T Stijnen

Publications (3)19.04 Total impact

• Article: Treatment effect modifiers for the patient education programme for Parkinson's disease.

  L E I A'Campo, E M Wekking, N G A Spliethoff-Kamminga, T Stijnen, R A C Roos
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  ABSTRACT: A recent randomised controlled trial showed significant benefits for Parkinson's disease (PD) caregivers' psychosocial problems and need for help and a trend towards significant improvement of patients' quality of life after participation in the Patient Education Programme for Parkinson's disease (PEPP). Large variations in change scores were found, indicating variation in benefit. The aim of this study was to search for treatment effect modifiers. Outcome measures were patients' quality of life [Parkinson's Disease Questionnaire (PDQ)-39] and caregivers' psychosocial burden [Belastungsfragebogen Parkinson Angehörigen kurzversion (BELA-A-k)]. Candidate treatment effect modifiers were participants' characteristics and baseline scores on psychological questionnaires (BELA-P/A-k, PDQ-39, EQ-5D, Self-rating Depression Scale) and patients' neuropsychological test scores (Mini Mental State Examination, National Adult Reading Test, Dutch version, Word Test, Behavioural Assessment of the Dysexecutive Syndrome rule shift, Trail Making Test, Stroop). Secondary analyses of data from a randomised controlled trial with 64 patients and 46 caregivers were performed using regression analyses with treatment group interaction terms. No significant modifiers were found for the patients. In the caregiver group, a higher MMSE score of the patient at baseline was found to be a significant predictor of a lower BELA-A-k Bothered by score post-intervention of the caregiver. A potential predictor of treatment benefit was found for caregivers of PD patients with better cognitive functioning. This study did not find treatment effect modifiers for PD patients: demographics, disease stage and time of diagnosis, cognitive functioning, level of baseline psychosocial burden, participating with or without a caregiver, and caregiver changes did not influence treatment outcome. The PEPP seems suitable for the majority of patients.
  International Journal of Clinical Practice 01/2012; 66(1):77-83. · 2.41 Impact Factor
• Article: Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease.

  N A Aziz, C K Jurgens, G B Landwehrmeyer, W M C van Roon-Mom, G J B van Ommen, T Stijnen, R A C Roos
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  ABSTRACT: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. Using linear regression and mixed-effects models, the influence of mutant and normal CAG repeat sizes interaction was assessed on 1) age at onset in 921 patients with HD, 2) clinical severity and progression in 512 of these patients with follow-up data available, and 3) basal ganglia volume on magnetic resonance images in 16 premanifest HD mutation carriers. Normal and mutant CAG repeat sizes interacted to influence 1) age at onset (p = 0.001), 2) severity or progression of motor, cognitive, and functional, but not behavioral, symptoms in patients with HD (all p < 0.05), and 3) in premanifest subjects, basal ganglia volumes (p < 0.05). In subjects with mutant CAG expansions in the low range, increasing size of the normal repeat correlated with more severe symptoms and pathology, whereas for those subjects with expansions in the high range, increasing size of the normal repeat correlated with less severe symptoms and pathology. Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal and mutant huntingtin (fragments) and needs further elucidation. These findings may have predictive value and are essential for the design and interpretation of future therapeutic trials.
  Neurology 09/2009; 73(16):1280-5. · 8.31 Impact Factor
• Article: Weight loss in Huntington disease increases with higher CAG repeat number.

  N A Aziz, J M M van der Burg, G B Landwehrmeyer, P Brundin, T Stijnen, R A C Roos
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  ABSTRACT: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.
  Neurology 11/2008; 71(19):1506-13. · 8.31 Impact Factor