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- Hellberg, Clara, et al.
(författare)
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Nationwide prevalence of primary dystonia, progressive ataxia and hereditary spastic paraplegia
- 2019
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020. ; 69, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the nationwide prevalence of primary dystonia, ataxia and hereditary spastic paraplegia (HSP) in Sweden. Methods: We extracted data on all patients who were registered in The National Patient Register (NPR) in Sweden (population 9.64 million) at least twice during five consecutive years with a diagnosis of primary dystonia, ataxia or HSP. We excluded patients with an additional diagnosis possibly indicating secondary causes, and determined the proportion of wrongly diagnosed patients at our own tertiary center by patient examination or chart review. We analyzed patients' age and disorder subtypes, geographical distribution of patients within Sweden and the country of birth of all patients. Results: Nationwide, we identified 4239 patients (31.6% male) with a diagnosis of primary dystonia. Of 347 patients with dystonia at our center, 20.2% may have had a different final diagnosis. Extrapolation of this uncertainty rate to the national population resulted in a prevalence for primary dystonia of 35.1/100,000. There were 672 patients (49.6% male) with ataxia in NPR, and the diagnostic uncertainty rate among 81 patients in our center was 13.6% (prevalence 6.0/100,000). HSP was diagnosed in 235 patients nationwide (52.3% male, prevalence 2.4/100,000). Patients were distributed relatively evenly throughout the country. The proportions of patients with these diagnoses who were born outside of Sweden were lower (8.0-12.7%) than the proportion of all Swedish residents born abroad (15.9%). Conclusions: In this large, nationwide study, the prevalence of dystonia was high compared to previous studies, which partly may be explained by the high coverage of NPR.
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| 2. |
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| 3. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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| 4. |
- Smith, Ruben, et al.
(författare)
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18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers
- 2016
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 139:9, s. 2372-2379
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Tidskriftsartikel (refereegranskat)abstract
- Tau positron emission tomography ligands provide the novel possibility to image tau pathologyin vivo. However, little is known about howin vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with F-18-AV-1451 in three patients harbouring a p.R406W mutation in theMAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited F-18-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was F-18-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-beta (F-18-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that F-18-AV-1451 positron emission tomography can be used to accurately quantifyin vivo the regional distribution of hyperphosphorylated tau protein.
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