A case of pure autotopagnosia following Creutzfeldt-Jakob disease.

A 69-year-old male (N.A.) with Creutzfeldt-Jakob disease showed pure autotopagnosia. We administered tests evaluating his ability to name his own body parts, to point to body parts (his own and examiner's), and to recognize positional relationships between his body parts by verbal questions and responses. We found impaired localization of the patient's own body parts by pointing and impaired recognition of positional relationships between his body parts. However, there was no impairment in naming his own body parts or in localizing the examiner's body parts. The results suggest a pure autotopagnosia in N.A. leading to an impairment of recognition of the spatial position of his body parts in a three-dimensional body representation within the egocentric reference frame. We were able to rule out the possibility that his pattern of performance could have been due to a disability in programming reaching movements of the arm.

A Cross-Sectional Study on Socioeconomic Systems Supporting Outpatients With Parkinson's Disease in Japan.

OBJECTIVES: We conducted a cross-sectional study to evaluate the socioeconomic systems supporting outpatients with Parkinson's disease (PD) in Japan. METHODS: The study was performed in 2013 at two private hospitals and one clinic in Hokkaido Prefecture, Japan. A survey was conducted with 248 consecutive PD patients, and the data from 237 PD outpatients were analyzed after excluding 11 patients who did not meet inclusion criteria. Monthly medical and transportation payments as a PD outpatient were selected as outcome variables, and their association with various explanatory variables, such as utilization of support systems for PD outpatients, were evaluated using logistic regression model analysis. RESULTS: After controlling for potential confounding variables, the utilization of the system providing financial aid for treatment for patients with intractable disease was significantly inversely associated with monthly medical payment among PD outpatients (OR 0.46; 95% CI, 0.22-0.95). Experience of hospital admission for PD treatment was significantly positively associated with monthly transportation payment (OR 4.74; 95% CI, 2.18-10.32). Monthly medical payment was also significantly positively associated with monthly transportation payment (OR 4.01; 95% CI, 2.23-7.51). CONCLUSIONS: Use of Japanese public financial support systems may be associated with reductions in medical payments for PD outpatients. However, those systems may not have supported transportation payments, and higher transportation payments may be associated with an increased risk of hospitalization.

Analysis of resources assisting in coping with swallowing difficulties for patients with Parkinson's disease: a cross-sectional study.

BACKGROUND: Malnutrition induced by swallowing difficulties (SD) impairs the quality of life and gives rise to SD-related costs in Parkinson's disease (PD) patients. With results of a swallowing difficulty questionnaire and data of resources specifically obtained such as SD-related costs, caregivers, and dietary therapies, this study is to suggest statistically supported ideas for improvements in arrangements for how participants cope with SD and maintain general well-being. METHODS: We interviewed 237 PD patients. The SD-related costs involved those incurred by the provision of dietary modifications, care oriented foods, alternatives, and supplements. Dietary therapies included rice porridge and commercially available care foods. The relationships between BMI (body mass index) and the severity of SD assumed in this paper as indicators for general well-being and as resources for coping with SD for PD patients were statistically analyzed. RESULTS: A lower BMI was found in participants eating porridge consistency rice (p = 0.003) and eating porridge rice is significantly related to the severity of SD (p < 0.0001) and PD (p = 0.002). The severity of SD increased with age and PD duration (p = 0.035, p = 0.0005). Outlays for dietary modifications are the lowest reported here (p < 0.004) but the number of participants using dietary modifications is the largest among the SD-related items (n = 58). Eating care foods were reported for 11 older participants (p < 0.0001), most female (10/11). No lower BMI was found in participants eating care foods when compared with participants eating ordinary foods. Dietary modifications were performed by caregivers (OR: 6.8, CI: 3.1-15.2, p < 0.0001) and were related to the presence of children (OR: 3.4, CI: 1.2-11.4. p = 0.024). Older participants commonly live with spouses and children. CONCLUSIONS: Severe SD is associated with higher costs of coping with SD. A lower BMI is associated with modified foods, mostly eaten to cope with SD. Presence of caregivers and other persons residing with the participants here are related to dietary modifications but not to care food-related costs. Care foods may be effective in preventing malnutrition although the number who are able to cover the added expenses is limited because of the higher prices and shortage of information on the usefulness of care foods.

Differentiation of speech in Parkinson's disease and spinocerebellar degeneration using deep neural networks.

INTRODUCTION: Assessing dysarthria features in patients with neurodegenerative diseases helps diagnose underlying pathologies. Although deep neural network (DNN) techniques have been widely adopted in various audio processing tasks, few studies have tested whether DNNs can help differentiate neurodegenerative diseases using patients' speech data. This study evaluated whether a DNN model using a transformer architecture could differentiate patients with Parkinson's disease (PD) from patients with spinocerebellar degeneration (SCD) using speech data. METHODS: Speech data were obtained from 251 and 101 patients with PD and SCD, respectively, while they read a passage. We fine-tuned a pre-trained DNN model using log-mel spectrograms generated from speech data. The DNN model was trained to predict whether the input spectrogram was generated from patients with PD or SCD. We used fivefold cross-validation to evaluate the predictive performance using the area under the receiver operating characteristic curve (AUC) and accuracy, sensitivity, and specificity. RESULTS: Average ± standard deviation of the AUC, accuracy, sensitivity, and specificity of the trained model for the fivefold cross-validation were 0.93 ± 0.04, 0.87 ± 0.03, 0.83 ± 0.05, and 0.89 ± 0.05, respectively. CONCLUSION: The DNN model can differentiate speech data of patients with PD from that of patients with SCD with relatively high accuracy and AUC. The proposed method can be used as a non-invasive, easy-to-perform screening method to differentiate PD from SCD using patient speech and is expected to be applied to telemedicine.

Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia.

The N-terminus of the PRNP gene normally contains a 5-octapeptide repeat (R1-R2-R2-R3-R4), and insertions at this locus can cause hereditary prion diseases. In the present study, we found a 5-octapeptide repeat insertion (5-OPRI) in a sibling case of frontotemporal dementia. Consistent with previous literature, 5-OPRI rarely met the diagnostic criteria for Creutzfeldt‒Jakob disease (CJD). We propose 5-OPRI as a suspected causative mutation for early-onset dementia, especially the frontotemporal type.

Long-term effects of the gait treatment using a wearable cyborg hybrid assistive limb in a patient with spinal and bulbar muscular atrophy: a case report with 5 years of follow-up.

Background: Spinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular degenerative disease characterized by the degeneration of lower motor neurons in the spinal cord and brainstem and neurogenic atrophy of the skeletal muscle. Although the short-term effectiveness of gait treatment using a wearable cyborg hybrid assistive limb (HAL) has been demonstrated for the rehabilitation of patients with SBMA, the long-term effects of this treatment are unclear. Thus, this study aimed to investigate the long-term effects of the continued gait treatment with HAL in a patient with SBMA. Results: A 68-year-old man with SBMA had lower limb muscle weakness and atrophy, gait asymmetry, and decreased walking endurance. The patient performed nine courses of HAL gait treatment (as one course three times per week for 3 weeks, totaling nine times) for ~5 years. The patient performed HAL gait treatment to improve gait symmetry and endurance. A physical therapist adjusted HAL based on the gait analysis and physical function of the patient. Outcome measurements, such as 2-min walking distance (2MWD), 10-meter walking test (maximal walking speed, step length, cadence, and gait symmetry), muscle strength, Revised Amyotrophic Lateral Sclerosis Functional Assessment Scale (ALSFRS-R), and patient-reported outcomes, were evaluated immediately before and after gait treatment with HAL for each course. 2MWD improved from 94 m to 101.8 m, and the ALSFRS-R gait items remained unchanged (score 3) for approximately 5 years. The patient could maintain walking ability in terms of gait symmetry, walking endurance, and independence walking despite disease progression during HAL treatment. Conclusion: The long-term gait treatment with HAL in a patient with SBMA may contribute to the maintenance and improvement of the gait endurance and ability to perform activities of daily living. The cybernics treatment using HAL may enable patients to relearn correct gait movements. The gait analysis and physical function assessment by a physical therapist might be important to maximize the benefits of HAL treatment.

Prospective 10-year surveillance of human prion diseases in Japan.

We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.

Executive dysfunction in patients with spinocerebellar ataxia type 3.

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex-ventral dentate nucleus-thalamus-prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.

Cognitive dysfunction in patients with spinocerebellar ataxia type 6.

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 6 (SCA6). We examined 13 patients with genetically confirmed SCA6 and 13 healthy control subjects matched for age, years of education, global cognitive status, and intellectual ability. We administered verbal memory (word recall and word recognition), executive function (digit span, category and letter fluency, Frontal Assessment Battery, and Trail Making Test-A and B), and visuospatial construction (figure copying) tests. We found that the patients with SCA6 had significantly lower scores on the demanding word recall and letter fluency tests compared to the control subjects, while word recognition was well preserved in the patients with SCA6. The other executive functions tested, as well as visuospatial construction, were preserved in the SCA6 group. However, although memory encoding and storage processes were preserved, the retrieval of memorized information concerning frontal function might be selectively affected in patients with SCA6 compared to in control subjects. The impaired word recall and letter fluency noted in patients with SCA6 were interpreted as being related to a word-retrieval disability. Such dysfunctions may be attributed to damage in the frontal-cerebellum circuit owing to SCA6.

Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA).

ABSTRACT We clinically and genetically studied three patients in a family with dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG repeat alleles of the DRPLA gene (normal < or = 34 repeats). Cerebellar ataxia first developed in the 6-7th decades and was the predominant feature for more than 10 years in all three, after which two of them manifested dementia and choreiform movements in the advanced stage. Atrophy of the cerebellum and brain stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based on the clinical findings alone. Our experience implies that DRPLA must be taken into account in the differential diagnosis of late onset ataxic disorders, since it can easily be overlooked.

[Validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis--assessment questionnaire 40 (ALSAQ-40)].

We studied validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis (ALS) assessment questionnaire 40 (ALSAQ-40). The original version contains forty questions measuring five areas (domains) of health status: Physical Mobility, ADL/Independence, Eating and Drinking, Communication and Emotional Functioning. Data were obtained from 39 ALS patients and from their physicians at 15 centers in Japan. Patients completed the ALSAQ-40 and the SF-36, and provided information on their age and their status of ventilator use. Their physicians provided information on the date of diagnosis, type of disease and clinical characteristics, and ALSFRS-R. The patients' average age was 58.5 years, and 64% were men. The mean duration since diagnosis was 39.1 months. Forty four percent were classical ALS patients and 46% were receiving a respiratory intervention. Although there was much heterogeneity, the scores for Physical Mobility and ADL/Independence were higher(indicating worse health status)than the scores for the other domains. Item-scale correlations were strong, except for the item "felt embarrassed in social situations" in the Emotional Functioning domain. All the domains had very high internal consistency: Cronbach's alphas ranged 0.95 to 0.97. With regard to the cluster structure of the forty items, the Eating and Drinking domain and the Communication clustered together. The reason might be that the former consisted of only three items and both domains measure bulbar symptoms. Domain scores correlated significantly with scores of related dimensions in the SF-36 and ALSFRS-R, and did not correlate strongly with unrelated domains. The five items of the ALSAQ-5 correlated with all five domain scores on the ALSAQ-40. These results should be interpreted with caution because we analyzed together data from ALS patients with various characteristics. In conclusion, although we may need to add and remove some items and modify the wording of others, the Japanese version of the ALSAQ-40 had high validity and is likely to be useful in evaluating of QOL in ALS patients. Whether the ALSAQ-5 can be used in place of the ALSAQ-40 is a matter for further study.

[Effects of low-dose pergolide therapy on cardiac valves in patients with Parkinson's disease].

BACKGROUND: Pergolide mesilate is widely used to treat Parkinson's disease in both the USA and Japan, but the maintenance dose is distinctly different between the USA (usually more than 1.5 mg/day) and Japan (usually less than 1.5 mg/day). Although several reports from the USA have suggested that mitral, aortic, and tricuspid valvular lesions were caused by pergolide, it is unclear whether low-dose pergolide therapy causes such valvular lesions. OBJECTIVES: The effects of low-dose pergolide therapy on cardiac valves were studied in Japanese patients with Parkinson's disease. METHODS: One hundred and five consecutive patients with Parkinson's disease approved for our protocol were enrolled in this study. Forty patients were treated with low-dose pergolide (0.05-1.5 mg/day for 2-115 months), and were included in the pergolide group (mean age 71 +/- 6 years). The other 44 patients received no ergot-derived dopamine receptor agonists, and 32 patients acted as age-matched controls (mean age 71 +/- 7 years). Both groups of patients underwent echocardiographic examination to detect organic lesions in cardiac valves such as thickening of the leaflet, annular calcification, restriction of valve motion and valvular tenting, and valvular regurgitation greater than 2 + on the 4-point scale. RESULTS: No significant difference was observed in the incidence of aortic, mitral and pulmonic valve lesions between the pergolide group and the control group. Although no organic lesions were detected in the tricuspid valve, the incidence of tricuspid regurgitation was significantly higher in the pergolide group than in the control group (p < 0.05). CONCLUSIONS: Although low-dose pergolide of less than 1.5 mg/day does not cause serious damage in the left-sided valves, it may induce tricuspid regurgitation.