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Sökning: L773:1531 8257 > Uppsala universitet

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1.
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2.
  • Cenci, M. Angela, et al. (författare)
  • Dyskinesia matters
  • 2020
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:3, s. 392-396
  • Tidskriftsartikel (refereegranskat)abstract
    • Levodopa-induced dyskinesia (LID) represents a significant source of discomfort for people with Parkinson's disease (PD). It negatively affects quality of life, it is associated with both motor and nonmotor fluctuations, and it brings an increased risk of disability, balance problems, and falls. Although the prevalence of severe LID appears to be lower than in previous eras (likely owing to a more conservative use of oral levodopa), we have not yet found a way to prevent the development of this complication. Advanced surgical therapies, such as deep brain stimulation, ameliorate LID, but only a minority of PD patients qualify for these interventions. Although some have argued that PD patients would rather be ON with dyskinesia than OFF, the deeper truth is that patients would very much prefer to be ON without dyskinesia. As researchers and clinicians, we should aspire to make that goal a reality. To this end, translational research on LID is to be encouraged and persistently pursued.
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3.
  • Larsson, Susanna C., et al. (författare)
  • No clear support for a role for vitamin D in Parkinson's disease : A Mendelian randomization study.
  • 2017
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 32:8, s. 1249-1252
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation.METHODS: As instrumental variables for the Mendelian randomization analysis, we used 4 single-nucleotide polymorphisms that affect 25-hydroxyvitamin D concentrations (rs2282679 in GC, rs12785878 near DHCR7, rs10741657 near CYP2R1, and rs6013897 near CYP24A1). Summary effect size estimates of the 4 single-nucleotide polymorphisms on PD were obtained from the International Parkinson's Disease Genomics Consortium (including 5333 PD cases and 12,019 controls). The estimates of the 4 single-nucleotide polymorphisms were combined using an inverse-variance weighted meta-analysis.RESULTS: Of the 4 single-nucleotide polymorphisms associated with 25-hydroxyvitamin D concentrations, one (rs6013897 in CYP24A1) was associated with PD (odds ratio per 25-hydroxyvitamin D-decreasing allele, 1.09; 95% confidence interval, 1.02-1.16; P = 0.008), whereas no association was observed with the other 3 single-nucleotide polymorphisms (P > 0.23). The odds ratio of PD per genetically predicted 10% lower 25-hydroxyvitamin D concentration, based on the 4 single-nucleotide polymorphisms, was 0.98 (95% confidence interval, 0.93-1.04; P = 0.56).CONCLUSIONS: This Mendelian randomization study provides no clear support that lowered 25-hydroxyvitamin D concentration is causally associated with risk of PD. © 2017 International Parkinson and Movement Disorder Society.
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4.
  • Marrinan, Sarah L, et al. (författare)
  • A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.
  • 2018
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 33:2, s. 329-332
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.
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5.
  • Martino, Davide, et al. (författare)
  • Association and Familial Coaggregation of Idiopathic Dystonia with Psychiatric Outcomes
  • 2020
  • Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35:12, s. 2270-2278
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Psychiatric comorbidities are common and major determinants of quality of life in idiopathic dystonia. Their prevalence estimates from service-based studies are heterogeneous. Objective We explored the association between idiopathic dystonia and depressive disorders, anxiety disorders, suicide attempts, and death by suicide using Swedish population-based registers. Methods Diagnoses of idiopathic dystonia and psychiatric outcomes from inpatient and outpatient specialist services (1997-2013) were collected from the National Patient Register and the Cause of Death Register. Familial associations were explored using the Multi-Generation Register. Adjusted logistic regression analyses measured associations with psychiatric disorders in individuals with dystonia compared with general population individuals and their unaffected siblings, as well as in full siblings of individuals with dystonia compared with full siblings of unaffected individuals. Results Individuals with dystonia were more likely than those without to have a diagnosis of depressive disorder (adjusted odds ratio = 2.00, 95% confidence interval: 1.77-2.26), anxiety disorder (adjusted odds ratio = 2.13, 95% confidence interval: 1.90-2.39), and suicide attempts/death by suicide combined (adjusted odds ratio = 1.80, 95% confidence interval: 1.50-2.17), with odds higher in most idiopathic dystonia forms. In the full sibling comparison, estimates followed the same pattern, with overall attenuated magnitude. Full siblings of individuals with dystonia had higher likelihood of depressive or anxiety disorders and suicide attempts/death by suicide combined compared with siblings of individuals without dystonia. Conclusions Different forms of idiopathic dystonia confirm its association with increased risk for depressive and anxiety disorders and suicide attempts. Familial coaggregation of dystonia and these psychiatric comorbidities supports shared genetic and extragenetic factors. (c) 2020 International Parkinson and Movement Disorder Society
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6.
  • Mataix-Cols, David, et al. (författare)
  • Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood
  • 2023
  • Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:8, s. 1419-1427
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence. OBJECTIVES: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence.METHODS: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models.RESULTS: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001).CONCLUSIONS: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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7.
  • Mataix-Cols, David, et al. (författare)
  • Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder
  • 2021
  • Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 36:1, s. 188-195
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents.OBJECTIVES: The aim of this study was to investigate the risk for injuries or death caused by transport and motor vehicle accidents in individuals with Tourette syndrome or chronic tic disorder.METHODS: This population-based, sibling-controlled cohort study included all individuals aged ≥18 years living in Sweden between 1997 and 2013 (N = 6,127,290). A total of 3449 individuals had a registered diagnosis of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. We also identified 2191 families with full siblings discordant for tic disorders. Cox proportional hazards regression modeling was used to estimate the risk for injuries or deaths as a result of transport accidents in individuals with a lifetime diagnosis of Tourette syndrome or chronic tic disorder compared with unexposed individuals and siblings.RESULTS: Individuals with tic disorders had a higher risk for transport injuries or death compared with the general population (adjusted hazard ratio, 1.50 [95% confidence interval: 1.33-1.69]) and their unaffected siblings (adjusted hazard ratio, 1.41 [95% confidence interval: 1.18-1.68]). The risks were similar across sexes. The exclusion of most psychiatric comorbidities did not alter the magnitude of the estimates. However, the risks were no longer significant after exclusion of individuals with comorbid attention deficit hyperactivity disorder.CONCLUSIONS: The marginally increased risk for serious transport accidents in tic disorders is mainly driven by attention deficit hyperactivity disorder comorbidity. Improved detection and management of attention deficit hyperactivity disorder symptoms in this patient group are warranted.
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8.
  • Meppelink, Anne Marthe, et al. (författare)
  • Transcutaneous Port for Continuous Duodenal Levodopa/Carbidopa Administration in Parkinson's Disease
  • 2011
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 26:2, s. 331-334
  • Tidskriftsartikel (refereegranskat)abstract
    • Motor fluctuations in Parkinson's disease (PD) can be reduced by intraduodenal infusion of levodopa-carbidopa (Duodopa®) via percutaneous endoscopic gastrojejunostomy (PEG). We applied the transcutaneous soft-tissue anchored titanium port (T-port) in 15 PD patients with motor fluctuations; 7 Duodopa-naive (non-PEG), and 8 previously receiving Duodopa (former-PEG). Motor scores (UPDRS-III) and quality of life (QOL, PDQ-8) were assessed at baseline and 6 month follow-up. Six patients had local irritation shortly after implantation, persisting in one patient at 6 month follow-up, which led to explantation. After having finished the protocol, four T-ports were explanted in total. UPDRS-III and PDQ-8 scores improved moderately in the non-PEG patients, but remained similar in the former-PEG users. Two former-PEG users developed polyneuropathy. No obstructions, retractions, or leakages occurred. Technical and hygienic properties of the T-port were preferred by most patients. The T-port seems to be suitable for most PD patients qualifying for Duodopa therapy, although local infection may lead to explantation during longer-term follow-up.
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9.
  • Niemelä, Valter, et al. (författare)
  • Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease
  • 2021
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:2, s. 481-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies. Methods We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 pre-manifest (preHD), and 38 controls. A biologically plausible and significant possible biomarker was validated in samples from a separate cohort of patients and controls consisting of 23 ManHD patients and 23 controls. Results In ManHD compared to preHD, 10 proteins were downregulated and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin were closely linked to HD symptom severity, whereas levels of 15 upregulated proteins were associated with symptom severity. The decreased PENK levels were replicated in the separate cohort where absolute quantitation was performed. Conclusions We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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10.
  • Nyholm, Dag, et al. (författare)
  • Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson's disease
  • 2004
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 19:4, s. 446-451
  • Tidskriftsartikel (refereegranskat)abstract
    • AbstractFrequent assessment of the symptoms in Parkinson's disease (PD) is important in both clinical and experimental settings, especially when motor fluctuations are present. Patient diaries are increasingly used in studies, allowing patients to stay in their home environments. However, traditional paper diaries may not reflect reality because of a lack in compliance or retrospective data entries. This study presents a comparison between paper diaries and a new method, real-time data capture with a hand-held computer (electronic diary). Twenty patients with PD diagnosed at least 5 years previously were randomly assigned to use either a paper diary or an electronic diary on 8 days during 1 month. Questions were answered every 2 hours over a 12-hour period on each day. Median compliance was 88% with the electronic diary and 98% with the paper diary, although strict compliance to the scheduled times by patients using the paper diary was 78%. Neither age nor earlier experience with computers affected the patient's ability to use the electronic diary. Electronic diaries can be used for self-assessment of PD symptoms. The real-time feature provides fast access to clean data with knowledge of true compliance.
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