Background: Movement Disorder Society-Unified Parkinson's Rating Scale Part III (MDS-UPDRS III) is the gold standard for assessing medication effects in patients with Parkinson's disease (PD).... Show moreBackground: Movement Disorder Society-Unified Parkinson's Rating Scale Part III (MDS-UPDRS III) is the gold standard for assessing medication effects in patients with Parkinson's disease (PD). However, short and rater-independent measurements would be ideal for future trials. Objectives: To assess the ability of 3 different finger tapping tasks to detect levodopa/carbidopa-induced changes over time and to determine their correlation and compare their discriminatory power with MDS-UPDRS III. Methods: This was a randomized, double-blind, crossover study in 20 patients with PD receiving levodopa/carbidopa and placebo capsules after overnight medication withdrawal. Pre- and up to 3.5 hours postdose, MDS-UPDRS III and tapping tasks were performed. Tasks included 2 touchscreen-based alternate finger tapping tasks (index finger versus index-middle finger tapping) and a thumb-index finger task using a goniometer. Results: In the alternate index finger tapping task, levodopa/carbidopa compared with placebo resulted in significantly faster (total taps: 12.5 [95% confidence interval, CI, 6.7-18.2]) and less accurate tapping (total spatial error: 240 mm [95% CI, 123-357 mm]) with improved rhythm (intertap interval standard deviation [SD], -16.3% [95% CI, -29.9% to 0.0%]). In the thumb-index finger task, tapping was significantly faster (mean opening velocity, 151 degree/s [64-237 degree/s]), with a higher mean amplitude (8.4 degrees [3.7-13.0 degrees]) and improved rhythm (intertap interval SD, -46.4% [95% CI, -63.7% to -20.9%]). The speed-related endpoints showed a moderate-to-strong correlation with the MDS-UPDRS III (r = 0.45-0.70). The effect sizes of total taps and spatial error in the alternate index finger tapping task and opening velocity in the thumb-index finger task were comparable with the MDS-UPDRS III. In contrast, the MDS-UPDRS III performed better than the alternate index-middle finger task. Conclusion: The alternate index finger and the thumb-index finger tapping tasks provide short, rater-independent measurements that are sensitive to levodopa/carbidopa effects with a similar effect size as the MDS-UPDRS III. Show less
Background: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces... Show moreBackground: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. Improving mitochondrial function has been proposed as an opportunity to treat HD, but it is not known how mitochondrial function in different tissues relates.Objective: We explored associations between central and peripheral mitochondrial function in a group of mild to moderate staged HD patients.Methods: We used phosphorous magnetic resonance spectroscopy (31P-MRS) to measure mitochondrial function in vivo in the calf muscle (peripheral) and the bio-energetic state in the visual cortex (central). Mitochondrial function was also assessed ex vivo in circulating peripheral blood mononuclear cells (PBMCs). Clinical function was determined by the Unified Huntington's Disease Rating Scale (UHDRS) total motor score. Pearson correlation coefficients were computed to assess the correlation between the different variables.Results: We included 23 manifest HD patients for analysis. There was no significant correlation between central bio-energetics and peripheral mitochondrial function. Central mitochondrial function at rest correlated significantly to the UHDRS total motor score (R = -0.45 and -0.48), which increased in a subgroup with the largest number of CAG repeats.Discussion: We did not observe a correlation between peripheral and central mitochondrial function. Central, but not peripheral, mitochondrial function correlated to clinical function. Muscle mitochondrial function is a promising biomarker to evaluate disease-modifying compounds that improve mitochondrial function, but Huntington researchers should use central mitochondrial function to demonstrate proof-of-pharmacology of disease-modifying compounds. Show less
The Netherlands-Flemish Institute in Cairo (NVIC) held a seminar entitled 'A Pioneer of Islamic Studies in Hungary: Ignaz Goldziher (1850-1921) and his Significance for the 21st Century' on 4... Show moreThe Netherlands-Flemish Institute in Cairo (NVIC) held a seminar entitled 'A Pioneer of Islamic Studies in Hungary: Ignaz Goldziher (1850-1921) and his Significance for the 21st Century' on 4 October 2000, in co-operation with the Hungarian Embassy in Cairo. The work of Ignaz Goldziher can still be regarded as seminal for numerous fields within Arabic and Islamic Studies. Show less