Diagnosis and the premotor phase of Parkinson disease
ABSTRACT Clinical, neuroimaging, and pathologic studies have provided data suggesting that a variety of nonmotor symptoms can precede the classic motor features of Parkinson disease (PD) by years and, perhaps, even decades. The period when these symptoms arise can be referred to as the "premotor phase" of the disease. Here, we review the evidence supporting the occurrence of olfactory dysfunction, dysautonomia, and mood and sleep disorders, in this premotor phase of PD. These symptoms are well known in established PD and when presenting early, in the premotor phase, should be potentially considered as an integral part of the disease process. Even though information on the premotor phase of PD is rapidly accumulating, the diagnosis of premotor PD remains elusive at this time. Should a safe and effective treatment with disease-modifying or neuroprotective potential in PD become available, identifying individuals in the premotor phase will become a serious priority.
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ABSTRACT: Background: Recent studies have demonstrated that, contrary to common perception non-motor symptoms (NMS) occur and may dominate early and untreated stage of Parkinson's disease (PD). Objective: The aim of this ongoing study was to describe the overall NMS profile and burden in drug naïve PD patients (DNPD) compared to a group of long-term PD patients (LTPD, disease duration ≥15 years). Methods: Cross sectional UK data from a multicenter (16 sites) collaboration were obtained and specifically NMS dataset from validated scales were analysed in DNPD and LTPD patients. The NMS scale (NMSS) was used as the primary outcome variable. Results: Out of a current database of 468 PD patients, 57 were DNPD (58% males, mean age 64.8 years, median Hoen and Yahr stage 1) and 25 were LTPD (44%, mean age 67.6 years, median Hoen and Yahr stage 3). DNPD patients had a significantly lower (p = 0.001) NMSS score (mean 45.5, range 1-150) compared to the LTPD patients (mean 74.0, range 6-155), but 26.3% had severe and 19.3% had very severe burden of NMSS using NMSS cutoff scores. In comparison, 20.0% of the LTPD patients had severe and 60.0% very severe burden of NMS (p = 0.003). Conclusions: NMS are common in DNPD patients and over 45% may have severe to very severe burden of NMS, which is a key determinant of quality of life. In LTPD patients not only the burden of "very severe" NMS is significantly higher, but there are also differences in the profile of expression of NMS.Journal of Parkinson's Disease 06/2014; 4(3). DOI:10.3233/JPD-140372 · 1.10 Impact Factor
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ABSTRACT: BACKGROUND: In Parkinson's disease (PD), alpha-synuclein (AS) aggregates occur frequently in peripheral autonomic nervous system (pANS). Their presence in asymptomatic subjects suggests incidental Lewy-body disease (iLBD) that is thought to reflect pre-clinical PD. Cardiac involvement has been detected in post-mortem studies in both, PD and also in iLBD. In vivo documentation of cardiac AS pathology is lacking. OBJECTIVE: To prospectively assess the presence of AS aggregates in epicardial fat tissue from living subjects without parkinsonism undergoing elective cardiac surgery. MATERIAL AND METHODS: Epicardial fat tissue obtained during cardiac surgery from 91 subjects was studied by histology and immunohistochemistry. Areas more likely to contain pANS elements were selected. PD-related motor and non-motor symptoms (NMS) were assessed immediately before or after surgery. RESULTS: Small autonomic nerves, ganglia and/or tyrosine-hydroxylase positive fibres were identified in epicardial fat in each of the 91 subjects (62 male/29 female, mean age 67 years). AS aggregates were detected in 7 subjects (7.7%), and were more frequent in those aged above 70 years. In AS-positive subjects constipation and acting dreams were significantly more frequent than in the AS-negative ones. CONCLUSION: AS aggregates occur in epicardial pANS in subjects without parkinsonism, suggesting the diagnosis of iLBD. The presence in some of these subjects of non-motor symptoms such as acting dreams and constipation known to occur in premotor PD supports this interpretation. Adequate follow-up of the subjects in this study will indicate the time, if any, to progression to motor PD.Parkinsonism & Related Disorders 08/2012; 19(1). DOI:10.1016/j.parkreldis.2012.07.005 · 4.13 Impact Factor
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ABSTRACT: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed.Cold Spring Harbor Perspectives in Medicine 06/2012; 2(6):a008870. DOI:10.1101/cshperspect.a008870 · 7.56 Impact Factor