Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan.

Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders.

Impact of Residual Drug in the Pharynx on the Delayed-On Phenomenon in Parkinson's Disease Patients.

BACKGROUND AND OBJECTIVE: The delayed-on phenomenon (DOP) related to levodopa treatment frequently disturbs quality of life in advanced-stage Parkinson's disease (PD) patients. The objective of this study was to explore the impact of swallowing dysfunction on the development of DOP. METHODS: Swallowing function was investigated by endoscopic evaluation in 11 PD patients with the DOP and 9 PD patients without the DOP during the on phase. Residual drug in the pharynx after taking the drug in tablet, capsule, and powder forms was also observed. RESULTS: Residual drug was seen in the pharynx in six cases (30.0%). Pooling of saliva, delayed swallowing reflex, and residual drug were more frequent in the DOP group than in the group without the DOP (P < 0.05). The odds ratios for residual drug in the pharynx, pooling of saliva, and delayed swallowing reflex for the DOP were 42.7 (95% confidence interval, 1.89-962.9), 14.0 (95% confidence interval, 1.25-156.6), and 15.8 (95% confidence interval, 1.75-141.4), respectively. CONCLUSIONS: These results suggest that swallowing dysfunction leading to residual antiparkinsonian drug in the pharynx has substantial impacts on the DOP in PD patients.

Serum uric acid level is linked to the disease progression rate in male patients with multiple system atrophy.

OBJECTIVES: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder that may be caused in part by oxidative stress. Uric acid (UA) protects neurons in neurodegenerative disorders via antioxidative effects. The aim of this study was to investigate the relationship between the serum UA concentration and disease progression in MSA patients. PATIENTS AND METHODS: A total of 53 Japanese MSA patients were enrolled in this study. The disease progression rate was estimated by the rate of global disability scale change per year. The relationship between the serum UA concentration and disease progression was assessed by Spearman's correlation analysis. Disease progression depending on the UA concentration was also estimated by multivariate logistic regression analysis. RESULTS: MSA patients with the highest serum UA concentration had lower disease progression rates than those with the lowest concentration. Spearman's correlation analysis showed an inverse correlation between the serum UA concentration and disease progression in male patients. Multivariate logistic regression analysis confirmed that the UA concentration was independently related to disease progression only in male patients. CONCLUSION: These results suggest that serum UA may be associated with disease progression in male patients with MSA.

Utility of the Japanese version of the 9-item Wearing-off Questionnaire.

BACKGROUND AND PURPOSE: The 9-item Wearing-off Questionnaire (WOQ-9) is a useful tool for screening of wearing-off. We performed a validation study of the Japanese version of the WOQ-9 (JWOQ-9) using a cross-sectional design in Japanese Parkinson's disease (PD) patients diagnosed with sporadic PD and treated with levodopa. METHODS: Subjects with severe dementia, uncontrolled psychiatric comorbidities, and previous PD neurosurgery were excluded. The wearing-off phenomenon was detected according to the JWOQ-9, and the results were compared with independent evaluations of wearing-off conducted by PD specialists blinded to the JWOQ-9 results. To validate the JWOQ-9, a sample size of at least 70 patients with wearing-off and 70 patients without wearing-off was required. Therefore, a total of 180 patients (101 patients with wearing-off and 79 patients without wearing-off) were enrolled. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the JWOQ-9 were 94.1%, 39.2%, 66.4%, and 83.8%, respectively. Motor symptom questions demonstrated both moderate sensitivity (58.1-87.3%) and specificity (60.4-87.5%). In contrast, non-motor symptom questions demonstrated fair to moderate sensitivity (51.5-64.6%), with high specificity (80.0-94.1%). Like the original WOQ-9, the JWOQ-9 exhibits significant value for detecting possible wearing-off. CONCLUSIONS: The JWOQ-9 is a useful screening tool for detecting wearing-off of both motor and non-motor symptoms.