| 1. |
- Francardo, Veronica, et al.
(författare)
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Investigating the molecular mechanisms of L-DOPA-induced dyskinesia in the mouse
- 2014
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Ingår i: Parkinsonism and Related Disorders. - 1353-8020. ; 20:SUPPL.1, s. 20-22
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic supersensitivity of D1-receptor dependent signaling pathways throughout the striatum. In contrast, mice with striatal 6-OHDA lesions have been found to exhibit a variable susceptibility to LID and a regionally restricted post-synaptic supersensitivity. Genetic mouse models of PD have just started to be used for studies of LID, providing an opportunity to dissect the impact of genetic factors on the maladaptive neuroplasticity that drives the development of treatment-induced involuntary movements in PD.
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| 2. |
- Hagell, Peter
(författare)
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Nursing and multidisciplinary interventions for Parkinson's disease : what is the evidence?
- 2007
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 13:Suppl 3, s. 501-508
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the interim results of an ongoing systematic review of the available evidence for the effectiveness of nursing care for people with Parkinson's disease (PD). Five clinical and four health-economic evaluations suggest that the clinical and cost effectiveness of nursing care for PD remain inconclusive. This is in contrast to clinical experience and may be due to issues related to study designs, study interventions, and the outcome measures used. More studies are needed and may benefit from considering specific interventions evaluated using outcome measures that are valid and responsive representations of their expected outcomes.
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| 3. |
- 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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| 4. |
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| 5. |
- Hariz, Gun-Marie, et al.
(författare)
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Gender distribution in surgery for Parkinson's disease.
- 2000
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Ingår i: Parkinsonism & Related Disorders. - 1353-8020 .- 1873-5126. ; 6:3, s. 155-157
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) affects both women and men. The surgical treatment of this disease has experienced a worldwide increase since the mid-eighties. In order to document eventual differences in gender distribution of patients undergoing various stereotactic surgical procedures for PD, we reviewed scientific papers published during the last 14years.A literature search provided 145 clinical papers, published between January 1985 and February 1999, and dealing with pallidotomy, thalamotomy and deep brain stimulation procedures. These papers were scrutinised with respect to redundancies or other overlap of reported patients. The resulting numbers of patients were compiled according to gender, to surgical procedure, and to geographic area of origin of the publishing centers.In one third of the reviewed publications the gender of the patients was not specified. In the remaining papers, the overall sex distribution of patients who underwent surgery was 35% females and 65% males. These proportions between sexes were relatively consistent regardless of surgical procedure, and regardless of geographic origin of the publications.Male preponderance in patients undergoing surgery for PD cannot be explained by a corresponding difference in gender-prevalence of the disease. The criteria of selection, and patterns of referral, of patients for surgery, as well as the respective attitude of female and male patients toward surgery, may account for the uneven gender distribution in surgical PD patients.
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| 6. |
- Hariz, Marwan
(författare)
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Deep brain stimulation : new techniques
- 2014
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 20:Suppl.1, s. S192-S196
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Tidskriftsartikel (refereegranskat)abstract
- The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago.However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects.Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously.Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Albrecht, F., et al.
(författare)
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Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data
- 2022
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 102, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. Methods: Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. Results: Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. Conclusions: Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.
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| 14. |
- Antonini, Angelo, et al.
(författare)
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Levodopa-carbidopa intestinal gel in advanced Parkinson's : Final results of the GLORIA registry
- 2017
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 45, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. Methods: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. Results: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). Conclusions: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.
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| 15. |
- Antonini, Angelo, et al.
(författare)
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Validation and clinical value of the MANAGE-PD tool : A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications
- 2021
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 92, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. Methods: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts’ clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). Results: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). Conclusions: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.
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| 16. |
- Aquilonius, SM, et al.
(författare)
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Introduction
- 2004
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Ingår i: PARKINSONISM & RELATED DISORDERS. - : Elsevier BV. - 1353-8020. ; 10:5, s. 257-258
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
- 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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| 18. |
- Bech, Sara, et al.
(författare)
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Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes.
- 2012
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 18:1, s. 69-72
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Tidskriftsartikel (refereegranskat)abstract
- Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) in the diagnosing of PS. We investigated the levels of the light subunit of neurofilament triplet protein (NF-L), total tau and phosphorylated tau, amyloid-β(1-42), and the soluble α- and β-cleaved fragments of amyloid precursor proteins in a cohort of patients with various PS.
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| 19. |
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| 20. |
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| 21. |
- Blomstedt, Patric, et al.
(författare)
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Acute severe depression induced by intraoperative stimulation of the Substatia Nigra : a case-report
- 2008
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 14:3, s. 253-256
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We present a 62 years old man with Parkinson's disease (PD) who underwent bilateral stimulation in the subthalamic nucleus (STN). During the intraoperative evaluation, stimulation through the lowest contact in the right STN area, induced an acute depressive state, during which the patient was crying and expressing that he did not want to live. The patient returned to his normal state of mood within seconds after the cessation of stimulation. Repeated blinded stimulations resulted in the same response. Immediate postoperative magnetic resonance imaging (MRI) revealed that the lowest contact of the right electrode was located in the substantia nigra.
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| 22. |
- Blomstedt, Patric, et al.
(författare)
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Deep brain stimulation for movement disorders before DBS for movement disorders
- 2010
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 16:7, s. 429-433
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is an established surgical treatment for Parkinson's disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD. This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using "therapeutic electrical stimulation" through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson's disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.
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| 23. |
- Blomstedt, Patric, et al.
(författare)
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Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 17:8, s. 617-620
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.
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| 24. |
- Blomstedt, Patric, et al.
(författare)
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Pallidotomy versus pallidal stimulation
- 2006
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 12:5, s. 296-301
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Tidskriftsartikel (refereegranskat)abstract
- Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on–off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22–60) after the pallidotomy and 22 months (range 12–33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20–26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.
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| 25. |
- Blomstedt, Patric, et al.
(författare)
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Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor
- 2012
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:10, s. 1062-1066
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Tidskriftsartikel (refereegranskat)abstract
- Background: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinsons disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinsons disease. less thanbrgreater than less thanbrgreater thanMethods: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 +/- 6.1 years and the disease duration 7 +/- 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery. less thanbrgreater than less thanbrgreater thanResults: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (533%) of the patients. less thanbrgreater than less thanbrgreater thanConclusion: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.
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| 26. |
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| 27. |
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| 28. |
- Cappon, Davide, et al.
(författare)
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Globus pallidal deep brain stimulation for Tourette syndrome : Effects on cognitive function
- 2019
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 69, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS.Methods: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test).Results: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test.Conclusions: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.
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| 29. |
- Carmine Belin, Andrea, et al.
(författare)
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S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden.
- 2007
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020. ; 13:5, s. 295-8
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that removes ubiquitin from the C-terminal end of substrates and a component of the ubiquitin-proteasome system. A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD). We investigated the association of S18Y in our Swedish PD material. The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case-control material, supporting the hypothesis of a protective function.
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| 30. |
- Carta, Manolo, et al.
(författare)
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Involvement of the serotonin system in L-dopa-induced dyskinesias
- 2008
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 14:Suppl 2, s. 8-154
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Tidskriftsartikel (refereegranskat)abstract
- The ability of L-dopa to relieve the motor impairments in Parkinson's disease patients declines over time, and side-effects, such as dyskinesias, appear--limiting the use of the drug in the advanced stage of the disease. Serotonergic neurons are able to convert L-dopa to dopamine and to store this neurotransmitter in synaptic vesicles. This peculiarity might be very important in the advanced disease, when most of the dopaminergic neurons have degenerated. Indeed, an increasing body of evidence points to dopamine released as a false neurotransmitter from the serotonin terminals as the main pre-synaptic determinant of L-dopa-induced dyskinesias in animal models of Parkinson's disease. These findings make the serotonin system an intriguing target for anti-dyskinetic therapies.
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| 31. |
- Chaudhuri, K. Ray, et al.
(författare)
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Parkinson's disease: The non-motor issues
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 17:10, s. 717-723
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Forskningsöversikt (refereegranskat)abstract
- Non-motor symptoms (NMS) of Parkinson's disease remain the most under-appreciated and under-researched when taken as a whole. Data is emerging that it is the "totaL" burden of NMS that is the major determinant of quality of life not a single NMS such as depression for instance. Only recently validated tools such as the NMSQuest which empowers patients to declare NMS and the NMS scale, the SCOPA scales, and the modified version of the MDS-UPDRS have become available and validated for bedside clinical assessment of NMS. For the first time clinical trials have been incorporating non-motor measures as outcome measures and clinical recommendations for treatment of non-motor symptoms of PD are being published. This review aims to address some of these topical and "real life" aspects of modern day management of Parkinson's. (C) 2011 Published by Elsevier Ltd.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Levels of brain related proteins in cerebrospinal fluid: An aid in the differential diagnosis of parkinsonian disorders.
- 2009
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020. ; 15:3, s. 205-12
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Forskningsöversikt (refereegranskat)abstract
- Parkinsonian disorders such as Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a large group of common neurodegenerative diseases. The initial differential diagnosis can be extremely challenging with major implications for prognosis. The 42 amino acid fragment of amyloid-beta (Abeta42), neurofilament light chain (NFL), neurofilament heavy chain (pNFH), tau protein, glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), S-100B protein, and myelin basic protein (MBP) are brain related proteins (BRP) present in neurons and glia cells. They are released in the cerebrospinal fluid (CSF) after brain tissue damage caused by a variety of neurological diseases, including the parkinsonian disorders. A review of the literature shows that, carefully interpreted, the CSF levels of BRP can be of value in the differential diagnosis of parkinsonian disorders.
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| 36. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Levels of the light subunit of neurofilament triplet protein in cerebrospinal fluid in Huntington's disease.
- 2009
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020. ; 15:3, s. 245-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurofilaments are major structural elements of neuronal cells. The light subunit of neurofilament triplet protein (NFL) has been shown to be increased in several neurological diseases (e.g. vascular, infectious, neurodegenerative), indicating axonal damage. METHODS: In this study we analyzed the NFL levels in all (N=35) available cerebrospinal fluid (CSF) samples from a clinical trial in Huntington's disease (HD) and compared them to age and gender matched controls. RESULTS: The CSF-NFL levels were significantly higher in HD subjects compared with age and genders matched controls, and were correlated with scores on the Unified Huntington's Disease Rating Scale Total Functional Capacity assessment. The potential of CSF-NFL levels as a disease activity marker in HD needs to be further investigated.
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| 37. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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| 38. |
- 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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| 39. |
- Dobloug, S., et al.
(författare)
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A Swedish SCA34 family with late onset ataxia, cerebellar atrophy and ocular movement abnormalities with a novel mutation in ELOVL4
- 2023
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Ingår i: Parkinsonism & Related Disorders. - 1353-8020. ; 113:Suppl, s. 72-72
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Konferensbidrag (refereegranskat)abstract
- Background: To investigate the clinical and radiological presentation of anew ELOVL4mutation in a Swedish family.Methods:We compiled information on a Swedish family with 6 affectedmembers. Four of these had undergone neurological and radiological examinations. Two patients were independently analysed genetically bywhole exome or whole genome sequencing.Results: All examined affected family members showed slowly progressivecerebellar ataxia with balance impairment starting at between 42 and 70years, ocular movement disturbances with nystagmus, hypermetric saccades or vertical gaze palsy, and cerebellar atrophy on imaging. None of theaffected family members had erytrokeratodermia variabilis, but three haddry skin or psoriasis. Two members had seizures, one had intermittentmuscular cramps. One deceased obligate carrier had dementia and one ofthe members examined had mild cognitive dysfunction (MMSE 23/30). Oneindividual had poor night vision. One individual had a diagnosis ofschizophrenia since age 25 years. We identified a novel heterozygousvariant ELOVL4 c.511A>C, p.(Ile171Leu) (NM_022726.4) in affected individuals. When this was discovered in the first family member it was reported as a variant of uncertain significance (VUS). However, aftersegregation analysis and detailed clinical information for the entire family,the variant could be reclassified as likely pathogenic according to the ACMG classification system (PMID: 25741868) and Jarvik et al (PMID: 27236918).Conclusions: So far, including the present report, eight different ELOVL4-variants have been described in SCA34 patients. Our examinations provideadditional knowledge to the presentation of this rare neurodegenerativedisorder.
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| 40. |
- Donaghy, P. C., et al.
(författare)
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The relationship between plasma biomarkers and amyloid PET in dementia with Lewy bodies
- 2022
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 101, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Amyloid-β (Aβ) deposition is common in dementia with Lewy bodies (DLB) and has been associated with more rapid disease progression. An effective biomarker that identified the presence of significant brain Aβ in people with DLB may be useful to identify and stratify participants for research studies and to inform prognosis in clinical practice. Plasma biomarkers are emerging as candidates to fulfil this role. Methods: Thirty-two participants with DLB had brain amyloid (18F-florbetapir) PET, of whom 27 also had an MRI to enable the calculation of 18F-florbetapir SUVR. Plasma Aβ42/40, phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) were measured using single molecule array (Simoa). The plasma biomarkers were investigated for correlation with 18F-florbetapir SUVR, discriminant ability to identify Aβ-positive cases based on a predefined SUVR threshold of 1.10 and correlation with subsequent cognitive decline over one year. Results: All four plasma markers significantly correlated with 18F-florbetapir SUVR (|β| = 0.40-0.49; p < .05). NfL had the greatest area under the receiver operating characteristic curve to identify Aβ-positive cases (AUROC 0.84 (95% CI 0.66, 1); β = 0.46, p = .001), whereas Aβ42/40 had the smallest (AUROC 0.73 (95% CI 0.52, 0.95); β = −0.47, p = .01). Accuracy was highest when combining all four biomarkers (AUROC 0.92 (95% CI 0.80, 1)). Lower plasma Aβ42/40 was significantly associated with more rapid decline in cognition (β = 0.53, p < .01). Conclusions: Plasma biomarkers have the potential to identify Aβ deposition in DLB. Further work in other cohorts is required to determine and validate optimal cut-offs for these biomarkers. © 2022 The Authors
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| 41. |
- Donker Kaat, Laura, et al.
(författare)
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Serum neurofilament light chain in progressive supranuclear palsy.
- 2018
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 56, s. 98-101
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light chain (NfL) is a promising biomarker in neurodegenerative diseases. Elevated NfL levels in CSF and blood have been observed in a growing number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease. We studied serum NfL levels in patients with progressive supranuclear palsy (PSP) in relation to disease severity and survival.Serum NfL levels were determined cross-sectionally in a retrospective cohort of 131 patients with PSP and 95 healthy controls. Detailed clinical examination was performed and disease severity was assessed by several rating scales.We found that serum NfL levels in PSP were twice as high as those in controls, and that NfL levels correlated with worse functional, motor and cognitive functioning. During follow-up, 119 PSP patients had died, and higher NfL levels were associated with a shorter survival.This study provides evidence that serum NfL is a relevant and promising biomarker in PSP for disease severity, and may be used as a prognostic tool to predict survival in clinical practice.
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| 42. |
- Eriksson Domellöf, Magdalena, et al.
(författare)
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Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease
- 2017
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 38, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease.METHODS: Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic.RESULTS: Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44-7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia.CONCLUSIONS: Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Fernandez, Hubert H., et al.
(författare)
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Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum : Revelations from the MANAGE-PD validation cohort
- 2023
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Ingår i: Parkinsonism and Related Disorders. - 1353-8020. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories. Methods: Device-aided therapy-naïve patients receiving oral treatments were identified from the Adelphi Parkinson's Disease Programme. Patients were categorized (category 1 to 3) using MANAGE-PD. PD-specific QoL (PDQ-39), care partner burden (ZBI), satisfaction with current treatment, healthcare resource utilization, associated healthcare costs, and future treatment discussion with providers were measured. Categories were compared using ANOVA, t-test, chi square and adjusted regression analyses. Results: Of the analytical sample (n = 2709), 18.9% were inadequately controlled on current therapy and potentially eligible for device-aided therapies (category 3). As expected, they had worse patient/caregiver reported outcomes versus patients in categories 1 or 2. However, the degree of difference in healthcare resource utilization, including: greater number of hospitalizations, emergency room (ER) visits and consultations, higher likelihood of being recipients of respite care, and greater PD treatment burden, was unexpected. Importantly, of patients in category 3 and their care partners, >40% did not report discussions with providers about device-aided therapies. Conclusion: MANAGE-PD category 3 patients had significantly higher burden on healthcare resources versus patients well-controlled with oral treatment or requiring only oral medication adjustments; yet almost half had no discussion on device-aided therapies with providers. Device-aided therapies may be considered in these patients.
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