| 1. |
- Alafuzoff, Irina, et al.
(författare)
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Staged pathology in Parkinson's disease
- 2014
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Ingår i: Parkinsonism & Related Disorders. - 1353-8020 .- 1873-5126. ; 20:Suppl. 1, s. S57-S61
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Tidskriftsartikel (refereegranskat)abstract
- There has been a tremendous development since a regional progression of pathology in subjects with Lewy bodies (LB) was initially proposed 30 years ago. The entity of dementia with Lewy bodies has been acknowledged, the main protein constituent of LBs--aggregated α-synuclein (αS)--has been identified and a stepwise progression of the pathology has been reported. Implementation of the staging strategies published provides a common ground for handling a case with a suspected α-synucleinopathy. It is always important to state the staging strategy implemented while assessing a case, as the strategy applied might influence both the reported stage of LB pathology and, ultimately, the final diagnosis of the patient.
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| 2. |
- Bakhit, Yousuf, et al.
(författare)
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Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan
- 2023
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 111
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Tidskriftsartikel (refereegranskat)abstract
- PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homo-zygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co -segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic het-erogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.
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| 3. |
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| 4. |
- Cook, Lola, et al.
(författare)
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The commercial genetic testing landscape for Parkinson's disease
- 2021
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 92, s. 107-111
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThere have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation.MethodsThe National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally.ResultsWe identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial.ConclusionThere is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.
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| 5. |
- Johansson, Anders, et al.
(författare)
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[11C]-PIB imaging in patients with Parkinson's disease : preliminary results
- 2008
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 14:4, s. 345-347
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Tidskriftsartikel (refereegranskat)abstract
- [11C]-PIB positron emission tomography ([11C]-PIB PET) is a sensitive marker of amyloid in Alzheimer's disease (AD), but its specificity has not been fully evaluated. Vascular amyloid-β deposition is common in Parkinson's disease (PD) and α-synuclein, the major component of the Lewy bodies in PD, forms amyloid fibrils. We investigated five apparently cognitively normal PD patients with [11C]-PIB PET. The results were compared to 16 patients with AD and six healthy controls from a previous study. [11C]-PIB retention was not significantly increased in our patients who all had early stage PD. Further studies of more advanced PD patients are warranted.
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| 6. |
- Johansson, Dongni, 1988, et al.
(författare)
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Evaluation of a sensor algorithm for motor state rating in Parkinson's disease
- 2019
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 64:July, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A treatment response objective index (TRIS) was previously developed based on sensor data from pronation-supination tests. This study aimed to examine the performance of TRIS for medication effects in a new population sample with Parkinson's disease (PD) and its usefulness for constructing individual dose-response models. Methods: Twenty-five patients with PD performed a series of tasks throughout a levodopa challenge while wearing sensors. TRIS was used to determine motor changes in pronation-supination tests following a single levodopa dose, and was compared to clinical ratings including the Treatment Response Scale (TRS) and six sub-items of the UPDRS part III. Results: As expected, correlations between TRIS and clinical ratings were lower in the new population than in the initial study. TRIS was still significantly correlated to TRS (r(s) = 0.23, P < 0.001) with a root mean square error (RMSE) of 1.33. For the patients (n = 17) with a good levodopa response and clear motor fluctuations, a stronger correlation was found (r(s) = 0.38, RMSE = 1.29, P < 0.001). The mean TRIS increased significantly when patients went from the practically defined off to their best on state (P = 0.024). Individual dose-response models could be fitted for more participants when TRIS was used for modelling than when TRS ratings were used. Conclusion: The objective sensor index shows promise for constructing individual dose-response models, but further evaluations and retraining of the TRIS algorithm are desirable to improve its performance and to ensure its clinical effectiveness.
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| 7. |
- Memedi, Mevludin, 1983-, et al.
(författare)
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Spiral drawing during self-rated dyskinesia is more impaired than during self-rated off
- 2013
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 19:5, s. 553-556
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to examine repeated measures of fine motor function in relation to self-assessed motor conditions in Parkinson's disease (PD).Methods: One-hundred PD patients, 65 with advanced PD and 35 patients with different disease stages have utilized a test battery in a telemedicine setting. On each test occasion, they initially self-assessed their motor condition (from 'very off' to 'very dyskinetic') and then performed a set of fine motor tests (tapping and spiral drawings).Results: The motor tests scores were found to be the best during self-rated On. Self-rated dyskinesias caused more impaired spiral drawing performance (mean = 9.8% worse, P < 0.001) but at the same time tapping speed was faster (mean = 5.0% increase, P < 0.001), compared to scores in self-rated Off.Conclusions: The fine motor tests of the test battery capture different symptoms; the spiral impairment primarily relates to dyskinesias whereas the tapping speed captures the Off symptoms.
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| 8. |
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| 9. |
- Nyholm, Dag
(författare)
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Duodopa(®) treatment for advanced Parkinson's disease : A review of efficacy and safety
- 2012
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 18:8, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Enterally administered levodopa/carbidopa gel (Duodopa(®)) is used for the treatment of advanced Parkinson's disease (PD) in patients with motor fluctuations and dyskinesias. This review summarizes the current efficacy and safety data on this drug. Clinically important differences (CID) have been used to assess whether statistical improvements in symptoms translate into meaningful improvements for the patients. A PubMed search in February 2012 found 23 papers with efficacy data and 33 with safety data. Of 11 studies reporting Unified Parkinson's Disease Rating Scale (UPDRS) III scores, 10 found improvements that met the CID of 10.8 points. Of 7 studies reporting UPDRS IV scores, 5 found improvements meeting the CID of 2.3 points. Quality of life (QoL) was assessed in 6 studies using the 8- or 39-question version of the Parkinson's disease Questionnaire, and all reported improvements meeting the CID (10 points). Due to the nature of the data, it is not possible to give exact numbers for the frequency of adverse events. However, the findings seem to be in line with a previous report stating the majority of adverse events were related to the infusion system or surgical procedure rather than the drug. In conclusion, the large majority of studies have reported that Duodopa(®) is clinically effective in relieving the symptoms of advanced PD and improving QoL in comparison with conventional therapy. High-quality randomized trials with larger patient numbers will yield greater insights into the efficacy and safety of this treatment.
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| 10. |
- Nyholm, Dag
(författare)
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The rationale for continuous dopaminergic stimulation in advanced Parkinson's disease
- 2007
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 13:Suppl.1, s. S13-S17
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Tidskriftsartikel (refereegranskat)abstract
- Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia of the brain. The degeneration of these neurons in Parkinson's disease (PD) interferes with the flow of dopamine, leading to classic motor symptoms. In early PD, enough dopaminergic neurons remain to store dopamine provided by periodic dosing with oral levodopa and relatively normal, tonic levels of dopamine release are maintained. PD progression leads to degeneration of remaining dopaminergic terminals and loss of buffering capacity for exogenous levodopa. As a result, there are supraphysiological levels of dopamine after dosing and troughs when the available dopamine has been depleted. These divergent levels are associated with dyskinesia and ‘off’ states, respectively. Treatment strategies that provide a continuous flow of dopamine and can thus mimic normal physiological dopamine stimulation have potential to improve motor control for patients with advanced PD.
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