Search

Purpose: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese., Method: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls)., Results: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative., Conclusions: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1,587 cases. Mutations were found in 14.1% of patients; 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians, whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations. ANN NEUROL 2020;88:843-850., (© 2020 American Neurological Association.)

LRRK2, SNCA , and VPS35 are unequivocally associated with autosomal dominant Parkinson's disease (PD). We evaluated the prevalence of LRRK2, SNCA , and VPS35 mutations and associated clinical features in a large French multi-center cohort of PD patients. Demographic and clinical data were collected for 1,805 index cases (592 with autosomal dominant inheritance and 1,213 isolated cases) since 1990. All probands were screened with TaqMan assays for LRRK2 Gly2019Ser. In the absence of this mutation, the coding sequences of the three genes were analyzed by Sanger sequencing and/or next-generation sequencing. The data for the three genes were analyzed according to age at onset, family history, ethnic origin and clinical features. We identified 160 index cases (8.9%) with known pathogenic variants: 138 with pathogenic LRRK2 variants (7.6%), including 136 with the Gly2019Ser mutation, 19 with SNCA point mutations or genomic rearrangements (1.1%), and three with the VPS35 Asp620Asn mutation (0.16%). Mutation frequencies were higher in familial than isolated cases, consistent with autosomal dominant inheritance (12.0 vs. 7.3%; OR 1.7, 95% CI [1.2-2.4], p = 0.001). PD patients with LRRK2 variants were more likely to have higher rates of late-onset PD (>50 years; OR 1.5, 95% CI [1.0-2.1], p = 0.03), whereas those with SNCA mutations tended to have earlier age at onset disease (≤ 50 years, p = 0.06). The clinical features of LRRK2 carriers and those without any pathogenic variants in known PD-associated genes were similar. The likelihood of detecting disease-causing mutations was higher in cases compatible with autosomal dominant inheritance., (Copyright © 2020 Lesage, Houot, Mangone, Tesson, Bertrand, Forlani, Anheim, Brefel-Courbon, Broussolle, Thobois, Damier, Durif, Roze, Tison, Grabli, Ory-Magne, Degos, Viallet, Cormier-Dequaire, Ouvrard-Hernandez, Vidailhet, Lohmann, Singleton, Corvol and Brice.)

Theory of Mind refers to the ability to infer other’s mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person’s beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.

This preliminary study aimed to adapt the Dysarthria Impact Profile (DIP) in French and to confirm its relevance for the assessment of the psychosocial impact of dysarthria in Parkinson's disease (PD). The DIP scale was administered to 10 people with PD and 10 age-matched control subjects. The DIP psychometric properties were calculated (discriminant validity, internal consistency, and concurrent validity), notably by using the Voice Handicap Index (VHI) for interscale comparisons. The French version of the DIP discriminated people with PD from control subjects (χ (2) test, P < 0.05). Good internal consistency was observed in both populations (Cronbach's α = 0.93 for PD people and α = 0.76 for control subjects). The DIP was highly correlated with the VHI (Spearman's ρ = -0.70, P < 0.01), confirming the external validity of the scale. There was no direct relationship between PD speech and quality of life as assessed by the Parkinson's Disease Questionnaire-39 (PDQ-39). Our preliminary data suggest that the French version of the DIP has the potential to make a useful contribution for the assessment and outcome management in acquired dysarthria for both clinicians and researchers.

Objective: Rasagiline is a second-generation, irreversible MAO-B inhibitor (MAOB-I) previously shown to be efficacious and well-tolerated compared to placebo in the treatment of early Parkinson's disease (PD). ACTOR (ACceptabilité TOlérance Rasagiline) was a 15-week, multi-center, randomized, double-blind study aimed to assess the safety and tolerability of rasagiline compared to the dopaminergic agonist pramipexole in the treatment of early PD., Methods: Patients with early, untreated idiopathic PD were randomized to receive 1 mg rasagiline (n = 53) or 1.5 mg pramipexole (n = 56) daily. The primary outcome was the number of patients experiencing a 'clinically important adverse event' (classified as a serious adverse event, an event leading to withdrawal or severe according to the patient). Safety outcomes were evaluated by the investigator and the patient. Analysis of the primary criterion was a comparative analysis using the chi-squared test. The Wilcoxon Mann-Whitney test was conducted to test the severity of patient-reported adverse events. Other tests performed include a covariance analysis and Student's t-tests., Results: Mean disease duration was 3.4 months, and mean age was 62.6 years. Of patients taking pramipexole, 44.6% reported at least one 'clinically important' adverse event compared to 32.1% of patients taking rasagiline; non-inferiority of rasagiline was reached, with a difference in proportions of -12.6% [confidence interval of -27.8%; 2.6%]. There were no significant differences in clinical effectiveness between the treatments, measured by clinical and patient global impression of improvement (CGI-I, PGI-I) and PDQ-8 scales. A significant decrease in the incidence of gastrointestinal symptoms (p = 0.015) and sleep disorders (p = 0.027) was reported by physicians in the rasagiline group compared to the pramipexole group; the propensity to sleepiness improved significantly in the rasagiline group (p = 0.020), and worsened in the pramipexole group (p = 0.042)., Limitations: Limitations of this study include the limited sample size due to the lower than anticipated recruitment and the accidental inclusion of a patient who had taken contraindicated medication., Conclusions: In this study, the safety profile of rasagiline had clinically favorable differences in gastrointestinal and sleep adverse events compared to pramipexole, whilst showing comparable clinician and patient-rated clinical effectiveness as a monotherapy for the treatment of early idiopathic PD.

Mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene, encoding a component of the eIF4F translation initiation complex, were recently reported as a possible cause for the autosomal dominant form of Parkinson's disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a series of 251 index cases with autosomal dominant PD, mostly of French origin and in 236 European control subjects. We identified 12 rare coding variants (either nonsynonymous amino acid substitutions or in frame deletions/insertions), including 6 variants present only in cases and 3 in controls. Segregation was possible only for 1 variant (p.E462delInsGK) that was found in 2 affected siblings. In addition, we found 2 previously reported pathogenic variants in 2 isolated patients (p.G686C) and in a control subject (p.R1197W). These data do not support the pathogenicity of several EIF4G1 variants in PD, at least in the French population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Ergot alkaloids, such as ergotamine, have been associated with numerous vascular complications and with valvular heart disease. The authors describe a man who developed fibrosis of three heart valves during a 5-year treatment with bromocriptine for Parkinson disease. There were no other plausible causes. To our knowledge, such a side effect has never been described with this drug.