Deterioration of Cough, Respiratory, and Vocal Cord Functions in Patients with Multiple System Atrophy.

The purpose of this study was to clarify changes in cough function in patients with multiple system atrophy (MSA). Seventeen probable patients with MSA were studied. Peak cough flow (PCF), respiratory function (percentage of vital capacity, percentage of forced vital capacity, and percentage of predicted forced expiratory volume in one second), respiratory muscle strength (percentage of maximal inspiratory mouth pressure and percentage of maximal expiratory mouth pressure), and maximum phonation time (MPT) were assessed. Walking ability, disease duration, possibility of air stacking, Unified MSA Rating Scale (UMSARS), and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III were also assessed. Data were separately analyzed for ambulatory and non-ambulatory groups categorized by Functional Ambulation Categories. PCF, respiratory function, respiratory muscle strength, and MPT were significantly lower in the non-ambulatory group than in the ambulatory group. On the other hand, no correlation between PCF and disease duration was observed. A significant number of patients in the non-ambulatory group were unable to hold their breath. The UMSARS and MDS-UPDRS Part III in the non-ambulatory group were significantly higher than in the ambulatory group. It was concluded that ambulatory dysfunction is associated with the decline of cough function and respiratory-related function in patients with MSA.

Effects of Rehabilitative Intervention for Augmenting Cough Function in Patients with Multiple System Atrophy.

Objectives: One of the causes of death in patients with multiple system atrophy (MSA) is aspiration pneumonia caused by cough dysfunction. This study aimed to identify an effective approach to improve coughing and to explore the establishment of criteria for the use of gastrostomy based on cough and respiratory dysfunctions. Methods: Eighteen probable MSA patients participated in the study. They were categorized into air stacking and non-air stacking groups. First, we investigated how the inspiration volume changes by applying maximum insufflation capacity (MIC). Second, peak cough flow (PCF) was measured by different cough augmentation methods: 1) spontaneous coughing (SpC); 2) SpC with MIC (SpC + MIC); 3) SpC with manually assisted cough (MAC) (SpC + MAC); and 4) SpC with MIC and MAC (SpC + MIC + MAC). Among these four conditions, PCF values were compared to determine the most effective approach for cough augmentation. Receiver operating characteristic analysis was performed on percent forced vital capacity (%FVC) to determine an index for discriminating PCF below160 L/min, which indicates a high risk of suffocation, involving SpC and SpC + MIC. Results: Inspiration volume increased significantly with MIC in both groups (P < 0.05), and PCF increased significantly with MIC in the air stacking group (P < 0.01). PCF could not be maintained at 160 L/min when %FVC fell below 59%, even when MIC was applied. Conclusions: PCF increases with MIC in patients with MSA. It may be meaningful to consider the timing of gastrostomy introduction based on the severity of cough and respiratory dysfunction.

[Drugs for Amyotrophic Lateral Sclerosis].

Riluzole and edaravone for the treatment of amyotrophic lateral sclerosis (ALS) are currently covered by insurance in Japan. Both have been shown to prolong survival and/or inhibit progression, but neither is a cure-all treatment, and the effects are difficult to realize. The data presented in clinical trials are not applicable to all patients with ALS; the risks and benefits should be explained carefully before use. So far, edaravone has been administered intravenously, but an oral form became available in Japan on April 17, 2023. For symptomatic treatment, morphine hydrochloride and morphine sulfate are insurance-covered alternatives.

[Video Works on Amyotrophic Lateral Sclerosis].

Amyotrophic lateral sclerosis (ALS) is known to many as a disease that is infrequent but causes progressive disability and death within three to five years if a tracheostomy ventilator are not used. The patient must choose whether to live with a crippled body or die, and is faced with the question of what kind of condition is considered "living". By watching a video that addresses this theme, we can grasp this question even more deeply.

Culturally Adapted Consensus Definition and Action Guideline: Japan's Advance Care Planning.

CONTEXT: A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making. OBJECTIVES: A consensus definition of advance care planning with action guideline adapted to Japanese society. METHODS: We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan. RESULTS: The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future. CONCLUSION: Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

Teaching "medical interview and physical examination" from the very beginning of medical school and using "escape rooms" during the final assessment: achievements and educational impact in Japan.

BACKGROUND: There is no consensus regarding the best time to teach two fundamental pillars of clinical medicine: medical interview and physical examination. We investigated the impacts of teaching the course "Medical Interview and Physical Examination" in Japan from the very beginning of medical school. In addition, we also evaluated the educational value of using "Escape Rooms", a series of timed, game-based scenarios using simulators, as a part of the final assessment of the course. METHODS: At the end of the course, the interview capabilities of 140 first year medical students at International University of Health and Welfare (Japan) were assessed by physicians who acted as simulated patients. Physical examination skills were assessed using the "Escape Room" team task method. Students also self-assessed their confidence in their physical examination skills pre and post "Escape Rooms." A day prior to the final assessment, students completed an anonymous course evaluation. RESULTS: The average global rating of the students' medical interview skills using a rating scale from 1 to 6 (1-fail 6-outstanding, no different from practicing junior physician's level) was 4.6. Twenty-two students scored the highest mark of 6. An average of 89% of "Escape Room" teams finished all the physical examination tasks correctly within the allotted time. All teams that could not finish in time completed all tasks correctly when given an additional 3 to 5 min. Students' self-assessed confidence in their physical examination skills increased from 49 to 73 (out of 100) pre and post "Escape Rooms." In the course evaluation questionnaire, 99% of students answered "this course enhanced their motivation" (response rate 89%) and 99% also answered "this course was interesting and useful" (response rate 86%). CONCLUSIONS: This descriptive study analyzing both quantitative and qualitative data showed that the course not only achieved the intended objectives of successfully conducting comprehensive medical interview and basic physical examination skills, but also enhanced student motivation. "Escape Rooms", used for the course assessment, in itself enhanced students' self-perceived physical examination skills and had an added educational value.

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [123I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants.

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) for Japanese ALS and FTD patients.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) patients might present with cognitive and behavioural abnormalities resembling frontotemporal dementia (FTD). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was developed as an easy to administer cognitive screen for detecting these symptoms. The aim of the present study was to develop and validate a Japanese version of the ECAS. METHODS: In this single centre observational study, 35 ALS patients and 28 healthy controls were enrolled. Three patients in the ALS group fulfilled the criteria for behavioural variant FTD (ALS-FTD) and the rest were grouped as ALS without FTD. Participants were subjected to the Japanese version of the ECAS. ALS patients were also subjected to the Montreal Cognitive Assessment, Frontal Assessment Battery, ALS Functional Rating Scale-Revised, and respiratory function testing. Demographic and disease characteristics (e.g., sex, age at examination, and years of education) were also recorded. RESULTS: Internal consistency and correlations with general cognitive screenings were sufficient in the Japanese adaptation. Executive functions were the most commonly affected ECAS domain, followed by fluency and language. Compared to control subjects, ALS patients without FTD had low scores in the ECAS ALS-specific functions but not in ALS-nonspecific functions. Meanwhile ALS-FTD patients markedly underperformed both in the ECAS ALS-specific and ALS-nonspecific functions. Furthermore, the Japanese ECAS score correlated positively with years of education and negatively with age at onset. CONCLUSION: The Japanese version of the ECAS is a valid and useful screening tool to identify multiple types of cognitive impairment in ALS patients.

Prescription pattern of anti-Parkinson's disease drugs in Japan based on a nationwide medical claims database.

INTRODUCTION: Parkinson's disease (PD) treatment should follow guidelines and be tailored to each patient. Large database analyses can provide insights into prescribing patterns. METHODS: Retrospective, cross-sectional study of patients (≥30 years) with PD diagnosis (ICD-10; schizophrenia/cerebrovascular disease excluded) using health insurance claims data (April 2008-December 2016) from the Japan Medical Data Vision database. Prescription patterns of anti-PD drugs were analysed by patient age and sex, calendar year, and overall. RESULTS: The analysis comprised 155,493 PD patient-years (56.1% women, mean 73.4 years). Patient number increased each year, mainly because of database expansion. L-dopa as monotherapy was the most common prescription (22.7% of patient-years); non-ergot dopamine agonists (DAs) were also common (7.6% as monotherapy, 6.8% with L-dopa). Monotherapy was prescribed for ~50% of patient-years, two drugs for 14.1%, and at least three drugs for 18.4%. Consistent with Japanese guidelines, L-dopa was mostly prescribed to older patients (≥60 years), whereas non-ergot DAs were mostly prescribed to middle-aged patients (peak at 50-69 years). Between 2008 and 2011, L-dopa prescription decreased while that of non-ergot DAs increased; this pattern reversed between 2012 and 2016. CONCLUSION: These results indicate that Japanese clinicians are adhering to Japanese guidelines and tailoring anti-PD treatment to individual patients.

[Basics of Clinical Ethics].

Neurologists encounter patients who develop diseases that suddenly change their life one day, such as stroke, and diseases that are difficult to cure and progressive, such as intractable neurological diseases. There are many types of ethical issues, including the choice of medical intervention, caregiver conflict, genetic disease issues, end-of-life issues, etc. In this article, I will describe the matters advocated in general clinical ethics and discuss the interpretation and application in the field of neurology based on my own experience. The issue is why clinical ethics is necessary, methodologies and systems for dealing with ethical issues, four principles of clinical ethics, Jonsen's four contingency table, ethical consultation, application in neurological diseases, and issues to be noted.

[Home Care for Cancer Patients and Outreach from the Hospital].

Japan is entering a multi-dying era. In this situation palliative care is increasingly important. More than half of Japanese state that they want to stay at home even when facing the end of life, especially in cancer area. But in reality, more than 80% of people die in hospitals. People are not confident about caring and palliative care at home. Therefore, if palliative specialist can visit their homes to care for their patients and family and work with home visiting physician, they can back to home. This type of outreach also helps the doctors working in hospitals understand home care.

Adherence to treatment guideline recommendations for Parkinson's disease in Japan: A longitudinal analysis of a nationwide medical claims database between 2008 and 2016.

BACKGROUND: Adherence to the 2011 Japanese guidelines for treatment of Parkinson's disease (PD) in real-life practice is unknown. METHODS: In this retrospective longitudinal observational study, we examined patterns and trends in anti-PD drug prescriptions in 20,936 patients (≥30 years of age with newly diagnosed PD [International Classification of Diseases-Tenth code G20 or PD Hoehn and Yahr scale 1-5] and one or more prescriptions) using nationwide registry data between 2008 and 2016. Data are presented as descriptive statistics. RESULTS: Half (49.6%) of the patients received levodopa (L-dopa) monotherapy, followed by non-ergot dopamine agonists (DA) prescribed as monotherapy (8.3%) or with L-dopa (8.1%). Consistent with the guidelines, 75% of patients were prescribed within 13 days of initial diagnosis; L-dopa monotherapy was the most prescribed drug in patients ≥70 years of age, whereas non-ergot DA monotherapy was more likely to be prescribed than L-dopa in patients between 30 and 50 years of age. Inconsistent with the guidelines, L-dopa monotherapy was the most prescribed drug in patients between 51 and 69 years of age. Over the course of 4 years of treatment, the prescription rate of L-dopa monotherapy and non-ergot DA monotherapy decreased by 63.7% and 44.1%, respectively, whereas that of L-dopa and non-ergot DA combination therapy increased by 103.7%. Combination therapy with L-dopa, non-ergot DA, and monoamine oxidase-B inhibitors was gradually increased at a later stage. CONCLUSION: These results highlight that the state of PD treatment in Japan adheres to most of the recommendations in the 2011 national guidelines, but also precedes the 2018 guidelines.

Cognitive and behavioral status in Japanese ALS patients: a multicenter study.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression. METHODS: Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests. Caregivers were asked to complete the ALS-FTD-Questionnaire (ALS-FTD-Q), a behavioral screen. We defined severe cognitive impairment (MoCA < 21 or FAB < 11), mild impairment (11 ≤ MoCA ≤ 25 or 11 ≤ FAB ≤ 15), and normal cognition (MoCA > 25 or FAB > 15). Severe and mild behavioral impairments and normal behavior were defined by the ALS-FTD-Q scores. RESULTS: In 145 ALS patients, better cognitive scores were correlated with earlier age at onset, whereas a worse behavioral score was associated with a longer disease duration and higher level of anxiety and depression. Around seventy percent of all ALS patients showed mild (40-45%) or severe cognitive impairment with cognitive impairment outnumbering behavioral impairment fivefold. Cognitive functions were more impaired in patients with age of onset over 65 years, while behavioral scores were not related to age. CONCLUSIONS: Considering the high prevalence of in particular cognitive impairment, and the diversity of impairments, the cognitive and behavioral aspects of Japanese ALS patients should be given more attention clinically.

Recent transition of medical cost and relapse rate of multiple sclerosis in Japan based on analysis of a health insurance claims database.

BACKGROUND: In this study, we aimed to understand the trends in total and itemized medical expenses, especially of disease-modifying therapy (DMT), for multiple sclerosis (MS) in Japan through an analysis of health insurance claims data. METHODS: We analyzed a database containing health insurance claims data from hospitals that have adopted the Diagnosis Procedure Combination/Per-Diem Payment System in Japan. According to an algorithm based on diagnosis codes, data for all patients diagnosed with MS from April 2008 to July 2016 were extracted. Medical costs, rate of each medical treatment, and rate of relapses were analyzed by calendar-year. Medical costs in the month of relapse were compared with average medical costs per month of all MS patients by a cross-sectional analysis. RESULTS: Four thousand three hundred seventy-four MS patients were identified in the database. Total medical cost per patient per month (PPPM) increased from ¥87,640 (US$787.7 or €723.0 as of May 2017) to ¥102,846 (US$924.4 or €848.4) during the study period. This increment was mainly attributed to the growth in cost of outpatient DMT prescriptions, which increased from ¥23,039 (US$207.1 or €190.1) to ¥51,351 (US$461.5 or €423.6). In contrast, the rate of hospitalizations and relapses PPPM decreased during the study period (from 0.053 to 0.030, and 0.032 to 0.019, respectively). Medical costs in the month of relapse (¥424,661, US$3816.8 or €3503.1) were 3.57 times higher than the average monthly costs for all MS patients (¥119,021, US$1069.8 or €981.8), with the majority comprising hospitalization cost. CONCLUSION: Concomitant with the increased usage of DMT, the total medical cost for treating MS is increasing in Japan. However, rates of relapse and hospitalization have shown a decreasing trend. Although this study does not show the direct causality between DMT and reduction of relapse rates/fewer hospitalizations among MS patients, a reduction in hospital costs has been revealed concomitantly with the increasing prevalence of DMT.

Treatment and comorbidities of multiple sclerosis in an employed population in Japan: analysis of health claims data.

AIM: Use real-world data to investigate the treatment, comorbidities and prevalence of multiple sclerosis (MS) in an employed Japanese population. METHODS: Data from the Japanese Medical Data Center health insurance claims database were analyzed (January 2005-November 2014). Patients with claims associated with an MS diagnosis were identified (n = 494) and comorbidities and prescribed treatments were investigated. MS prevalence within the database was calculated for each calendar year (2011-2013) Results: IFN-ß and prednisolone were the most commonly prescribed treatments. Common comorbidities included astigmatism and gastric ulcer. Within the database, MS prevalence increased from 0.015 to 0.016%. CONCLUSION: MS prevalence increased from 2011 to 2013. Some comorbidities were considered unrelated to MS owing to how physicians use disease codes for reimbursement.

Pathological and immunoblot analysis of phosphorylated TDP-43 in sporadic amyotrophic lateral sclerosis with pallido-nigro-luysian degeneration.

Transactivation response DNA-binding protein 43 kDa (TDP-43) is a key protein of sporadic amyotrophic lateral sclerosis (ALS), and phosphorylated form of TDP-43 (p-TDP-43) is a major pathological protein that accumulates in sporadic ALS. p-TDP-43 is found not only in primary motor neurons, but often propagates to non-motor systems as well. However, pallido-nigro-luysian (PNL) degeneration (PNLD) is rarely associated with ALS. We describe here a 68-year-old ALS patient presenting severe PNLD. He had difficulty walking due to poor movement of his right leg, and was diagnosed as having Parkinson's disease because of akinesia. About 2 years after onset, weakness of his left hand and leg led to a diagnosis of ALS. Tube feeding and non-invasive positive-pressure ventilation were initiated. He died of respiratory failure at the age of 71. There was no family history of either neurological disorders or dementia. Neuropathological examination revealed severe loss of neurons and gliosis in the PNL system in addition to the upper and lower motor neuron system. p-TDP-43 pathology was widespread in the PNL and motor neuron systems and also in the amygdala and hippocampus where no significant gliosis or neuronal loss was detected. Synuclein pathology was not observed in the investigated areas. Immunoblot analysis of p-TDP-43 C-terminal fragments showed a type B band pattern consistent with sporadic ALS. This is the first case of ALS with PNLD, in which p-TDP-43 distribution was widespread in the hippocampal formation (Nishihira type 2 and Brettschneider stage 4), and the type B immunoblot pattern was confirmed. Our case indicated that the PNL system can be involved in the disease process in sporadic ALS cases, although rarely. We also reviewed previous autopsy cases of ALS with PNLD to clarify the clinicopathological features.

Prevalence, treatments and medical cost of multiple sclerosis in Japan based on analysis of a health insurance claims database.

Objective: To understand, through an analysis of health insurance claims data, the current treatment status and medical cost of multiple sclerosis (MS) in Japan. Methods: We analyzed claims data (January 2005-January 2016) from the Japan Medical Data Center Co., Ltd., identifying MS patients, except those with neuromyelitis optica, using an algorithm based on diagnosis codes. Prescription drug usage and medical costs for MS patients were analyzed. Results: A total of 713 MS patients were identified in the database. Between 2011 and 2015, the age-adjusted prevalence of MS in the database increased from 0.015% to 0.019%, and the female-to-male ratio increased from 1.70 to 2.03. The prescription rate for disease-modifying therapy drugs was higher in larger care settings. Prescriptions for fingolimod increased from 2011, with a concomitant decrease in prescriptions for interferon. The per patient per month cost for MS was ¥124 337 (US$1190 or €1084, as of October 2016). This was higher than the costs for Parkinson's disease (¥84 410), myasthenia gravis (¥82 944) and rheumatoid arthritis (¥53 843). However, the total per member per month cost for MS, which represents the population-based economic impact, was ¥25.2, which was lower than the parallel costs for Parkinson's disease (¥123.0) and rheumatoid arthritis (¥311.6) because of the low prevalence of MS in Japan. Conclusions: Using real-world data, we obtained up-to-date prevalence, treatment status and medical cost information for MS in Japan. The present results showed the efficacy of a real-world database to obtain the latest national trends for rare diseases, such as MS; this could have important implications for clinicians and policymakers.

Current treatment status and medical cost for multiple sclerosis based on analysis of a Japanese claims database.

OBJECTIVE: To assist policymakers as they reflect on treatment protocols and approaches for the efficient delivery of medical care for multiple sclerosis (MS) patients in Japan. METHODS: We analyzed data from a large Japanese health insurance claims database. Using an algorithm based on diagnosis codes, all patients with a diagnosis of MS were identified; patients having a non-MS demyelinating disease were excluded from the population. MS patient data were used for cross-sectional analysis carried out on the data collected at a certain period. We identified a total of 1808 MS patients, and we analyzed data for 1133 patients with an observation period of ≥6 months from October 2013 to September 2014. Newly diagnosed MS patients were identified within the MS patients, and their data were used for longitudinal analysis, tracking each patient over a period of time. RESULTS: The total per patient per month cost for MS was ¥93 542 (US$781, €695 as of October 2015). Disease-modifying therapy drugs costs constituted half of the overall medical costs. For newly diagnosed MS patients, hospitalization costs were the largest component in the initial month, while drug costs were the largest component more than several months after the initial visit. There was a positive correlation between relapse frequency and medical cost. CONCLUSIONS: These results provide up-to-date information on the demographics, medical treatment and cost status of MS in almost real-time by using a claims database. They suggest that claims data analysis can effectively support medical policymaking.

Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients.