points separately.Patient education: Patients usually try to visit their hospital as soon as possible for the safety, especially in Japan. Is it true? The traffic jams actually blocked this action in March 11, 2011, which made more serious problems in some patients. We should ask them to prepare matters necessary for staying at home at least for a week when no medical emergency is present.Disaster prevention training: We should make a list of hospitals which accept emergent patients at disaster. We should have some methods of communication still active at disaster (internet, satellite phone) and make society network for communication and patient transportation. How to transfer required drugs to patients is another issue we should consider.Name tag: We sometimes treated unidentified patients in the disaster because the name tag or reference papers was gone or not specified to a certain patient. It is due to great mechanical power of injury or rains. For not detached from the patient and waterproofed, I recommend writing the patient's name on the chest with a permanent marker used in the triathlon when transferring the patients to other hospitals or other places.

Big earthquake and subsequent gigantic tsunami killed more than 20,000 peoples in Tohoku area of Japan on March 11, 2011. Neurological patients were one such victim because they are usually very vulnerable to such a huge tragedy due to their physical disability including artificial ventilator-support. On occasion of the last tsunami, most cases showed "all or nothing" to lose life or to survive, and there were only a little cases who needed emergency surgical treatment. In the very early period, some neurological patients required electric power to keep their life-supportive ventilator at evacuation house or even at home. In a week to a couple of months, many neurological patients needed continuous supply of their daily drugs which are essential to keep themselves in steady physical conditions and even for keeping their life. Based on such a background, Japanese Neurological Society (JNS) began to establish an emergent assistant network system from January 2012 in an attempt of supplying materials, drugs and energy power to neurological patients who require both under a very early period after any natural or political disaster and a later period. For example, JNS is going to apply IT system to connect distant but safer hospitals which accept emergent patients from the center of disastrous place. JNS may also send emergency medical team to the disastrous place to save neurological patients by passing necessary medicine and materials or moving patients to safer hospitals. JNS will make such a tentative program public on our website to collect many other constructive opinions from general member of the society and neurological patients. After getting those opinions, JNS will work to make the exact team for this purpose after general meeting of JNS on this May 2012.

Little is known about the diagnosis and management of restless legs syndrome (RLS) in Japanese neurology clinics. To validate the diagnostic criteria of the International RLS Study Group (IRLSSG) and the treatment algorithm of the Mayo Clinic in a Japanese neurology clinic setting and to clarify the features of Japanese patients with idiopathic RLS. Patients with RLS symptoms were examined by a neurologist and the assessment included neurological examination, tests for periodic limb movements (PLM) and dopaminergic response, and the clinical diagnosis was made according to IRLSSG diagnostic criteria. Patients diagnosed with idiopathic RLS were treated with dopaminergic agents and the efficacy was evaluated. The study subjects were 151 Japanese patients who presented with RLS symptoms. Idiopathic RLS was diagnosed in 113 patients, secondary RLS in 16 and RLS mimics in 22. The cause of RLS mimics was either myelopathy, radiculopathy or neuropathy in 11 patients. The mean age of patients with idiopathic RLS was 50.1 (SD 20.0) years, 63% were woman, 97% had daily RLS, 31% had family history (40% of the early-onset subgroup), 86% reported unpleasant sensations in the lower legs, 43% had PLM in the daytime suggested immobilization test, 81% suffered from insomnia, 49% had limitations of work and activities, 71% reported impaired mood, 27% had consulted physicians about their symptoms, 4% had been diagnosed with RLS, 73% improved after dopaminergic treatments, and 33% experienced complete remission. The clinical features of Japanese patients with idiopathic RLS were identical to those reported in western countries, which suggests that IRLSSG diagnostic criteria and Mayo Clinic treatment algorism are valid in Japanese neurology clinics. Both patients and physicians were not fully aware of RLS in this country. Neurological examination was important in excluding RLS mimics and making a diagnosis of RLS.

Appropriate assessments for medical techniques of clinical diagnostic examination have been one of long-standing issues in social insurance system in Japan. Assessments of those in the surgical fields in which the most of assessments are evaluated by surgical operations including related materials as well as surgeons' techniques, is rather easy to evaluate quantitatively. Comparing with this, medical fields including neurology, quantitative assessments of medical techniques either diagnostic or treatment is not so easy. In order to evaluate the burden in each technique in the medical fields, several research and surveillance have been performed. In terms of 'duration' of the medical techniques, there have been several date in favor of long duration techniques are evaluated as to be worth to cost higher. However, these data were criticized for the reasons of ignorance of patients' opinion such as satisfaction to the diagnosis and treatments. However, in neurological fields, "the neurological examination techniques" which has a consensus of taking long duration in each patient, was able to be evaluated as an independent item in medical social insurance system in 2008, albeit it is not as technique but as laboratory examination. Towards establishment of the economical basis for medical care, Japanese Neurological Association should have another identity of artisans' union as well as academic union.

The Japanese Society of Neurology was founded in 1960. The Department of Neurology was established at The Kyushu University Faculty of Medicine in 1963, and then The Japanese Neurology has advanced.

The history of the research of the prion disease is consolidated in 50 years after the Japanese neurology association starts. It was proven that it was an infectious disease from kuru that was a local disease of New Guinea, explained how CJD, the scariest disease for a neurologist, had come to be called a prion disease, and even a newly emerging prion disease referred in the future.

Roles of specialists in psychogeriatrics

The year of 2007 was a turning point of the treatment of Parkinson's disease (PD) in Japan. Severe adverse effects of dopamine agonists including valvular heart disease induced by ergots and sudden onset of sleep attacks induced by non-ergots, were disclosed, and treatments with agonists were reassessed. Good news were marketing of ropinirole, a new non-ergot agonist, in December 2006 and entacapone, the first catechol-O-methyl transferase (COMT) inhibitor in Japan in April 2007. Having faced these new situations, Japanese Neurological Association has started revising "the Guideline 2002 for the treatment of Parkinson's disease". Clinical trials of translational gene therapy for Parkinson's disease with adeno-associated virus (AAV) vector are now going on in four approaches: restoring dopamine synthetic capacity, protecting against cell death with trophic factors, interfering with the aberrant protein aggregation, and converting the subthalamic nucleus into an inhibitory, rather than an excitatory, structure. In Japan, gene delivery of the dopamine synthesizing enzyme aromatic amino acid decarboxylase (AADC) to the striatum of PD patients is going on in Jichi Medical University. New findings of the causative genes, environmental factors and molecular mechanism of PD have provided with new tools for developing new treatments. The big success of induction of induced pluripotent stem (iPS) cells from fibroblast has given an impact on cell therapy research of PD.

IN JAPAN, ALTHOUGH eminent surgeons have performed major operations while the patient is under general anesthesia since the end of the 18th century and the beginning of the 19th century, neurosurgical operations were performed only sporadically for many years after 1877. The Japanese Neurological Society was formed in 1948. Independent departments of neurosurgery have been established since 1962. The Board of Neurological Surgery was founded in 1966. The Fifth International Congress of Neurological Surgery, held in Tokyo in 1973, strongly influenced young Japanese neurosurgeons.

Parkinson's disease and degenerative language disorders