Gait and postural disorders in parkinsonism: a clinical approach

Contains fulltext : 229737.pdf (Publisher’s version ) (Open Access)Disturbances of balance, gait and posture are a hallmark of parkinsonian syndromes. Recognition of these axial features can provide important and often early clues to the nature of the underlying disorder, and, therefore, help to disentangle Parkinson's disease from vascular parkinsonism and various forms of atypical parkinsonism, including multiple system atrophy, progressive supranuclear palsy, and corticobasal syndrome. Careful assessment of axial features is also essential for initiating appropriate treatment strategies and for documenting the outcome of such interventions. In this article, we provide an overview of balance, gait and postural impairment in parkinsonian disorders, focusing on differential diagnostic aspects

Towards seeing the visual impairments in Parkinson's disease: protocol for a multicentre observational, cross-sectional study

Contains fulltext : 205535.pdf (publisher's version ) (Open Access)BACKGROUND: Visual disorders are common in Parkinson's disease (PD) but their exact frequency and severity are unknown. Good visual functioning is crucial for patients with PD, because of their need to compensate for loss of automated motor control and their postural instability, forcing patients to guide their movements visually. Here, we describe the study design of a cross-sectional, multi-centre study aiming to: (1) validate the Visual Impairment screening questionnaire (VIPD-Q, which aims to identify PD patients who should be referred to an ophthalmologist for further assessment); (2) study the prevalence of visual disorders in PD; (3) study the severity and clinical impact of different types of visual disorders in PD; and (4) explore treatment options for ophthalmologic disorders in PD, as a basis for future guideline development. METHODS: This study consists of two phases. In phase one, 750 PD patients and 250 healthy controls will be recruited to complete the VIPD-Q. In phase two, a subgroup of responders (n = 100) (with the highest and lowest scores on the VIPD-Q) will be invited for an extensive neurological and ophthalmological assessment. The in-depth ophthalmologic examination will serve as the "gold standard" for validating the VIPD-Q. Moreover, these assessments will be used to study associations between visual disorders and clinical presentation, in order to gain more insight in their clinical impact. DISCUSSION: Our study will heighten the awareness of visual problems in PD and offers a robust starting point to systematically approach this subject. In current daily practice, the association between visual problems and PD is far from obvious to both patients and clinicians. Consequently, patients may not adequately report visual problems themselves, while clinicians miss potentially treatable visual disorders. Routinely asking patients to complete a simple screening questionnaire could be an easy solution leading to timely identification of visual problems, tailored treatment, restored mobility, greater independence and improved quality of life. TRIAL REGISTRATION: Dutch Trial Registration, NL7421 , Registered on 4 December 2018 - Retrospectively registered

Undetected ophthalmological disorders in Parkinson's disease

BACKGROUND: Ophthalmological disorders are common and frequently disabling for people with Parkinson's disease (PD). However, details on the prevalence, severity and impact of ophthalmological disorders thus far lacking. We aimed to identify PD patients with undetected ophthalmological disorders in a large cross-sectional, observational study. METHODS: We previously delivered a screening questionnaire to detect ophthalmological symptoms (Visual impairment in PD questionnaire; VIPD-Q) to 848 patients. Here, we report on a subgroup of 102 patients who received complete ophthalmological assessment aimed at identifying clinically relevant ophthalmological diseases, which were classified as either vison-threatening or not. Impact on daily life functioning was measured using the visual functioning-25 questionnaire (VFQ-25) and fall frequency. RESULTS: Almost all patients (92%) had one or more clinically relevant ophthalmological disorders. Of those, 77% had a potentially vision-threatening disease, while 34% had a potentially treatable ophthalmological disease which impacted on quality of life. The most prevalent ophthalmological disorders were dry eyes (86%), ocular misalignment (50%) and convergence insufficiency (41%). We found a weak but significant association between clinically relevant ophthalmological diseases and both fall frequency (R(2) = 0.15, p = 0.037) and VFQ-25 score (R(2) = 0.15, p = 0.02). The VIPD-Q could not correctly identify patients with relevant ophthalmological disorders. CONCLUSIONS: Surprisingly, in our study sample, many participants manifested previously undetected ophthalmological diseases, most of which threatened vision, impacted on daily life functioning and were amenable to treatment. Screening for these ophthalmological disorders using a questionnaire asking about symptoms seems insufficient. Instead, episodic ophthalmological assessments should be considered for PD patients, aiming to identify vision-threatening yet treatable diseases. TRIAL REGISTRATION: Dutch Trial Registration, NL7421

Tit for tat

$\bf Objective:$ We aimed to investigate costly punishment in patients with Huntington’s disease (HD). $\bf Background:$ HD is an autosomal dominant neurodegenerative disease with motor, cognitive, and psychiatric symptoms. As neuropsychiatric abnormalities often precede motor symptoms, we wanted to assess whether costly punishment is part of the neuropsychological profile of patients with HD. $\bf Methods:$ A total of 40 non-demented subjects were prospectively enrolled in this study with a between-subject design comparing manifest HD patients ($\it n$ = 18) to healthy controls (HC; (\it n\) = 22). All participants performed 8 rounds of a costly punishment task, in which money was shared unevenly in 5 rounds or in a fair manner in the remaining 3 rounds. Participants then had to decide whether they wanted to punish the trustee. Furthermore, all participants underwent neuropsychological background tasks. $\bf Results:$ HD patients performed worse in the neuropsychological background tests compared to HC (all (\it p\) values <0.05). Moreover, HD patients punished more often in fair (Wald $\chi^{2}$ = 5.03, (\it p\) = 0.025) but not in unfair rounds (Wald $\chi^{2}$ = 1.63, (\it p\) = 0.202). $\bf Conclusions:$ Our results demonstrate increased costly punishment during fair conditions in HD patients. Whether this behaviour is due to a lack of recognition of social norms, an impairment in top-down inhibition, or an effect of antidopaminergic medication remains unclear

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA) : Rationale, Design, and Baseline Data

Altres ajuts: F. Hoffmann-La Roche Ltd.Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149