Analysis of the clinical features of early Parkinson's disease with comparatively integrated intestinal function.

OBJECTIVE: Constipation is among the most frequently delineated nonmotor symptoms (NMS) with a high occurrence in Parkinson's disease (PD). The purpose of our study was to investigate whether PD with comparatively integrated intestinal function (without constipation) in the early stage had different clinical features compared to constipated PD. METHOD: We conducted a study of 105 consecutive de novo as well as early treated (treated for shorter than 3 months), aged 50 years or older outpatients. Subjects were administered motor and nonmotor questionnaires as well as constipation associated examinations. Then, we explored the distinctive features of nonconstipated contrasted to constipated PD by using univariate, multiple regression analysis and correlation analysis. RESULTS: Nonconstipated PD tended to have fewer motor deficits, as well as lower Hoehn and Yahr (H&Y) stage and they mainly presented as tremor-dominant (TD), while constipated group had a higher occurrence of posture instability and gait difficulty (PIGD); nonconstipated patients were inclined to live in urban area, the NMSloads and prevalence of NMS were lower compared to constipated ones. Correlation analysis found a discord between NMSloads and disease severity based on H&Y stage and motor scores in nonconstipated PD. CONCLUSIONS: These results suggest that PD without constipation in early stage may represent a unique clinical phenotype, which may be more benign than PD with constipation.

Motor Subtypes of Parkinson's Disease Can Be Identified by Frequency Component of Postural Stability.

Parkinson's disease (PD) can be divided into two subtypes based on clinical features-namely tremor dominant (TD) and postural instability and gait difficulty (PIGD). This categorization is important at the early stage of PD, since identifying the subtypes can help to predict the clinical progression of the disease. Accordingly, correctly diagnosing subtypes is critical in initiating appropriate early interventions and tracking the progression of the disease. However, as the disease progresses, it becomes increasingly difficult to further distinguish those attributes that are relevant to the subtypes. In this study, we investigated whether a method using the standing center of pressure (COP) time series data can separate two subtypes of PD by looking at the frequency component of COP (i.e., COP position and speed). Thirty-six participants diagnosed with PD were evaluated, with their bare feet on the force platform, and were instructed to stand upright with their arms by their sides for 20 s (with their eyes open and closed), which is consistent with the traditional COP measures. Fast Fourier transform (FFT) and wavelet transform (WT) were performed to distinguish between the motor subtypes using the COP measures. The TD group exhibited larger amplitudes at the frequency range of 3-7 Hz when compared to the PIGD group. Both the FFT and WT methods were able to differentiate the subtypes. COP time series information can be used to differentiate between the two motor subtypes of PD, using the frequency component of postural stability.

Tremor and Rigidity in Patients with Parkinson's Disease: Emphasis on Epidemiology, Pathophysiology and Contributing Factors.

Parkinson's disease (PD) is the second most prominent neurodegenerative movement disorder after Alzheimer's disease, involving 2-3% of the population aged above 65 years. This is mainly triggered by the depletion of dopaminergic neurons located in substantia nigra pars compacta (SNpc) in the region of basal ganglia. At present, diagnosis for symptoms of PD is clinical, contextual, unspecified and therapeutically incomprehensive. Analysis of various causes of PD is essential for an accurate examination of the disease. Among the different causes, such as tremors and rigidity, unresponsiveness to the current treatment approach contributes to mortality. In the present review article, we describe various key factors of pathogenesis and physiology associated with tremors and rigidity necessary for the treatment of PI (postural instability) in patients with PD. Additionally, several reports showing early tremor and rigidity causes, particularly age, cortex lesions, basal ganglia lesions, genetic abnormalities, weakened reflexes, nutrition, fear of fall, and altered biomechanics, have been explored. By summarizing the factors that contribute to the disease, histopathological studies can assess rigidity and tremor in PD. With a clear understanding of the contributing factors, various prospective studies can be done to assess the incidence of rigidity and tremors.

Neuroimaging Detectable Differences between Parkinson's Disease Motor Subtypes: A Systematic Review.

BACKGROUND: The neuroanatomical substrates of Parkinson's disease (PD) with tremor-dominance (TD) and those with non-tremor dominance (nTD), postural instability and gait difficulty (PIGD), and akinetic-rigid (AR) are not fully differentiated. A better understanding of symptom specific pathoanatomical markers of PD subtypes may result in earlier diagnosis and more tailored treatment. Here, we aim to give an overview of the neuroimaging literature that compared PD motor subtypes. METHODS: A systematic literature review on neuroimaging studies of PD subtypes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms submitted to the PubMed database included: "Parkinson's disease", "MRI" and "motor subtypes" (TD, nTD, PIGD, AR). The results are first discussed from macro to micro level of organization (i.e., (1) structural; (2) functional; and (3) molecular) and then by applied imaging methodology. FINDINGS: Several neuroimaging methods including diffusion imaging and positron emission tomography (PET) distinguish specific PD motor subtypes well, although findings are mixed. Furthermore, our review demonstrates that nTD-PD patients have more severe neuroalterations compared to TD-PD patients. More specifically, nTD-PD patients have deficits within striato-thalamo-cortical (STC) circuitry and other thalamocortical projections related to cognitive and sensorimotor function, while TD-PD patients tend to have greater cerebello-thalamo-cortical (CTC) circuitry dysfunction. CONCLUSIONS: Based on the literature, STC and CTC circuitry deficits seem to be the key features of PD and the subtypes. Future research should make greater use of multimodal neuroimaging and techniques that have higher sensitivity in delineating subcortical structures involved in motor diseases.

Differentiating Parkinson's disease motor subtypes: A radiomics analysis based on deep gray nuclear lesion and white matter.

OBJECTIVE: To investigate the feasibility of radiomics analysis of brain MR images to differentiate Parkinson's disease motor subtypes. METHODS: 42 postural instability gait difficulty (PIGD) patients, 92 tremor-dominant (TD) patients and 96 healthy controls were included from the Parkinson's Progressive Marker Initiative public database. For each subject, 4850 radiomic features from 148 cortical and 14 subcortical brain regions were extracted. The variance threshold and the least absolute shrinkage and selection operator were used to select the optimal features. Classification models based on Support Vector Machine, Logistic Regrcession, and Multi-Layer Perceptron were constructed to assess the performance of optimal features in the discrimination of the two subtypes. Correlations between radiomic features and clinical scores of the two subtypes were estimated. RESULTS: The Support Vector Machine demonstrated the best performance in discriminating between the two subtypes, and the mean area under the curve was 0.833 (specificity = 83.3%, sensitivity = 75.0%, and accuracy = 80.7%). For the postural instability gait difficulty patients, these optimal features in the hippocampal showed closed correlations with the Montreal Cognitive Assessment scores (P < 0.05). CONCLUSION: The results of our study provide preliminary evidence that radiomics analysis of brain MR images could allow discrimination between patients with TD, PIGD and control subjects and has great potential value in the clinical practice.

Stability of MDS-UPDRS Motor Subtypes Over Three Years in Early Parkinson's Disease.

Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated. Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability. Methods: Participants (n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years. Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes (p < 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [p < 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98-0.99] and higher TD/PIGD ratios (p < 0.05, OR 1.77, 95% CI: 1.29-2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669-0.876), sensitivity = 57.8%, and specificity = 89.7%. Conclusion: Only 50-62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.

Comparison of clinical features among Parkinson's disease subtypes: A large retrospective study in a single center.

INTRODUCTION: Tremor dominant (TD), postural instability/gait difficulty (PIGD), and akinetic-rigid (AR) subtypes are widely used in classifying patients with Parkinson's disease (PD). METHODS: We compared clinical characteristics between PD subtypes in a large retrospective cohort. Between 1998 and 2016, we included a total of 1003 patients with PD in this retrospective study. Six hundred ninety-four patients had more than one visit. Data were collected regarding motor/non-motor symptoms at the initial/final visits. Based on the prominent symptom at the initial visit, we classified patients into one of the four subtypes: TD, AR, gait difficulty, and mixed. Rapid progression was defined by emergence of falls, dementia, or dependency within 5years after onset. RESULTS: TD was the most prevalent subtype (44%), followed by AR (29%), mixed (18%), and gait difficulty (9%). Rapid progression was observed more frequently in gait difficulty compared to AR (OR: 3.59 P<0.001). Hallucinations at the final visit were more likely to occur in AR (OR: 2.36, P=0.005) and mixed (OR: 3.28, P<0.001) compared to TD. CONCLUSIONS: Our findings provide support for a distinction of four different PD subtypes: TD, AR, gait difficulty, and mixed. The gait difficulty subtype was distinguishable from the AR subtype.

Serum uric acid level and its association with motor subtypes and non-motor symptoms in early Parkinson's disease: PALS study.

OBJECTIVE: Uric acid has been found to be potentially neuroprotective in Parkinson's disease (PD). We investigated the relationship between serum uric acid levels and both motor and non-motor features in a prospective early PD cohort study. METHODS: Fasting serum uric acid levels were measured from 125 early PD patients. Demographic, clinical characteristics, motor and non-motor assessments were performed. Patients were categorized into three motor subtypes: tremor-dominant (TD), postural instability/gait difficulty (PIGD), and mixed. Non-motor symptoms were classified as present or absent based on the appropriate cut-offs for each non-motor instrument. RESULTS: Most patients had TD (n = 51, 40.8%) and mixed (n = 63, 50.4%) motor subtypes, while a minority had PIGD (n = 11, 8.8%) motor subtype. The mean serum uric acid levels were significantly different between the three motor subtypes (p = 0.0106), with the mixed subtype having the lowest serum uric acid levels. Using the TD subtype as reference, patients with higher serum uric acid levels were less likely to have the mixed (OR = 0.684; p = 0.0312) subtype as opposed to the TD subtype. Uric acid levels were not significantly different between the TD and PIGD subtypes. For non-motor symptoms, higher serum uric acid levels were significantly associated with less fatigue (OR = 0.693; p = 0.0408). CONCLUSION: Higher serum uric acid levels were associated with TD motor subtype and less fatigue in early PD, which could be related to its anti-oxidative properties. Uric acid could be an important biomarker for specific motor features and symptoms of fatigue in PD.