18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Holistic management of Parkinson’s disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson’s from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson’s which may manifest in a motor dominant or nonmotor dominant manner. The “advanced” stages of Parkinson’s disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of “advanced Parkinson’s disease” (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of “advanced” PD and also propose the term “complex phase” Parkinson’s disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years.

          After 20 years follow-up of newly diagnosed patients with Parkinson's disease (PD), 100 of 136 (74%) have died. The mortality rate fell in the first 3 years of treatment, then rose compared to the general population, the standardized mortality ratio from 15 to 20 years reaching 3.1. Drug induced dyskinesia and end of dose failure were experienced by most patients, but the main current problems relate to the non-levodopa responsive features of the disease. Dementia is present in 83% of 20-year survivors. Dementia correlates with increasing age and probably reflects an interplay of multiple pathologies. Seventeen people with dementia had postmortems. Eight had diffuse Lewy bodies as the only cause of dementia, while others had mixed neuropathology. Only one person lives independently and 48% are in nursing homes. Excessive daytime sleepiness is noted in 70%, falls have occurred in 87%, freezing in 81%, fractures in 35%, symptomatic postural hypotension in 48%, urinary incontinence in 71%, moderate dysarthria in 81%, choking in 48%, and hallucinations in 74%. The challenge is to understand the cellular mechanisms underlying the diverse features of advanced PD that go far beyond a lack of dopamine. (c) 2008 Movement Disorder Society.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The clinical symptoms of Parkinson's disease.

            In this review, the clinical features of Parkinson's disease, both motor and non-motor, are described in the context of the progression of the disease. Also briefly discussed are the major treatment strategies and their complications. Parkinson's disease is a slowly progressing neurodegenerative disorder, causing impaired motor function with slow movements, tremor and gait and balance disturbances. A variety of non-motor symptoms are common in Parkinson's disease. They include disturbed autonomic function with orthostatic hypotension, constipation and urinary disturbances, a variety of sleep disorders and a spectrum of neuropsychiatric symptoms. This article describes the different clinical symptoms that may occur and the clinical course of the disease. This article is part of a special issue on Parkinson disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Disease duration and the integrity of the nigrostriatal system in Parkinson's disease.

              The pace of nigrostriatal degeneration, both with regards to striatal denervation and loss of melanin and tyrosine hydroxylase-positive neurons, is poorly understood especially early in the Parkinson's disease process. This study investigated the extent of nigrostriatal degeneration in patients with Parkinson's disease at different disease durations from time of diagnosis. Brains of patients with Parkinson's disease (n=28) with post-diagnostic intervals of 1-27 years and normal elderly control subjects (n=9) were examined. Sections of the post-commissural putamen and substantia nigra pars compacta were processed for tyrosine hydroxylase and dopamine transporter immunohistochemistry. The post-commissural putamen was selected due to tissue availability and the fact that dopamine loss in this region is associated with motor disability in Parkinson's disease. Quantitative assessments of putaminal dopaminergic fibre density and stereological estimates of the number of melanin-containing and tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (both in total and in subregions) were performed by blinded investigators in cases where suitable material was available (n=17). Dopaminergic markers in the dorsal putamen showed a modest loss at 1 year after diagnosis in the single case available for study. There was variable (moderate to marked) loss, at 3 years. At 4 years post-diagnosis and thereafter, there was virtually complete loss of staining in the dorsal putamen with only an occasional abnormal dopaminergic fibre detected. In the substantia nigra pars compacta, there was a 50-90% loss of tyrosine hydroxylase-positive neurons from the earliest time points studied with only marginal additional loss thereafter. There was only a ∼10% loss of melanized neurons in the one case evaluated 1 year post-diagnosis, and variable (30 to 60%) loss during the first several years post-diagnosis with more gradual and subtle loss in the second decade. At all time points, there were more melanin-containing than tyrosine hydroxylase-positive cells. Loss of dopaminergic markers in the dorsal putamen occurs rapidly and is virtually complete by 4 years post-diagnosis. Loss of melanized nigral neurons lags behind the loss of dopamine markers. These findings have important implications for understanding the nature of Parkinson's disease neurodegeneration and for studies of putative neuroprotective/restorative therapies.
                Bookmark

                Author and article information

                Contributors
                ray.chaudhuri@nhs.net
                Journal
                J Neural Transm (Vienna)
                J Neural Transm (Vienna)
                Journal of Neural Transmission
                Springer Vienna (Vienna )
                0300-9564
                1435-1463
                7 November 2017
                7 November 2017
                2017
                : 124
                : 12
                : 1529-1537
                Affiliations
                [1 ]ISNI 0000 0000 9559 0613, GRID grid.78028.35, Department of Neurology, Neurosurgery and Medical Genetics, , Federal State Budgetary Educational Institution of Higher Education « N.I. Pirogov Russian National Research Medical University » of the Ministry of Healthcare of the Russian Federation, ; Moscow, Russia
                [2 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, ; Madrid, Spain
                [3 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, National Parkinson Foundation International Centre of Excellence, Kings College Hospital and The Maurice Wohl Clinical Neuroscience Institute, Kings College, ; 5 Cutcombe Road, London, SE59RT UK
                Article
                1799
                10.1007/s00702-017-1799-3
                5686262
                29116411
                a8551624-51f8-47d9-b6be-164d0c7729af
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 16 September 2017
                : 13 October 2017
                Funding
                Funded by: PDNMG
                Categories
                High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article
                Custom metadata
                © Springer-Verlag GmbH Austria, part of Springer Nature 2017

                parkinson’s disease,advanced,complex,nonmotor symptoms,personalised medicine,nonmotor subtypes

                Comments

                Comment on this article