Recent epidemiological studies have shown the increases of neurological diseases. The progress of the treatment in neurological diseases, aging population and/or the progress of the health care system of intractable neurological diseases are contributing the increases. The door–to–door surveys in Japan clarified the prevalence rates and risk factors of some neurological diseases, such as dementia, parkinsonism, Parkinson's disease and mild parkinsonian signs. Here, we described the prevalence rates of these neurological diseases. In the near future, intervention studies of neurological diseases in Japan will progress more.
Immune–mediated neurological diseases such as multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), Guillain–Barré syndrome (GBS), and chronic inflammatory demyelinating polyneuropathy (CIDP) are called as neuroimmunological diseases. NMO, previously regarded as a variant of MS, has now been considered as a distinct clinical entity caused by anti–aquaporin 4 antibody. Usefulness of thymectomy for MG without thymoma has recently been shown by MGTX study. The antibodies to glycolipids and glycolipid complexes were present in the acute–phase sera from some GBS patients. The antibodies to paranodal proteins such as neurofascin 155 were positive in a subset of CIDP. Future studies, including those on the roles of proteoglycans, are necessary to elucidate the pathogenetic mechanisms of neuroimmunological diseases.
The central nervous system has very little if any potential for regeneration. That is why cell replacement therapy is needed for functional recovery in neurodegenerative diseases. Human embryonic stem cells emerged in 1998, and induced pluripotent stem cells in 2007. Thanks to the development of these pluripotent stem cells, we are now able to manipulate sufficient quantity and quality of donor cells for stem cell–based therapy. For Parkinson's disease, protocols to establish induced pluripotent stem cells and to induce dopaminergic neurons have been developed up to clinical grade, and preclinical data about the efficacy and safety of these cells exist for rodent and monkey models. Based on these efforts, clinical trials against neurodegenerative disease are soon expected.
Patients with Parkinson's disease (PD) may have impulsive–compulsive behaviors, such as impulse control disorder (ICD), dopamine dysregulation syndrome（DDS), and punding. ICD is a disorder characterized by impulsivity, i.e., a failure to resist temptation, urges, or impulses that may harm oneself or others. The ICDs frequently observed in patients with PD include pathological gambling, hypersexuality, binge eating, and compulsive shopping. Punding is a complex, prolonged, purposeless, and stereotyped behavior. The risk factors for developing such behaviors include a younger age of onset of PD and impulsive or novelty seeking characteristics. ICD may also be caused by dopamine agonists, with a higher risk associated with the dopamine D3 receptor subtype. Since behavioral disorders destroy the quality of life of patients with PD and their caregivers, early detection and appropriate management of symptoms are required. Changing or ceasing the use of dopamine agonists is recommended for improving ICD. In order to manage DDS, an improvement of “off” period is required, as well as limiting extra dosing of levodopa.
In 2015, the Japan Geriatrics Society published “Guidelines for medical treatment and its safety in the elderly 2015”. These guidelines described a revised list of potentially inappropriate medication, going through several processes of clinical questions, a systematic review, and formulated guidelines for applying the Grading of Recommendations Assessment, Development, and Evaluation system advocated by Minds 2014. These guidelines differ from conventional treatment guidelines in that safety is the main issue. This paper, referring to the guidelines, describes pharmacotherapy for insomnia, depression, and behavioral and psychological symptoms of dementia (BPSD) in the elderly.
Basically, it is important to perform non–pharmacotherapy before the pharmacotherapy for insomnia, depression, and BPSD in the elderly. It is also important to search for the causes of these symptoms and to treat them.
For pharmacotherapy for insomnia in the elderly, benzodiazepine drugs are in the list of drugs to be prescribed with special caution. However, non–benzodiazepine drugs also should be used with caution due to similar risks of fall and fracture. For elderly patients with depression, tricyclic antidepressants are in the list of drugs to be prescribed with special caution due to severe anticholinergic effects. SSRIs should be prescribed with special caution for patients who have a risk of gastrointestinal bleeding. Sulpride is in the list of drugs to be prescribed with special caution due to the adverse effects of Parkinsonism. It is reasonable to use cholinesterase inhibitors for depression, anxiety, and apathy, and use memantine for excitement and aggressive behavior in patients with Alzheimer's disease. Cholinesterase inhibitor is also useful for hallucination, delusion, and anxiety in patients with dementia with Lewy bodies. Typical anti–psychotics are in the list of drugs to be prescribed with special caution. Since atypical anti–psychotics have a risk of increase of stroke and mortality, they should be used at an effective minimum dosage and duration.
Autoimmune encephalopathies are clinically and immunologically heterogeneous disorders. Many different types of autoimmune encephalopathy have been discovered, and most common type may be Hashimoto encephalopathy in it. In clinical situations, we often recognize that patients with autoimmune encephalopathy are often misdiagnosed as exhibiting functional psychogenic movement, conversion, or somatoform disorders. We clinically analyzed 63 patients with autoimmune encephalopathy. Two–thirds of patients showed motor disturbance mostly with give–way weakness. About 70% of patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or fast neurologic pain. Most pain was distributed in manner that was not explainable anatomically. 27% of patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. We observed memory loss, PNES (psychogenic non–epileptic seizure), dissociative amnesia, hyperventilation, opsoclonus, epilepsy, or autonomic symptoms amongst our patients. Although give–way weakness, anatomically unexplainable pain, and strange involuntary movements were thought to be psychogenic, the presence of one of these three symptoms was indicative of autoimmune encephalopathy. As autoimmune encephalitis exhibits diffuse involvement with the whole brain, these symptoms were entirely understandable. Except for the presence of organic disease, most patients were classified into somatoform disorders or functional movement disorders. Without first excluding autoimmune encephalopathy, physicians should not diagnose somatoform disorders.
Iron is a bioactive metal essential for normal cellular functions. However, excessive iron leads to cell death because iron enhances oxidative stress due to the generation of highly cytotoxic hydroxyl radicals. Therefore, complicated cellular pathways have been developed to allow for the transport, trafficking and compartmentalization of iron in cells. The tissue iron content is critically regulated by several iron metabolic molecules.
Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of inherited neurodegenerative disorders collectively characterized by extrapyramidal movement disorders and abnormal iron accumulation in the deep basal ganglia nuclei of the brain. Ferritinopathy is one of NBIA and a progressive adult–onset movement disorder caused by mutations in the ferritin light chain gene. The major clinical symptoms are focal onset chorea or focal dystonia. It is characterized by iron and ferritin aggregate accumulation in brain and visceral organs, low serum ferritin levels, and brain MR images of T2 * signal loss in the dentate nuclei, thalami and globus pallidus. In advanced cases, the basal ganglia showed internal cystic degeneration. To date, nine causative mutations have been identified and eight of them are frame–shift mutations in the exon 4 of L–ferritin gene.
Bacterial meningitis (BM) can present as an acute fulminant disease that progress rapidly in a few hours or a subacute infection that progressively worsens during several days. The mortality rate with BM and the frequency of neurologic sequelae among those who survive are high. BM is thus a life–threatening neurological emergency. Early recognition, efficient decision–making, and rapid institution of therapy can be lifesaving. Empirical therapy should be initiated promptly whenever BM is a significant diagnostic consideration.
Infectious Diseases Society of America (2004) and European Federation of Neurological Societies (2008) reported initial management approach of BM. The guidelines for the clinical management of BM in Japan were published in 2007, and the revision was also published in December 2014. These initial therapeutic managements for BM differ for every country. The reasons for the different initial therapeutic management are based on the following strategies. The choice of specific antimicrobial agents for initial treatment is based on the current knowledge of antimicrobial susceptibility patterns of these pathogens in the area. For initial treatment, the assumption should be that antimicrobial resistance is likely. The choice of empirical antibiotic in BM may be influenced by a number of factors, including patient's age, systemic symptoms and local pattern of bacterial resistance. If there are no epidemiologic evidences in Japan, a committee investigates it and builds data in the revised Japanese guidelines 2014 for the clinical management of BM.
Although primary headaches are common and disabling neurological disorders, practical management of these disease still remain to be improved.
I introduced relevant recent advances of management of primary headache disorders and the International classifications of headache disorders by International Headache Society and its Japanese translation of Japanese Headache Society, and Japanese guideline for management of chronic headaches. I especially focused on acute treatment and prophylactic treatment of migraine headaches and management of trigeminal autonomic cephalalgia.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) are representative autoimmune peripheral neuropathy which can be adequately treated by immunotherapy. The first line treatment regimen in CIDP include oral corticosteroids, plasma exchange (PE), and intravenous immunoglobulin (IVIg). These three are equally effective in CIDP, and the second line or adjunctive therapies such as oral immunosuppressants are far much less effective. In MMN, only IVIg is designated as first line treatment and corticosteroids may worsen the limb weakness of patients. Therapeutic approaches against CIDP and MMN must be based on the accurate diagnosis, because several conditions such as sarcoidosis, Lyme disease, malignant lymphoma. HIV neuropathy may mimic CIDP and fulfil the diagnostic criteria for CIDP. Because the currently used diagnostic criteria for CIDP are intended to pick up patients as many as possible, we should be careful not to overdiagnose CIDP. However, at the same time, a lot of CIDP/MMN patients remain undiagnosed in Japan ; we should avoid underdiagnosis of these treatable neuropathies.
As the clarification of the nature of Parkinson's disease progresses, many drugs have been developed, and clinicians have been asked to make judgments as to their proper use. Until now, various dopaminergic drugs have been developed against the motor symptoms such as tremor, rigidity, akinesia and postural reflex disturbance as the main therapeutic targets. Recently, due to aging and prolonged disease duration of Parkinson's disease patients, it has become problematic and can not be ignored as a treatment target that includes autonomic symptoms such as constipation and orthostatic hypotension, REM sleep behavioral disorder (RBD), mental disorders such as depression, apathy, delusion/hallucination, performance impairment and cognitive disorders. Moreover, the manifestation of non–motor symptoms such as pain, fatigue, camptocormia, dropped head are focused as the cardinal symptom of Parkinson's complex. Further, these symptoms correlate well with the progression of α–synuclein pathological stage of Parkinson's disease reported by Braak et al. It is awaited to develop disease modifying drugs that suppress not only symptoms but also pathological progress itself. At the same time, it is also required to develop biomarkers that can be accurately used in the preclinical phase from the viewpoint of early detection and early prevention as well as risk factor analysis. In addition, intestinal microbiota dysbiosis and gut–brain axis via the vagus nerve are attracting attention as a new pathogenic mechanism of Parkinson's disease. In this presentation, I will present my personal opinion of various anti–Parkinson's disease treatment based on clinical evidences and its current use, as well as the molecular mechanisms concerning α–synuclein's pathology. Recent trial of immunotherapy targeting α–synuclein proteins and the suppression of the protein aggregation will also be outlined.
In recent years, outstanding progress has emerged in neuroimaging research of Alzheimer's disease (AD), which enables us to diagnose patients even in preclinical stages. However, it still remains uncertain to develop disease modifying therapy for AD. There are new concepts on the mechanism of tau and amyloid β accumulation, and its understanding may open an efficient way for therapeutic strategies for AD. This review focuses on the recent developments on the diagnosis and treatment of dementia.
Parkinson's disease has conventionally been considered as a movement disorder resulting from selective loss of dopaminergic neurons in the midbrain. In the past two decades, however, it is becoming recognized that non–motor symptoms such as constipation, orthostatic hypotension, and psychiatric symptoms develop concomitantly with or even precede the onset of motor symptoms. Braak hypothesis, which suggested that the initial manifestations of Parkinson's disease pathology develop in the medulla oblongata, and subsequently extend to the midbrain and further to the cerebral cortex, prompted neurologists to pay more attention to the non–motor symptoms and the extra–nigral lesions, i.e., involvement of the non–dopaminergic systems.
In this review, I start the discussion with the motor symptoms of Parkinson's disease, as current diagnosis of Parkinson's disease is still based on their presence. The second part of the review is focused on the neuropsychiatric symptoms of Parkinson's disease, which are, among the other non–motor symptoms, the most important factors determining hospitalization or nursing home placement.
Ischemic stroke, accounting for approximately 60% of all strokes, is classified into lacunar infarction, atherothrombotic brain infarction, cardiogenic cerebral embolism and others. Lacunar infarction and atherothrombotic brain infarction are mainly caused by arterial thrombus and cardiogenic cerebral embolism results from venous clot formation. In patients with acute ischemic stroke, neurological symptoms should be frequently assessed by NIH stroke scale (NIHSS) in order to perform thrombolytic therapy with recombinant tissue–type plasminogen activator (rt–PA). NIHSS is a simple scale for assessing neurological symptoms, which can be reliably performed by nursing staff. Blood pressure lowering therapy is basically not required in acute ischemic stroke ; however, blood pressure should be kept below 180/105mmHg and repeated blood pressure monitoring is needed, when intravenous rt–PA is considered.
Because recurrence and complicating diseases are not rare in acute ischemic stroke, in addition to vital sign monitoring, careful attention should be given to Cushing phenomenon, worsening of neurological signs, infection such as pneumonia, deep vein thrombosis, fall, convulsion and abnormal respiration. Assessment of swallowing function, including repetitive saliva swallowing test and modified water swallow test, and oral care are effective in preventing pneumonia. To achieve a favorable outcome of patients with acute ischemic stroke, the cooperation of all the medical staff involved in stroke medicine is needed. Particularly, appropriate nursing care is essential in detailed observation and management of patients with acute ischemic stroke.
Respiratory muscle paralysis is a hallmark of amyotrophic lateral sclerosis (ALS). Respiratory dysfunction in ALS should be appropriately predicted, evaluated, and managed with the goal of improving the patient's quality of life. Voice changes, anorexia, and nocturnal sleep deprivation may be early signs of respiratory decline. Forced vital capacity, peak cough flow, examination for nocturnal desaturation or hypoventilation, and phrenic nerve conduction study are useful as parts of a routine examination for assessing respiratory function. Noninvasive (NIV) and tracheostomy–invasive ventilation (TIV) are the most effective methods for improving patients' survival rate and quality of life. NIV prolongs the survival period for about one year and TIV for more than ten years. Clinicians should fully inform patients of the advantages and disadvantages of NIV and TIV at an early stage of the disease. If a patient elects not to use a ventilator, terminal and palliative care are needed. The important points to consider for the palliation of respiratory distress are (1) sufficient oxygenation, (2) preserving airway patency, and (3) drug therapy including use of opioids. Opioids in particular, which are still unfamiliar to Japanese neurologists, are crucial to successful palliative therapy in ALS patients.
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) targeting the oligodendrocytes and myelin through autoimmune mechanisms and shows relapsing–remitting clinical course. The patients with MS show variable neurological symptoms according to the involved lesions in the CNS. Due to the environmental changes of recent decades, the patients with MS are increasing. Recently, several new drugs for preventing relapses have been developed based on the understanding of MS pathophysiology.
Neuromyelitis Optica (NMO) is also a relapsing–remitting autoimmune disease of the CNS that mainly targets astrocytes. NMO patients preferentially show optic neuritis and myelitis which is characterized with longitudinally extensive spinal cord lesions on MRI. The pathophysiology of NMO is closely related to the anti–aquaporin 4 autoantibodies together with activation of complement.
The core features of MS and NMO are different and the treatments for the prevention of relapses are different.
In the inflammatory disease of the central nervous system, there are meningitis that inflammation is limited in a subarachnoid cavity and encephalitis that inflammation also occur in brain. Because of the high mortality rate and severe aftereffect particularly in encephalitis, early diagnosis and start of therapy are important. The diagnosis of encephalitis is made on the basis of clinical symptoms and cerebrospinal fluid abnormalities. Many cases often need to receive general care in the intensive care unit because of the serious condition. Bacteria, virus, tuberculosis, fungus, parasitic worm and prion protein are representative as causes of infectious encephalitis. Most of the non–infectious encephalitis is caused by autoimmune disease, including connective tissue disease, Behçet's disease, sarcoidosis, paraneoplasic encephalopathy and Hashimoto disease. According to fundamental differences for medical treatment, it is very important to distinguish infectiousness and non–infectiousness encephalitis. I explain the main point of the differential diagnosis, mainly on neurological examination, findings of radiological imaging and an examination of cerebrospinal fluid.
EMG is widely used for the diagnosis of neuromuscular disease. In this article, I emphasis on the recording principle of EMG and recording characteristics, especially rhythm of spontaneous activities. To understand the activity or prognosis of disease of patients, Fib/PSW is the most important findings. In ALS, fasciculation potential also reflects the active pathology of the disease.
Advanced clinical neurophysiology, or electrodiganosis, is not a research using novel examinations. This means a competence that can diagnose patients with neuromuscular symptoms based on clinical history and neurological findings, and thorough understanding of neuromuscular anatomy, as well as knowledge on individual neurophysiological tests. Neurological diagnosis should be established on neurological symptomatology, which in turn should be supported by neuromuscular electrodiagnosis. Lack of either symptomatology or electrodiagnosis is insufficient. Diagnosis based on imaging, skipping symptomatology and electrodiagnosis, will incur frequent misdiagnosis. History and neurological examinations are by far more critical as diagnostic tools in neurology than subspecialties of internal medicine. This is because the consciousness is in the center of the nervous system, which is the territory of neurology. When something happens within the nervous system, the consciousness can feel and explain what happens, which is the “history” and would help us to localize the lesion. Furthermore, the examiner can give stimulations to the body, evaluate the power of individual muscles, communicate with the patient using language, and thus can further narrow the lesion site : these are neurological examinations. The situation is quite different from disorders of internal medicine, such as diabetes or malignancy. Electrodiagnosis is closely linked with symptomatology because the nervous system conveys the information using electricity. Thus, electrodiagnosis may document direct counterpart of the weakness or sensory loss, and may accurately localize the lesion site along the nervous pathway. Among neurological findings, manual muscle testing (MMT) is especially useful for the neuromuscular electrodiagnosis. MMT is useful for the differentiation between amyotrophic lateral sclerosis and cervical spondylosis, especially cervical spondylotic amyotrophy (CSA), the latter is characterized by the accurate segmental distribution of weakness. MMT is also useful for the differentiation between CSA and neuralgic amyotrophy (NA) or that between pyramidal weakness and hysterical weakness.
Meta–analysis plays an important role in systematic review. It allows strong evidence to be obtained through combining the results (the differences between groups) from several related research studies. The method by which results are combined in meta–analysis has been developed in the statistics framework. On the other hand, imaging analysis has been applied in many studies of brain diseases. Meta–analysis of brain imaging studies is necessary mainly because of the small sample size typically used in individual brain imaging studies because of the acquisition cost. Meta–analyses have already been published for studies of neurological diseases, such as Alzheimer's disease and Parkinson's disease. Many methods have been developed and are reviewed in this article. One of the most popular methods is coordinate–based meta–analysis (CBMA), which combines coordinates obtained as the statistical results of each brain imaging study on the standard brain template. Since the coordinate represents only one of the regions (the peak), the original spatial map needs to be reconstructed for each study. The reconstructed spatial maps represented by multiple neighborhood coordinates are combined for several studies. Inferential statistical analysis is then applied to these maps to produce the final output of the meta–analysis, using permutation tests ; this is a similar approach to that used to create the statistical parametric map (SPM) in individual studies. This procedure is called an activation likelihood estimate (ALE) and there exist similar approaches such as kernel density analysis (KDA) and signed differential mapping (SDM). This article introduces the software that allows the implementation of these techniques, and also the database for the output of the brain imaging data analysis. Further development of the CMBA methodology, such as with the bias correction used in traditional meta–analysis, would be desirable. In conclusion, meta–analysis of brain imaging analysis would be helpful to obtain more credible evidence. The methodology is already established and available for implementation.
An aging society is progressing rapidly, so we face with serous problems about an old man living alone, elderly couples and nursing of the aged. Care management of depopulated areas is important to maintain the home welfare.
The number of doctors was regional differences in Japan, the western part of Japan is larger than that of Eastern part. Many areas have fewer practicing neurologists, we struggle to meet the demands of referring physicians for specialty physicians. In our county physician, hospital and clinic are advancing innovative approaches to speciality care efficiency, many of which will have been great relevance in other district. To get over neurological diseases, we cooperate closely with general physician, health nurse, druggist, PT, OT, social worker, ect.
As a result of the growing proportion of drivers aged 65 years and older, it is expected that the number of elderly drivers with dementia is increasing in Japan. Since June 2002, demented drivers have been prohibited driver's license by Public Safety Commission in Japan. However, we have no consensus guidelines for demented drivers. Following the law, the authority introduced a cognitive function assessment for the renewal when the driver is 75 years or older. They further started a policy in which physicians can voluntarily report their patients’ medical conditions, including dementia. Despite these law and policy improvements and the high expectations to the medical professionals regarding aging drivers, the current role of physicians is merely diagnosing dementia or not, and is lacking the guidance on safe driving for the drivers and their families. This paper suggests that several important medical and social factors might be considered for the management of drivers with dementia. Consensus medical guideline for demented drivers has to be developed.
People living with Parkinson's disease are stuck in the driving issues in Japan. Parkinson's disease is the most common movement disorder, in which dopamine replacement therapy (DRT) can relieve the severity of motor symptoms. There are two independent aspects in the driving problems, such as driving skills associating with motor deficits and sudden onset of sleep at the wheel associating with DRT. Instead of on road assessment of driving fitness, a driving simulator is increasingly used for clinical research and practice, which is expected supplying novel practical evidences. In contrast, DRT associating sleep problems are clinically delicate because DRT is essential for treatment of Parkinson's disease and is uneasy to be withdrawn even if sudden onset sleepiness was induced. Alternatively, people living with Parkinson's disease who need to drive in their daily lives are not so rare. There is neither legal restrictions in their driving nor practical guidelines of driving in Japan. This review summarizes such conflicting problems of the driving issues surrounding Parkinson's disease in Japan.
Nucleic acid medicine treatment is a promising technology and improving the efficacy of therapeutic oligonucleotides is still needed for its broad use. Although antisense oligonucleotides (ASOs) and short interfering RNA (siRNA) have been well known as nucleic acid medicine, pharmaceutical developments by using them are not completely free to be done due to patent protection. Therefore, we developed a new technology, third generation oligonucleotide. We named it heteroduplex oligonucleotide (HDO). In addition, our original drug delivery system (DDS) using glucose trasporter–1 (GLUT1) made great enhancement on delivery of oligonucleotides into the brain through blood–brain barrier (BBB). In this symposium, we show above two new technologies we have developed, and outline the nucleic acid medicine treatment for amyotrophic lateral sclerosis (ALS).
The development of better viral vectors, in particular those based on adeno–associated viruses (AAV), have led to successful results of clinical studies for hemophilia, congenital retinal blindness, aromatic l–amino acid deficiency, and Parkinson's disease. We recently developed tyrosine–mutant AAV9/3 vectors that can cross the blood– or meningeal–brain barriers. These vectors are expected to be utilized in treating neurodegenerative diseases, in which broad areas of brain must be transduced. In patients with sporadic amyotrophic lateral sclerosis (ALS), considerable proportions of spinal cord motoneurons express abnormal unedited GluA2 (a subunit of the AMPA receptor) at the glutamine/arginine site. This is primarily due to the downregulation of adenosine deaminase acting on RNA 2 (ADAR2). The excessive Ca2+ permeability of the AMPA receptors leads to motoneuron death. Gene delivery of ADAR2 using tyrosine–mutant AAV9/3 vectors in conditional ADAR2 knockout mice has significantly delayed the onset of the disease, extended the life span of the mice, abated their behavioral impairments, and promoted survival of the motoneurons without inducing any adverse effects. Based on these favorable outcomes in this proof–of–principle investigation in an ALS mouse model, we are planning a phase I/II clinical study. We have already initiated large–scale production of GMP–grade AAV vectors that express ADAR2 using the baculovirus system.
We discuss issues related to the following three aspects in the care of amyotrophic lateral sclerosis (ALS) : cooperation during the shift to home care, collaboration between care teams and medical organizations, and locations for long–term treatments after home care becomes impossible. In the shifting stage, the sooner referring patients to their primary doctor is, the better, and it is particularly important to provide information not only on their medical condition but also on their state of acceptance of the illness and their will about treatments such as artificial ventilation. During the home–care period, care teams in different fields have necessarily to collaborate. The ability of care managers is highly required so as to revise care plans according to disease progressions and potential problems and to organize home meetings for an integrated support. Also important are hospitalization for medical treatments, caring complications or respite care, visits of doctors in different branches, and the arrangement of medical agencies in these cases. When home treatments are no longer viable, relocation is necessary, but the reception of patients needing artificial ventilators or aspirators is still often hesitated. Some measures to differentiate the facilities that do or do not receive such high–care patients are considered mandatory, such as by the difference in their revenues.
Considerable problems against continuation of home care arise for ALS patients and their families who regret unwanted installation of tracheostomy positive pressure ventilation, as well as due to complications by frontotemporal lobar degeneration. Medical specialists need to provide sufficient information to help patients understand their disease and care conditions. Close communications between them and community staffs are essential for the patients themselves to decide how to be treated, based on their own perspectives on life and value, and to live and face the end of their life as they wish.