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Aim To investigate the characteristics and severity of dysarthria in children and adults with ataxia telangiectasia. Method All children and adults with ataxia telangiectasia who visited our multidisciplinary outpatient clinic for ataxia telangiectasia were asked to participate in this study, which took place in March 2019. To evaluate dysarthria, we used the Radboud Dysarthria Assessment in adults (older than 18y) and the paediatric Radboud Dysarthria Assessment in children (5–18y), including the observational tasks ‘conversation’ and ‘reading’, and the speech‐related maximum performance tasks ‘repetition rate’, ‘phonation time’, ‘fundamental frequency range’, and ‘phonation volume’. Speech intelligibility was measured using the Intelligibility in Context Scale. Results Twenty‐two individuals (15 children [5–17y], seven adults [19–47y]; 14 males and eight females; mean age 19y, SD 15y 2mo) participated. Dysarthria was present in all participants and characterized by ataxic components in adults and similar uncontrolled movements in children. In most participants, speech was mildly to mildly/severely affected. Almost all participants had an abnormal score for at least one maximum performance task. Interpretation Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements, resulting in monotonous, unstable, slow, hypernasal, and chanted speech. What this paper adds Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements.Dysarthria in ataxia telangiectasia results in monotonous, unstable, slow, hypernasal, and chanted speech.Dysarthria in ataxia telangiectasia can be assessed using the Radboud Dysarthria Assessment and the paediatric Radboud Dysarthria Assessment., What this paper adds Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements.Dysarthria in ataxia telangiectasia results in monotonous, unstable, slow, hypernasal, and chanted speech.Dysarthria in ataxia telangiectasia can be assessed using the Radboud Dysarthria Assessment and the paediatric Radboud Dysarthria Assessment.

Contains fulltext : 244271.pdf (Publisher’s version ) (Open Access) BACKGROUND: Treatment of animal models with ataxia telangiectasia (A-T) with nicotinamide riboside (NR) improved their neurological outcome and survival. OBJECTIVE: The aim of this study is to investigate the effects of NR in patients with A-T. METHODS: In this open-label, proof-of-concept study, 24 patients with A-T were treated with NR during four consecutive months. The effects of NR on ataxia, dysarthria, quality of life, and laboratory parameters were analyzed. RESULTS: During treatment, ataxia scores improved; mean total Scale for the Assessment and Rating of Ataxia and International Cooperative Ataxia Rating Scale scores decreased to 2.4 and 10.1 points, respectively. After NR withdrawal, ataxia scores worsened. In immunodeficient patients, the mean serum IgG concentration increased substantially until the end of the study period with 0.52 g/L. Untargeted metabolomics analysis revealed increased plasma levels of NR metabolites and purine nucleosides during treatment. Adverse effects did not occur. CONCLUSIONS: Treatment with NR is tolerated well and associated with improvement in ataxia and serum immunoglobulin concentrations in patients with A-T. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Aim Neurofilament light chain (NfL) is recognized as a blood biomarker in several neurodegenerative disorders, but its possible relevance in Ataxia Telangiectasia (A-T) has not been examined. The aim of this study was to investigate the biomarker potential of blood NfL concentrations in patients with A-T. Method Blood (serum/plasma) NfL concentrations were measured in a Dutch and an American cohort of patients with A-T and compared to control values. Additionally, correlations between NfL concentrations and disease phenotype (classic versus variant A-T) were studied. Results In total 40 (23 Dutch and 17 American) patients with A-T (32 patients with classic A-T and 7 patients with variant A-T) and 17 age- and gender-matched (to the American cohort) healthy controls were included in this study. Blood (serum/plasma) NfL concentrations in patients with classic A-T and age ≤ 12 years were elevated compared to age matched controls. Patients with classic A-T > 12 years also had higher blood (serum/plasma) NfL concentrations (here: compared to age-dependent reference values found in the literature). Patients with classic A-T had higher blood (serum/plasma) NfL concentrations than patients with the variant phenotype. Conclusion Blood (serum/plasma) NfL concentrations are elevated in patients with classic A-T and appear to correlate with the disease phenotype (classic versus variant). Therefore, blood (serum/plasma) NfL may be a promising biomarker in A-T.

The goal of metabolomics is to measure as many metabolites as possible in order to capture biomarkers that may indicate disease mechanisms. Variable selection in chemometric methods can be divided into the following two groups: (1) sparse methods that find the minimal set of variables to discriminate between groups and (2) methods that find all variables important for discrimination. Such important variables can be summarized into metabolic pathways using pathway analysis tools like Mummichog. As a test case, we studied the metabolic effects of treatment with nicotinamide riboside, a form of vitamin B3, in a cohort of patients with ataxia&ndash, telangiectasia. Vitamin B3 is an important co-factor for many enzymatic reactions in the human body. Thus, the variable selection method was expected to find vitamin B3 metabolites and also other secondary metabolic changes during treatment. However, sparse methods did not select any vitamin B3 metabolites despite the fact that these metabolites showed a large difference when comparing intensity before and during treatment. Univariate analysis or significance multivariate correlation (sMC) in combination with pathway analysis using Mummichog were able to select vitamin B3 metabolites. Moreover, sMC analysis found additional metabolites. Therefore, in our comparative study, sMC displayed the best performance for selection of relevant variables.

Long-term health-related quality of life (HRQOL) in the elderly after percutaneous coronary intervention (PCI) is unknown. We 1) compared HRQOL of elderly (≥70 years) with younger patients (70 years) at 6, 12, 36 months post-PCI, and 2) examined whether predictors of impaired HRQOL 36 months post-PCI differed between older and younger patients.A prospective cohort of 651 PCI patients (26.3% ≥70 years) completed the SF-36 at 6, 12 and 36 months post-PCI. Older patients experienced a poorer physical HRQOL at all time points and worse mental HRQOL with respect to vitality and role emotional functioning (all p-values0.05). By 36 months, the HRQOL for the older patients worsened in five of the eight subdomains (all p-values0.05). Younger patients did not experience enduring changes in HRQOL, with the exception of role physical functioning. Predictors of impaired HRQOL were generally different for the elderly (diabetes, previous PCI) compared to younger cohorts (smoking, previous bypass surgery, ACE inhibitors), although poor six-month HRQOL, anxiety and depression were common predictors for both groups.Elderly PCI patients experience a deteriorating and poorer HRQOL than younger patients across three years. Contrary to younger patients, three-year HRQOL of elderly patients is irrespective of adverse events during outcomes.