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- Chelban, V., et al.
(författare)
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Neurofilament light levels predict clinical progression and death in multiple system atrophy
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:12, s. 4398-4408
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Tidskriftsartikel (refereegranskat)abstract
- In this large multiple system atrophy cohort, Chelban et al. show that plasma NfL correlates with clinical disease severity, progression and prognosis, and could help inform patient stratification and monitor treatment responses in future trials of putative disease-modifying agents. Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.
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- Gunton, L. M., et al.
(författare)
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Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage
- 2021
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Ingår i: Zookeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :1020, s. 1-198
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Tidskriftsartikel (refereegranskat)abstract
- In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42 degrees S, to southern Queensland, 24 degrees S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.
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- Schrag, A., et al.
(författare)
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The late stage of Parkinson's –results of a large multinational study on motor and non-motor complications
- 2020
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 75, s. 91-96
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: There is little information on the late stages of parkinsonism. Methods: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. Results: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. Conclusion: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.
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- 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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- Kageyama, Masa, et al.
(författare)
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A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka : sea ice data compilation and model differences
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 37-62
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Tidskriftsartikel (refereegranskat)abstract
- The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations.
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