| 1. |
- Devos, David, et al.
(författare)
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Trial of Deferiprone in Parkinson’s Disease
- 2022
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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| 2. |
- Eusebio, Alexandre, et al.
(författare)
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Effects of low-frequency stimulation of the subthalamic nucleus on movement in Parkinson's disease.
- 2008
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 209:1, s. 125-30
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Tidskriftsartikel (refereegranskat)abstract
- Excessive synchronization of basal ganglia neural activity at low frequencies is considered a hallmark of Parkinson's disease (PD). However, few studies have unambiguously linked this activity to movement impairment through direct stimulation of basal ganglia targets at low frequency. Furthermore, these studies have varied in their methodology and findings, so it remains unclear whether stimulation at any or all frequencies < or = 20 Hz impairs movement and if so, whether effects are identical across this broad frequency band. To address these issues, 18 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both subthalamic nuclei were stimulated bilaterally at 5, 10 and 20 Hz after overnight withdrawal of their medication and the effects of the DBS on a finger tapping task were compared to performance without DBS (0 Hz). Tapping rate decreased at 5 and 20 Hz compared to 0 Hz (by 11.8+/-4.9%, p=0.022 and 7.4+/-2.6%, p=0.009, respectively) on those sides with relatively preserved baseline task performance. Moreover, the coefficient of variation of tap intervals increased at 5 and 10 Hz compared to 0 Hz (by 70.4+/-35.8%, p=0.038 and 81.5+/-48.2%, p=0.043, respectively). These data suggest that the susceptibility of basal ganglia networks to the effects of excessive synchronization may be elevated across a broad low-frequency band in parkinsonian patients, although the nature of the consequent motor impairment may depend on the precise frequencies at which synchronization occurs.
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| 3. |
- Tortorelli, Luca, et al.
(författare)
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The PAU Survey : a forward modeling approach for narrow-band imaging
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- Weak gravitational lensing is a powerful probe of the dark sector, once measurement systematic errors can be controlled. In [1], a calibration method based on forward modeling, called MCCL, was proposed. This relies on fast image simulations (e.g., UFig [2, 3]) that capture the key features of galaxy populations and measurement effects. The MCCL approach has been used in [4] to determine the redshift distribution of cosmological galaxy samples and, in the process, the authors derived a model for the galaxy population mainly based on broad-band photometry. Here, we test this model by forward modeling the 40 narrow-band photometry given by the novel PAU Survey (PAUS). For this purpose, we apply the same forced photometric pipeline on data and simulations using Source Extractor [5]. The image simulation scheme performance is assessed at the image and at the catalogues level. We find good statistical agreement for the distribution of pixel values, for the magnitude-size relation and for the inter-band correlations. We also discuss the small residual differences in the magnitude distributions. A principal component analysis is then performed, in order to derive a global comparison of the narrow-band photometry between the data and the simulations. We use a 'mixing' matrix to quantify the agreement between the observed and simulated sets of Principal Components (PCs). We find good agreement, especially for the first three most significant PCs. We also compare the coefficients of the PCs decomposition. While there are slight differences for some coefficients, we find that the distributions are consistent. Together, our results show that the galaxy population model derived from broad-band photometry is in good overall agreement with the PAUS data. This offers good prospects for incorporating spectral information to the galaxy model by adjusting it to the PAUS narrow-band data using forward modeling.
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| 4. |
- Witjas, Tatiana, et al.
(författare)
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A prospective single-blind study of Gamma Knife thalamotomy for tremor
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 85:18, s. 1562-1568
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the safety and efficacy of unilateral Gamma Knife thalamotomy (GKT) for treatment of severe tremor with a prospective blinded assessment. Methods: Fifty patients (mean age: 74.5 years; 32 men) with severe refractory tremor (36 essential, 14 parkinsonian) were treated with unilateral GKT. Targeting of the ventral intermediate nucleus (Vim) was achieved with Leksell Gamma Knife with a single shot through a 4-mm collimator helmet. The prescription dose was 130 Gy. Neurologic and neuropsychological assessments including a single-blinded video assessment of the tremor severity performed by a movement disorders neurologist from another center were performed before and 12 months after treatment. MRI follow-up occurred at 3, 6, and 12 months. Results: The upper limb tremor score improved by 54.2% on the blinded assessment (p < 0.0001). All tremor components (rest, postural, and intention) were improved. Activities of daily living were improved by 72.2%. Cognitive functions remained unchanged. Following GKT, the median delay of improvement was 5.3 months (range 1-12 months). The only side effect was a transient hemiparesis associated with excessive edema around the thalamotomy in one patient. Conclusion: This blinded prospective assessment demonstrates that unilateral GKT is a safe and efficient procedure for severe medically refractory tremor. Side effects were rare and transient in this study.
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