Defining Speech Subtypes in De Novo Parkinson Disease: Response to Long-term Levodopa Therapy

Background and Objectives:Patterns of speech disorder in Parkinson's disease (PD), that are highly variable across individual patients, were not systematically studied. Our aim was to identify speech subtypes in treatment-naïve PD patients and examine their response to long-term dopaminergic therapy.Methods:We recorded speech data from a total of 111 de-novo PD participants; 83 of the participants completed the 12-month follow-up (69 PD subjects on stable dopaminergic medication and 14 untreated PD controls). Unsupervised k-means cluster analysis was performed on eight distinctive parameters of hypokinetic dysarthria examined using quantitative acoustic analysis.Results:Three distinct speech subtypes with similar prevalence, symptom duration and motor severity were detected: 'prosodic', 'phonatory-prosodic' and 'articulatory-prosodic'. Beside monopitch and monoloudness that were common in each subtype, speech impairment was more severe in phonatory-prosodic subtype with predominant dysphonia and articulatory-prosodic subtype with predominant imprecise consonant articulation than in prosodic subtype. Clinically, the prosodic subtype was characterized by a prevalence of women and younger age while articulatory-prosodic subtype by the prevalence of men, older age, greater severity of axial gait symptoms and poorer cognitive performance. Phonatory-prosodic subtype clinically represented intermediate status in age with mostly men and preserved cognitive performance. While speech of untreated PD controls deteriorated over one year (p = 0.02), long-term dopaminergic medication maintained stable speech impairment severity in prosodic and articulatory-prosodic subtypes and improved speech performance in patients with phonatory-prosodic subtype (p = 0.002).Discussion:Distinct speech phenotypes in de-novo PD reflect divergent underlying mechanisms and allow to predict response of speech impairment to levodopa therapy.Classification of Evidence:This study provides Class II evidence that, in patients with newly diagnosed PD with speech impairment, speech phenotype is associated with levodopa responsiveness.

Very-Low-Dose Levodopa Therapy for Pediatric Neurological Disorders: A Preliminary Questionnaire in Japan

Introduction: Post-synaptic dopamine receptor supersensitivity (DARSS) has been extensively researched by Dr. Masaya Segawa, who has investigated the efficacy of very-low-dose levodopa therapy (VLDT; 0.5–1 mg/kg/day). Considerable Japanese research supports the possibility that VLDT could be used to treat pediatric neurological disorders. We conducted an on-line survey in 2014 to collect real-world data on the use of VLDT to treat DARSS.Methods: A two-step survey, including a screening test and questionnaire, was posted on a private internet site that could be accessed via the VLDT Research Group home page, and 1,165 pediatric neurologists across Japan were invited to complete it.Results: A total of 25 respondents reported prescribing VLDT; 19 used VLDT to treat autism spectrum disorder, 14 for tics, 12 for speech delay, 9 for Rett syndrome, 7 for attention-deficit/hyperactivity disorder, intellectual disability, and 6 for sleep problems. Twelve respondents reported prescribing a dose of 0.5 mg/kg. Twenty-two reported that VLDT was effective for treating behavioral problems, and twenty reported a good efficacy for treating motor symptoms. Adverse events had a low incidence. Notably, respondents chose VLDT for its possible action in DARSS and for its safety. VLDT was commonly used for behavioral problems in patients younger than 5 years, and for motor symptoms in aged 5–9 years.Conclusion: VLDT could safely treat behavioral and motor symptoms in pediatric neurological disorders. In contrast, dopamine antagonists are associated with potent efficacy, but with adverse effects such as sleepiness and obesity. Further surveys should be conducted with a broader participants.

Analysis of Motor Complication and Relative Factors in a Cohort of Chinese Patients with Parkinson’s Disease

Objective. Motor complications are common in Parkinson’s disease (PD). The reported occurrence of motor complications varies across regions and races. The aim of our study was to describe the development of dyskinesias and motor fluctuations among Chinese PD patients and the relative risk factors. Methods. In the current cross-sectional survey study, PD patients with motor fluctuations and dyskinesia were enrolled from March to November 2018 in Shaanxi province, a northwest area of China. Data were collected by the movement disorder specialists. A self-designed questionnaire was utilized during face-to-face interviews. In addition, the relevant factors of motor complications were analyzed by univariable and multivariable analyses. Results. Of the166 PD patients recruited, 52 (31.33%) and 25 (15.06%) patients had motor fluctuations and dyskinesia, respectively, which occurred in 6.76 ± 3.77 and 8.61 ± 4.46 years after the onset of motor symptoms and 5.37 ± 3.33 and 6.80 ± 3.43 years after the treatment of levodopa therapy, respectively. Patients with motor fluctuations and dyskinesias had longer disease duration, younger onset age, higher Hoehn–Yahr stages and UPDRS III scores, higher daily levodopa dosage and levodopa equivalent daily dose (LEDD), and longer duration of levodopa treatment (P<0.05). Bradykinesia-rigidity dominant patients had higher incidences of motor fluctuations (61.54% vs 38.46%) and dyskinesias (68.00% vs 32.00%) than tremor-dominant patients (P<0.05). Results of the multivariate logistic regression analyses showed that the duration of levodopa therapy, age of the onset, and bradykinesia-rigidity dominant type were independent risk factors of motor fluctuations (P<0.05). In addition, duration of disease and bradykinesia-rigidity dominant type were independent risk factors of dyskinesia (P<0.05). Conclusions. The rate of motor fluctuations was higher than dyskinesias in Chinese patients with Parkinson’s disease. Patients with younger age onset, bradykinesia-rigidity dominant type, longer disease duration, and longer duration of levodopa therapy are more likely to develop motor complications.