| 1. |
- Cenci, M. Angela, et al.
(författare)
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Dyskinesia matters
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:3, s. 392-396
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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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| 2. |
- Martino, Davide, et al.
(författare)
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Association and Familial Coaggregation of Idiopathic Dystonia with Psychiatric Outcomes
- 2020
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Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35:12, s. 2270-2278
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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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| 3. |
- Mataix-Cols, David, et al.
(författare)
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Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood
- 2023
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:8, s. 1419-1427
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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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| 4. |
- Mataix-Cols, David, et al.
(författare)
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Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder
- 2021
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 36:1, s. 188-195
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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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| 5. |
- Niemelä, Valter, et al.
(författare)
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Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:2, s. 481-491
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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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| 6. |
- Pal, Gian, et al.
(författare)
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Genetic Testing in Parkinson's Disease.
- 2023
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Ingår i: Movement Disorders. - 0885-3185 .- 1531-8257. ; 38:8, s. 1384-1396
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Tidskriftsartikel (refereegranskat)abstract
- Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 7. |
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| 8. |
- Saunders-Pullman, Rachel, et al.
(författare)
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International Genetic Testing and Counseling Practices for Parkinson's Disease.
- 2023
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Ingår i: Movement Disorders. - 0885-3185 .- 1531-8257. ; 38:8, s. 1527-1535
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct-to-consumer testing.OBJECTIVES: The aim is to determine the international landscape of genetic testing in PD to inform future worldwide recommendations.METHODS: A web-based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership.RESULTS: Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region-dependent differences in access to and availability of testing and counseling were most notable in Africa. High-income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan-American and Asian countries.CONCLUSIONS: This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.
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| 9. |
- Svenningsson, P., et al.
(författare)
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A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:6, s. 1046-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 mu M on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. (c) 2020 International Parkinson and Movement Disorder Society
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