| 1. |
- Boman, Andrea, et al.
(författare)
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Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
- 2016
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 6:2, s. 307-315
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy is hampered by overlapping symptomatology and lack of biomarkers for diagnosis, and definitive diagnosis is only possible post-mortem. Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that levels and profiles of lysosomal network proteins in cerebrospinal fluid could be changed in these parkinsonian syndromes.Methods: Cerebrospinal fluid samples were collected from Parkinson’s disease patients (n=18), clinically diagnosed 4-repeat tauopathy patients, corticobasal syndrome (n=6) and progressive supranuclear palsy (n=5), pathologically diagnosed progressive supranuclear palsy (n=8) and corticobasal degeneration patients (n=7). Each patient set was compared to its appropriate control group consisting of the same number of age and gender matched individuals. Lysosomal network protein levels were detected via Western blotting.Results: Lysosomal network proteins have markedly different cerebrospinal fluid protein levels and profiles in Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in Parkinson´s disease; early endosomal antigen 1 was decreased and lysozyme increased in progressive supranuclear palsy; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in corticobasal degeneration.Conclusions: Lysosomal network proteins hold promise of being interesting novel candidates for biomarker studies and for elucidating disease mechanisms of Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy, but further validation studies will be needed to assess the specificity and the predictive value of these proteins in CSF.
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| 2. |
- de Roos, Paul, et al.
(författare)
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A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement
- 2017
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 7:3, s. 533-543
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential.OBJECTIVE: Propose a global consensus standard set of outcome measures for PD.METHODS: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected.RESULTS: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment.CONCLUSIONS: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions.
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| 3. |
- Georgiopoulos, Charalampos, et al.
(författare)
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Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.
- 2017
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Ingår i: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7:2, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.
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| 4. |
- Hariz, Gun-Marie, et al.
(författare)
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"DBS means everything - for some time" : Patients' Perspectives on Daily Life with Deep Brain Stimulation for Parkinson's Disease
- 2016
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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 6:2, s. 335-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. However, patients' own perceptions of the impact of DBS on their daily living is not fully explored. Objective: We aimed to collect and analyse patients' narratives about their everyday experiences of being on chronic DBS. Methods: Semi-structured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions were related to patients' ordinary daily life and eventual changes, both negative and positive, brought about by DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in grounded theory. Results: From the patients' narratives the core category `DBS means everything - for some time' was established, and supported by the following categories: 1) Relief from invasive tremor. 2) A rescue from cramps and pain. 3) Easier movement swings and more predictable living space. 4) Hard, but compared to previous suffering, bearable adverse events. 5) Parkinson's disease is progressing despite DBS. Conclusions: The analysis of the participants' narratives shed light on patients' unique perceptions and perspectives of the impact of DBS on their everyday lives. Patients with advanced PD highly appreciated the positive impact of DBS on their daily life even if this impact is limited in time. For the majority, the relief from the severe parkinsonian symptoms, especially tremor and painful cramps, outweighed the side effects of DBS. The study provided information not readily captured by pre-formulated questionnaires and scales.
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| 5. |
- Hariz, Marwan
(författare)
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My 25 Stimulating Years with DBS in Parkinson's Disease
- 2017
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Ingår i: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7, s. S35-S43
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Forskningsöversikt (refereegranskat)abstract
- The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson's disease (PD). STN DBS is undoubtedly "the most important discovery since levodopa", as stated by David Marsden in 1994. In 2014, The Lasker-DeBakey Clinical Medical Research Award to "honor two scientists who developed deep brain stimulation of the subthalamic nucleus", was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a "closed-loop", "on demand" stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient's quality of life, I consider that the surgery should be tailored to the patient's individual symptoms and needs, and that its safety is paramount.
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| 6. |
- Lenfeldt, Niklas, et al.
(författare)
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Fractional Anisotropy and Mean Diffusion as Measures of Dopaminergic Function in Parkinson's Disease : Challenging Results
- 2017
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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 7:1, s. 129-142
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson’s disease.Objective: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT.Methods: One-hundred and eleven patients with Parkinson’s disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13). Four equipment combinations of MRI scanners/SPECT gamma cameras were used during the study. Data from each combination were analyzed separately. Regions-of-interest were outlined in the substantia nigra (three subareas, DTI only) and in the striatum (putamen and caudate). Side differences and bilateral averages were correlated using linear regression. The significance threshold was set at P < 0.001 and 0.001 < P< 0.05 was defined as a trend towards significance.Results: For side differences, no significant correlations were observed, but in patients, there was a trend towards a negative correlation between MD in the middle nigra and putaminal DAT uptake in two combinations (P = 0.04 and P = 0.03). For averages, in patients, striatal MD correlated negatively with striatal DAT uptake in one combination (P = 0.0005) and trended towards negative correlations with striatal D2R uptake (one combination, P = 0.03) and with the sum of striatal DAT and D2R uptake (two combinations P = 0.002 and P = 0.03). FA showed no correlations in patients, and no correlations were found in controls.Conclusions: The poor correlations between MD and dopamine activity –and absent correlations for FA – imply that additional diffusion measures must be developed to reliably assess the dopaminergic degeneration in Parkinson’s disease.
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| 7. |
- Mitra, Reinika, et al.
(författare)
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Local Change in Urinary Bladder Contractility Following CNS Dopamine Denervation in the 6-OHDA Rat Model of Parkinson's Disease
- 2015
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Ingår i: Journal of Parkinsons Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 5:2, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson's disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration. Objective: In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson's disease with that of normal untreated animals. Methods: The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an vitro organ bath setup. Results: Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20-40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10(-4) Mconcentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5x10(-3) M) during atropine treatment. Conclusions: Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson's disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson's disease that has previously not been described.
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| 8. |
- Olsson, Yvonne, et al.
(författare)
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Health and Social Service Access Among Family Caregivers of People with Parkinson's Disease
- 2016
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Ingår i: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 6:3, s. 581-587
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Tidskriftsartikel (refereegranskat)abstract
- Background: Being a family caregiver for a person with Parkinson's disease (PD) can negatively impact health and wellbeing, but it appears less clear to what extent caregivers' health/social service needs are met. Objective: We explored the extent to which PD family caregivers experience sufficient access to health/social services, as compared to age-matched controls; and the associations between this and demographic and health-related variables. Methods: A cross-sectional survey of 66 PD family caregivers and 79 age-matched control subjects including the SF-36 health survey, the Nottingham Health Profile Sleep section (NHP-Sleep), and questions regarding contacts with various health/social related services and whether these were perceived as sufficient. Results: People reporting insufficient access (n = 29) were more often PD family caregivers than controls (83% vs. 37%), did more often have a disease of their own (79% vs. 46%), and reported poorer health according to the SF-36 and the NHP-Sleep. Being a PD family caregiver (OR, 8.90), reporting more pain (OR, 1.02) and having an own disease (OR, 3.46) were independently associated with insufficient health/social service access. Conclusions: Our results imply that those in greatest need for health/social services (i.e., those with poorer health, an own disease, and who are PD family caregivers) are those whose health/social service needs are least met. Larger studies are needed for firmer conclusions and regarding how unmet health/social service needs impacts caregiver health and wellbeing. Health/social service providers should not only focus on patients but also consider their family members' needs.
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| 9. |
- Petersson, Per, et al.
(författare)
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Significance and Translational Value of High-Frequency Cortico-Basal Ganglia Oscillations in Parkinson's Disease
- 2019
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 9:1, s. 183-196
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms and significance of basal ganglia oscillations is a fundamental research question engaging both clinical and basic investigators. In Parkinson's disease (PD), neural activity in basal ganglia nuclei is characterized by oscillatory patterns that are believed to disrupt the dynamic processing of movement-related information and thus generate motor symptoms. Beta-band oscillations associated with hypokinetic states have been reviewed in several excellent previous articles. Here we focus on faster oscillatory phenomena that have been reported in association with a diverse range of motor states. We review the occurrence of different types of fast oscillations and the evidence supporting their pathophysiological role. We also provide a general discussion on the definition, possible mechanisms, and translational value of synchronized oscillations of different frequencies in cortico-basal ganglia structures. Revealing how oscillatory phenomena are caused and spread in cortico-basal ganglia-thalamocortical networks will offer a key to unlock the neural codes of both motor and non-motor symptoms in PD. In preclinical therapeutic research, recording of oscillatory neural activities holds the promise to unravel mechanisms of action of current and future treatments.
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| 10. |
- Riggare, Sara, et al.
(författare)
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Precision Medicine in Parkinson's Disease - : Exploring Patient-Initiated Self-Tracking
- 2018
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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 8:3, s. 441-446
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Individually tailored healthcare, in the form of precision medicine, holds substantial potential for the future of medicine, especially for a complex disorder like Parkinson's disease (PD). Patient self-tracking is an under-researched area in PD.OBJECTIVE: This study aimed to explore patient-initiated self-tracking in PD and discuss it in the context of precision medicine.METHODS: The first author used a smartphone app to capture finger-tapping data and also noted times for medication intakes.RESULTS: Data were collected during four subsequent days. Only data from the first two days were complete enough to analyze, leading to the realization that the collection of data over a period of time can pose a significant burden to patients. From the first two days of data, a dip in finger function was observed around the time for the second medication dose of the day.CONCLUSIONS: Patient-initiated self-tracking enabled the first author to glean important insights about how her PD symptoms varied over the course of the day. Symptom tracking holds great potential in precision medicine and can, if shared in a clinical encounter, contribute to the learning of both patient and clinician. More work is needed to develop this field and extra focus needs to be given to balancing the burden of tracking for the patient against any expected benefit.
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