| 1. |
- Bergquist, Filip, 1970, et al.
(author)
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Parkinson's disease - heterogeneous and complex in its clinical presentation.
- 2020
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 117
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Journal article (peer-reviewed)abstract
- Parkinson's disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson's disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson's disease.
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| 2. |
- Feldman, Adina L., et al.
(author)
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Accuracy and Sensitivity of Parkinsonian Disorder Diagnoses in Two Swedish National Health Registers
- 2012
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In: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 38:3, s. 186-193
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Journal article (peer-reviewed)abstract
- Background: Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson's disease have not been validated against clinical information. Methods: Parkinson's disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998-2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study). Results: Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years. Conclusions: Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence. Copyright (C) 2012 S. Karger AG, Basel
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| 4. |
- Hubers, Anna A M, et al.
(author)
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Suicidal ideation in a European Huntington's disease population
- 2013
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 151:1, s. 58-248
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.
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| 5. |
- Huttunen, Henri J., et al.
(author)
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Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial
- 2023
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In: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:7, s. 1209-1222
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Journal article (peer-reviewed)abstract
- Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE-PE2I. Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 6. |
- Larsson, Lena C, et al.
(author)
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Induction of operational tolerance to discordant dopaminergic porcine xenografts.
- 2003
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In: Transplantation. - 1534-6080 .- 0041-1337. ; 75:9, s. 1448-1454
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Journal article (peer-reviewed)abstract
- BACKGROUND: Porcine embryonic neural tissue transplanted intracerebrally could potentially relieve the symptoms of Parkinson's disease if the immune response toward the graft could be overcome. However, conventional immunosuppressive treatments have proven inefficient in preventing rejection. An alternative is blocking the costimulatory signals for lymphocyte activation. Treatment with cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA4Ig) and anti-CD40L has been successful in preventing rejection of xenografts in some experimental studies, but not all. Lymphocyte function antigen (LFA)-1 is an important costimulatory molecule for CD8+ T cells, and we hypothesize that blockade with anti-LFA-1 may enhance the efficacy of CTLA4Ig and anti-CD40L therapy. METHODS: C57BL/6 mice received intracerebral transplants of ventral mesencephalic tissue from embryonic porcine donors. CTLA4Ig, anti-CD40L, and anti-LFA-1 were administered every other day on days 0 to 8, and the transplants were studied after 4 to 6 weeks. Grafts were histologically analyzed for size, survival of dopaminergic nerve cells, and immune responses. Recipients were challenged with cultured glia cells of donor origin or an allogeneic skin graft to evaluate tolerance induction. RESULTS: Mice treated with all three substances had large grafts containing high amounts of dopamine cells but a low degree of immune response. Grafts in recipients challenged with glial cells showed an increased immunologic activity but were not rejected. Triple-treated mice showed a normal rejection process of the allogeneic skin grafts. CONCLUSION: After a short course of costimulation blocking therapy, discordant neural xenografts demonstrate long-term survival, withstand immunologic challenge, yet maintain host-versus-graft reactivity. Anti-LFA-1 complements CTLA4Ig and anti-CD40L in the induction of operational tolerance to these xenografts.
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| 7. |
- Lundin, Anders, et al.
(author)
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Efficacy and Safety of the Dopaminergic Stabilizer Pridopidine (ACR16) in Patients With Huntington's Disease
- 2010
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In: Clinical neuropharmacology. - 0362-5664 .- 1537-162X. ; 33:5, s. 260-264
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD). Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). The primary outcome measure was the change from baseline in weighted cognitive score, assessed by cognitive tests (Symbol Digit Modalities, verbal fluency, and Stroop tests). Secondary outcome measures included changes in the Unified Huntington's Disease Rating Scale, Hospital Anxiety and Depression Scale, Leeds Sleep Evaluation Questionnaire, Reitan Trail-Making Test A, and Clinical Global Impression of Change. Safety assessments were also performed. Results: There was no significant difference between pridopidine and placebo in the change from baseline of the weighted cognitive score. However, secondary measures such as affective symptoms showed trends toward improvement, and there was significant improvement in voluntary motor symptoms compared with placebo (P<0.05). Pridopidine was well tolerated, with a safety profile similar to placebo. Conclusions: Pridopidine shows promise as a treatment for some of the symptoms of HD. In this small-scale study, the most notable effect was improvement in voluntary motor symptoms. Larger, longer-term trials are warranted.
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| 8. |
- Memedi, Mevludin, et al.
(author)
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Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease
- 2015
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In: IEEE journal of biomedical and health informatics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2194 .- 2168-2208. ; 19:6, s. 1829-1834
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.
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| 9. |
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| 10. |
- Pålhagen, S. E., et al.
(author)
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Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease
- 2012
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 126:6, s. e29-e33
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Journal article (peer-reviewed)abstract
- Background - This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care. Methods - Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, andgt;= 3 months after surgery, and then every 3 months. Results - Twenty-seven treatment-naive subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean +/- SD), baseline = 52.1 +/- 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 +/- 16.7, N = 27, P = 0.003; month 12 = 42.5 +/- 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean +/- SD), baseline = 33.6 +/- 10.8, N = 27, month 0 = 27.1 +/- 11.8, N = 27, P = 0.001; 12 months = 28.8 +/- 12.8, n = 23, P = 0.126. Conclusions - LCIG provides functional improvement beginning at first visit that is sustained for 12 months.
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