Clinical Symptoms Of Parkinson's Disease Research Articles

Estimating the sequence of biomarker changes in Parkinson's disease

ObjectiveTo estimate the sequence of several common biomarker changes in Parkinson's disease (PD) using a novel data-driven method. MethodsWe included 374 PD patients and 169 healthy controls (HC) from the Parkinson's Progression Markers Initiative (PPMI). Biomarkers, including the left putamen striatal binding ratio (SBR), right putamen SBR, left caudate SBR, right caudate SBR, cerebrospinal fluid (CSF) α-synuclein, and serum neurofilament light chain (NfL), were selected in our study. The discriminative event-based model (DEBM) was utilized to model the sequence of biomarker changes and establish the disease progression timeline. The estimated disease stages for each subject were obtained through cross-validation. The associations between the estimated disease stages and the clinical symptoms of PD were explored using Spearman's correlation. ResultsThe left putamen is the earliest biomarker to become abnormal among the selected biomarkers, followed by the right putamen, CSF α-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages are significantly different between PD and HC and yield a high accuracy for distinguishing PD from HC, with an area under the curve (AUC) of 0.98 (95% confidence interval 0.97–0.99), a sensitivity of 0.95, and a specificity of 0.92. Moreover, the estimated disease stages correlate with motor experiences of daily living, motor symptoms, autonomic dysfunction, and anxiety in PD patients. ConclusionWe determined the sequence of several common biomarker changes in PD using DEBM, providing data-driven evidence of the disease progression of PD.

The Endotoxin Hypothesis of Parkinson's Disease.

The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram-negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α-synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut-brain axis leads to neuroinflammation and spreading of α-synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α-synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The interplay between small vessel disease and Parkinson disease pathology: A longitudinal study

BackgroundCerebral small vessel disease (SVD) related brain changes have been found associated with various clinical symptoms of Parkinson disease (PD). On the other hand, PD pathology and treatment may also accelerate SVD progression. ObjectiveThe aim of this study is to explore the interplay between SVD and PD pathology using longitudinal dataset. MethodsWe screened 66 healthy controls (HCs) and 114 patients from the Parkinson Progression Markers Initiative (PPMI) database. The peak width of skeletonized mean diffusivity (PSMD) was quantified from diffusion tensor images to reflect vascular pathologies at baseline and 24 months follow-up, and dopamine transporter (DAT) imaging data was used to represent the extent of dopaminergic neuronal degeneration at the same point time. We compared the PSMD between PD patients and HCs, and analyzed whether PSMD and DAT availability could predict each other’s progression using multiple regression analyses in PD patients. ResultsPSMD at baseline had no significant difference between the HCs and patients with PD (P = 0.169). Higher baseline PSMD was associated with less DAT reduction in the caudate (β = 0.216, P = 0.029), but not the putamen (β = 0.058, P = 0.552) in PD patients. Baseline caudate and putamen DAT availability had no significant association with PSMD progression (β = -0.006, P = 0.950; β = 0.017, P = 0.860, respectively). ConclusionsMild SVD might slow down PD pathology progression, while the effect of PD pathology on the progression of SVD was not significant.

Gene-related Parkinson's disease diagnosis via feature-based multi-branch octave convolution network

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly population. PD is irreversible and its diagnosis mainly relies on clinical symptoms. Hence, its effective diagnosis is vital. PD has the related gene mutation called gene-related PD, which can be diagnosed not only in the specific PD patients, but also in the healthiest people without clinical symptoms of PD. Since mutations in PD-related genes can affect healthy people, and unaffected PD-related gene carriers can develop into PD patients, it is very necessary to distinguish gene-related PD diseases. The magnetic resonance imaging (MRI) has a lot of information about brain tissue, which can distinguish gene-related PD diseases. However, the limited amount of the gene-related cohort in PD is a challenge for further diagnosis. Therefore, we develop a joint learning framework called feature-based multi-branch octave convolution network (FMOCNN), which uses MRI data for gene-related cohort PD diagnosis. FMOCNN performs sample-feature selection to learn discriminative samples and features and contains a deep neural network to obtain high-level feature representation from various feature types. Specifically, we first train a cardinality constrained sample-feature selection (CCSFS) model to select informative samples and features. We then establish a multi-branch octave convolution neural network (MBOCNN) to jointly train multiple feature inputs. High/low-frequency learning in MBOCNN is exploited to reduce redundant feature information and enhance the feature expression ability. Our method is validated on the publicly available Parkinson's Progression Markers Initiative (PPMI) dataset. Experiments demonstrate that our method achieves promising classification performance and outperforms similar algorithms.

A Multi-sequence MRI Study in Parkinson's Disease: Association Between Rigidity and Myelin.

The pathophysiology of rigidity in Parkinson's disease (PD) is poorly understood. Multi-sequence functional and structural brain MRI may further clarify the origin of this clinical characteristic. To examine both joint and unique relationships of MRI-based functional and structural imaging modalities to rigidity and other clinical features of PD. Retrospective cross-sectional study. 31 PD subjects (aged 68.0 ± 5.9 years, 21 males) with average disease duration 9.3 ± 5.4 years. Multi-echo GRASE, diffusion-weighted echo planar imaging (EPI), and blood oxygen level dependent contrast EPI T2*-weighted sequences on a 3T scanner. Myelin water fraction (MWF) and fractional anisotropy (FA) of 20 white-matter regions of interest (ROIs), and functional connectivity derived from resting-state fMRI among 56 ROIs were assessed. The Unified Parkinson's Disease Rating Scale-Part III, Montreal Cognitive Assessment, Beck Depression Index, and Apathy Rating Scales were used to assess motor and non-motor symptoms. Multiset canonical correlation analysis (MCCA) and canonical correlation analysis (CCA) were utilized to examine the joint and unique relationships of multiple imaging measures with clinical symptoms of PD. A permutation test was used to determine statistical significance (P < 0.05). MCCA revealed a single significant component jointly linking MWF, FA, and functional connectivity to age, bradykinesia, and leg agility, non-motor symptoms of cognition, depression, and apathy, but not rigidity (P=0.77), tremor (P=0.50 and 0.67 on the left and right side), or sex (P=0.54). After controlling for this joint component, CCA found a unique significant association between MWF and rigidity, but no other associations were detected, including with FA (P=0.87). MWF, FA, and functional connectivity can serve as multi-sequence imaging markers to characterize many PD symptoms. However, rigidity in PD is additionally associated with widespread myelin changes. 4 TECHNICAL EFFICACY: Stage 3.

Time-Specific Pattern of Iron Deposition in Different Regions in Parkinson's Disease Measured by Quantitative Susceptibility Mapping.

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

Identification of BAG2 and Cathepsin D as Plasma Biomarkers for Parkinson's Disease.

The current diagnosis of Parkinson’s disease (PD) mostly relies on clinical rating scales related to motor dysfunction. Given that clinical symptoms of PD appear after significant neuronal cell death in the brain, it is required to identify accessible, objective, and quantifiable biomarkers for early diagnosis of PD. In this study, a total of 20 patients with idiopathic PD and 20 age‐matched patients with essential tremor according to the UK Brain Bank Criteria were consecutively enrolled to identify peripheral blood biomarkers for PD. Clinical data were obtained by clinical survey and assessment. Using albumin‐depleted and immunoglobulin G‐depleted plasma samples, we performed immunoblot analysis of seven autophagy‐related proteins and compared the levels of proteins to those of the control group. We also analyzed the correlation between the levels of candidate proteins and clinical characteristics. Finally, we validated our biomarker models using receiver operating characteristic curve analysis. We found that the levels of BCL2‐associated athanogene 2 (BAG2) and cathepsin D were significantly decreased in plasma of patients with PD (P = 0.009 and P = 0.0077, respectively). The level of BAG2 in patients with PD was significantly correlated with Cross‐Culture Smell Identification Test score, which indicates olfactory dysfunction. We found that our biomarker model distinguishes PD with 87.5% diagnostic accuracy (area under the curve (AUC) = 0.875, P < 0.0001). Our result suggests BAG2 and cathepsin D as candidates for early‐diagnosis plasma biomarkers for PD. We provide the possibility of plasma biomarkers related to the autophagy pathway, by which decreased levels of BAG2 and cathepsin D might lead to dysfunction of autophagy.

Motor recovery and antidepressant effects of repetitive transcranial magnetic stimulation on Parkinson disease: A PRISMA-compliant meta-analysis.

Clinical symptoms of Parkinson disease (PD) included both motor and nonmotor symptoms. Previous studies indicated inconsistent results for the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor and depression in PD. The study aimed to assess the therapeutic effect of rTMS with different mode on motor and depression in PD using a meta-analysis. Articles published before July 2019 were searched based on the following databases (PubMed, Web of Science, Medline, Embase, and Google Scholar). The therapeutic effects were assessed by computing the standard mean difference (SMD) and a 95% confidence interval (CI). The present study indicated that rTMS showed significant therapeutic effects on motor in PD (SMD 2.05, 95% CI 1.57-2.53, I = 93.0%, P < .001). Both high-frequency (HF)-rTMS and low-frequency rTMS showed therapeutic effects on motor; stimulation over primary motor cortex (M1), supplementary motor area, dorsal lateral prefrontal cortex (DLPFC) or M1+DLPFC showed therapeutic effects; stimulation during "on" and "off" states showed therapeutic effects; the study showed long-term effect of rTMS on motor in PD. In addition, the study indicated that rTMS showed significant therapeutic effects on depression in PD (SMD 0.80, 95% CI 0.31-1.29, I = 89.1%, P < .001). Stimulation over left DLPFC showed significant therapeutic effects on depression in PD; only HF-rTMS showed therapeutic effects; ages, disease durations, numbers of pulses, and session durations displayed influence on the therapeutic effects of rTMS on depression in PD; the therapeutic effects on depression was long term. However, no significant difference in therapeutic effects on depression were showed between rTMS and oral Fluoxetine (SMD 0.74, 95% CI -0.83 to 2.31, I = 92.5%, P < .001). The rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.

ЭФФЕКТИВНОСТЬ АГОНИСТА ДОФАМИНОВЫХ НА КОГНИТИВНЫЕ ФУНКЦИИ У ПАЦИЕНТОВ СБОЛЕЗНЬЮ ПАРКИНСОНА

Parkinson's disease (PD) affects about 1-2% of the population over 65 years old and up to3-5% of people aged 85 years and older. PD is a neurode generative disease characterized by a combination of motor and non-motor symptoms. According to published data, non-motor symptoms (NMS) are detected in 70-100% of patients with PD. The main clinical symptoms of PD are well known, but it is necessary to continue to study changes in symptoms as they progress.

PARK2 and PARK7 Gene Polymorphisms as Risk Factors Associated with Serum Element Concentrations and Clinical Symptoms of Parkinson's Disease.

Besides clinical and imaging techniques, there is a lack of molecular makers for the diagnosis of Parkinson's disease (PD). There is an immense need to develop biomarkers associated with the phenotypes which may be valuable for individualized treatment. Single-nucleotide polymorphisms (PARK2: Ser167Asn (G>A) and Val380Leu (G>C); PARK7: IVS4 + 46G>A and IVS4 + 30T>G) in PD-related genes were examined to elucidate its relationship with concentration of serum elements and clinical symptoms of PD. A total of 214 PD patients and 213 controls from Indian population were genotyped using PCR and DNA sequencing methods. The serum element concentrations were detected and clinical symptoms were determined based on UPDRS scale and recorded at the time of sample collection. The IVS4 + 30T>G, Ser167Asn (G>A) and Val380Leu (G>C) polymorphisms appeared to alter element concentrations in PD. The patients with Ser167Asn polymorphism showed significant association with copper, iron and zinc that reinforces the role of A allele as a factor for change in the concentrations of elements, than those patients with G allele. In particular, patients with A allele of Ser167Asn have risk of having high serum iron concentration (OR 11.55, 95% CI 5.59-23.85), which are associated with dementia and postural imbalance. Similar results were observed for Val380Leu (G>C) and IVS4 + 30T>G polymorphisms which suggest their role in element concentration and neurological symptoms. Overall, our study demonstrates the influence of polymorphisms of PD genes on element concentrations and clinical symptoms. Results of this study may be taken into account when considering the contributing factors for PD symptoms.

Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance

Parkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.

Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons.

Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (αSyn-WT), a protein associated with PD, and its mutant variants αSyn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of αSyn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of αSyn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with αSyn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all αSyn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by αSyn-WT and -A53T but not by αSyn-A30P. Correspondingly, colocalization of αSyn and the autophagy marker LC3 was reduced for αSyn-A30P compared with the other αSyn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both αSyn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that αSyn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered.

Morphological alterations in the caudate, putamen, pallidum, and thalamus in Parkinson's disease.

Like many neurodegenerative diseases, the clinical symptoms of Parkinsons disease (PD) do not manifest until significant progression of the disease has already taken place, motivating the need for sensitive biomarkers of the disease. While structural imaging is a potentially attractive method due to its widespread availability and non-invasive nature, global morphometric measures (e.g., volume) have proven insensitive to subtle disease change. Here we use individual surface displacements from deformations of an average surface model to capture disease related changes in shape of the subcortical structures in PD. Data were obtained from both the University of British Columbia (UBC) [n = 54 healthy controls (HC) and n = 55 Parkinsons disease (PD) patients] and the publicly available Parkinsons Progression Markers Initiative (PPMI) [n = 137 (HC) and n = 189 (PD)] database. A high dimensional non-rigid registration algorithm was used to register target segmentation labels (caudate, putamen, pallidum, and thalamus) to a set of segmentation labels defined on the average-template. The vertex-wise surface displacements were significantly different between PD and HC in thalamic and caudate structures. However, overall displacements did not correlate with disease severity, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The results from this study suggest disease-relevant shape abnormalities can be robustly detected in subcortical structures in PD. Future studies will be required to determine if shape changes in subcortical structures are seen in the prodromal phases of the disease.

Early Parkinson's disease symptoms in -synuclein transgenic monkeys

Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by genetic mutations in α-synuclein (α-syn) or duplication of wild-type α-syn; PD is characterized by the deposition of α-syn aggregates, indicating a gain of toxicity from accumulation of α-syn. Although the major neuropathologic feature of PD is the degeneration of dopaminergic (DA) neurons in the substantia nigra, non-motor symptoms including anxiety, cognitive defect and sleep disorder precede the onset of motor impairment, and many clinical symptoms of PD are not caused by degeneration of DA neurons. Non-human primate models of PD are important for revealing the early pathology in PD and identifying effective treatments. We established transgenic PD rhesus monkeys that express mutant α-syn (A53T). Six transgenic A53T monkeys were produced via lentiviral vector expressing A53T in fertilized monkey eggs and subsequent embryo transfer to surrogates. Transgenic A53T is expressed in the monkey brain and causes age-dependent non-motor symptoms, including cognitive defects and anxiety phenotype, without detectable sleeping disorders. The transgenic α-syn monkeys demonstrate the specific early symptoms caused by mutant α-syn and provide insight into treatment of early PD.

MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)로 유도된 Parkinson's Disease 동물 모델을 이용한 향사양위탕의 신경 세포 보호 효과

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

Actigraphy monitoring of symptoms in patients with Parkinson's disease

Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the “gold-standard” tool in assessing the severity of symptoms in patients with Parkinson's disease (PD), not all activity-related disease symptoms can be accurately captured by the well-established clinical rating scale. Using an alternative approach, this study examined the level of physical activity measured by actigraphy over time and whether change in physical activity was associated with disease severity assessed by UPDRS.We used a longitudinal design in which physical activity and disease severity were assessed repeatedly during a 4-month interval, over a 3-year observational period, in a sample of 61 patients with idiopathic PD and a control group of 32 neurologically intact individuals. Physical activity data during awake-time were analyzed using the power-law exponent (PLE) method. Correlational relationships between changes in maxima values of PLE and scores of total UPDRS, UPDRS—part II (Activities of Daily Living), and UPDRS—part III (Motor Examination) in patients with PD were examined. Results show an increase in maxima values of PLE and the UPDRS total score in PD patients and that there is a positive association between changes in maxima values and total UPDRS score (r=0.746, p=0.032), UPDRS—part II score (r=0.687, p=0.027), and UPDRS—part III score (r=0.893, p=0.018). There was no significant change in the level of physical activity over time for the controls.Findings from this study indicate that change in physical activity, as captured by actigraphy, is associated with increased severity in patients' clinical symptoms of PD over time. Thus, these data suggest that, when used in conjunction with the conventional UPDRS measure, an actigraphic measure of physical activity may provide clinicians an adjunct measurement approach to monitor patients' activity-based disease progression or responses to treatment in outpatient clinic settings.

Cost-effectiveness aralysis of pramipexole combined with levodopa/benserazide in the hospitalized Parkinson's disease patients

Objective To assess cost-effectiveness of pramipexole and levodopa/benseraside in the hospitalized Parkinson's disease (PD) patient.Methods 81 PD patients were divided into group A(levodopa/benserazide group) and group B( pramipexole combined with levodopa/benserazide group) according to different pharmacotherapy.The curative effects and costs of hospitalized PD patients were evaluated.The curative effects were evaluated by unified Parkinson's disease rating scale (UPDRS).Results There were 44 patients in group A and 37 patients in group B.Although B group in drug costs and treatment costs were increased more significantly than A group ( P ＜0.01),but declined markedly UPDRS after treatment ( P ＜ 0.05 ) than A group.Pramipexole can be applied in all kinds of Hoehn and Yahr states in PD.Conclusion Although the combination of pramipexole would increase drug costs and treatment costs,but could improve the clinical symptoms of PD,and can be applied to different stages of PD.It should be individualized recommendation in the Parkinson's patients. Key words: Parkinson's disease; levodopa/benserazide; Pramipexole

Effects of Chinese herbal medicine Bushen Huoxue Granule on quality of life of patients with Parkinson disease: a randomized, double-blinded and placebo-controlled trial

The main clinical symptoms of Parkinson disease (PD) are resting tremor, muscle rigidity and bradykinesia. There is currently no effective treatment for PD, and dyskinesia symptoms affect the quality of life of patients with PD. The Chinese medicine therapy used for reinforcing kidney and activating blood circulation in treatment of PD was reported to achieve good clinical effects. To study the effects of Bushen Huoxue Granule, a compound traditional Chinese herbal medicine, on the quality of life of patients with PD. A total of 120 patients were enrolled from General Hospital of the People's Liberation Army in China and divided into two groups randomly. Patients in the control group were treated with a placebo and in the treatment group with Bushen Huoxue Granule based on treating with levodopa. A double-blinded clinical trial was adopted over a 3-month treatment with a follow-up period lasting 6 months. Unified Parkinson Disease Rating Scale II (UPDRS II), questionnaire-39 (PDQ-39) and Parkinson's disease sleep scale (PDSS) were adopted to measure the quality of life at baseline, after 3 months of treatment and at a 6-month follow-up. Bushen Huoxue Granule showed a higher efficacy than the control in improving life quality of patients with PD by improving scores of UPDRS II, PDQ-39 and PDSS (P<0.05). No adverse effects were found in this trial. Bushen Huoxue Granule can markedly improve the quality of life of patients with PD.

Glia: Initiators and progressors of pathology in Parkinson's disease

Glia are traditionally known as support cells for neurons, and their role in neurodegeneration has been largely considered secondary to neuronal dysfunction. We review newer concepts on glial function and assess glial changes in Parkinson's disease (PD) at the time of disease initiation when α-synuclein is accumulating in brain tissue but there is limited neuronal loss, and also as the disease progresses and neuronal loss is evident. Of the two main types of astrocytes, only protoplasmic astrocytes are involved in PD, where they become nonreactive and accumulate α-synuclein. Experimental evidence has shown that astrocytic α-synuclein deposition initiates the noncell autonomous killing of neurons through microglial signaling. As the disease progresses, more protoplasmic astrocytes are affected by the disease with an increasing microglial response. Although there is still controversy on the role microglia play in neurodegeneration, there is evidence that microglia are activated early in PD and possibly assist with the clearance of extracellular α-synuclein at this time. Microglia transform to phagocytes and target neurons as the disease progresses but appear to become dysfunctional with increasing amounts of ingested debris. Only nonmyelinating oligodendroglial cells are affected in PD, and only late in the disease process. Glial cells are responsible for the progression of PD and play an important role in initiating the early tissue response. In particular, early dysfunction and α-synuclein accumulation in astrocytes causes recruitment of phagocytic microglia that attack selected neurons in restricted brain regions causing the clinical symptoms of PD.

How useful are stem cells in PD therapy?

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The onset of PD is usually after the age of 50. Clinical symptoms of PD are not manifested until 60-80% of dopaminergic neurons in the midbrain have been affected. Cell replacement has been a promising approach for the treatment of PD. Fetal mesencephalic dopaminergic neurons seemed to improve the motor disability in patients in some early studies. However, the clinical application of this approach may be limited by ethical and logistic concerns, as well as by side effects. On the other hand, embryonic stem (ES) cells are promising candidates because of their ability to provide an unlimited supply of specific cell types, their accessibility to genetic modifications, and their broad developmental potentials. Transplants of undifferentiated ES cells were able to proliferate and fully differentiate into dopaminergic neurons in a rodent PD model. One of the concerns though is the risk of tumor formation. The tumorigenic potential of ES cells seems to be greatly reduced when cells are predifferentiated into dopaminergic neurons in vitro before implantation. Recent developments in the induction of pluripotent stem cells from somatic adult cells provide a tremendous opportunity for this field. Initial success has been reported in a rodent PD model using iPS cells (induced pluripotent stem cells). However, whether this initial result can be successfully translated into human clinical studies still needs to be determined.