Systemic Review on Parkinson’s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson’s Symptoms

Parkinson’s Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016–2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg (p = 0.0138) and 100 mg (p = 0.0006) have improved the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression—Change (CGI-C), Clinical Global Impression—Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson’s Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.

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Comparative Analysis of Acute Levodopa Challenge Test and the Outcomes of Deep Brain Stimulation in Parkinson's Disease

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0041-1739226 ◽

2021 ◽

Author(s):

Yusheng Chen ◽

Jie Zu ◽

Wei Zhang ◽

Chuanying Xu ◽

Guiyun Cui ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Linear Correlation ◽

Rating Scale ◽

Challenge Test ◽

Muscle Rigidity ◽

Motor Symptoms ◽

Deep Brain

Abstract Background We study the correlation between the preoperative levodopa challenge test and the efficacy of deep brain stimulation (DBS) surgery in Parkinson's disease (PD). Methods Fifty patients with PD who underwent DBS treatment in our hospital from October 2016 to October 2017 were enrolled in this study. Using the Unified Parkinson Disease Rating Scale-III (UPDRS-III) as an indicator, we analyzed the improvement in motor symptoms on the levodopa challenge test and by DBS surgery. We also discussed the correlation between the effects of the levodopa challenge test and DBS surgery. Results There was no correlation between the results of the levodopa challenge test and DBS surgery. There was a linear correlation between muscle rigidity and bradykinesia, whereas the linear correlation between other symptoms was weak. Conclusion The levodopa challenge test can be used as a screening tool for patients undergoing DBS surgery, and can predict the degree of improvement in muscle rigidity and bradykinesia surgery. However, the prediction of the degree of improvement of total motor symptoms is poor.

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Boxing vs Sensory Exercise for Parkinson’s Disease: A Double-Blinded Randomized Controlled Trial

Neurorehabilitation and Neural Repair ◽

10.1177/15459683211023197 ◽

2021 ◽

pp. 154596832110231

Author(s):

Kishoree Sangarapillai ◽

Benjamin M. Norman ◽

Quincy J. Almeida

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Controlled Trial ◽

Repeated Measures ◽

Rating Scale ◽

Controlled Trial ◽

Motor Symptoms ◽

Post Intervention ◽

Randomized Controlled ◽

Double Blinded

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

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Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

Microbial Cell Factories ◽

10.1186/s12934-021-01589-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-yi Kuai ◽

Xiao-han Yao ◽

Li-juan Xu ◽

Yu-qing Zhou ◽

Li-ping Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Gastrointestinal Dysfunction ◽

Before And After ◽

Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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Dance Rhythms Improve Motor Symptoms in Individuals with Parkinson’s Disease: A Randomized Clinical Trial

Journal of Dance Medicine & Science ◽

10.12678/1089-313x.031522a ◽

2021 ◽

Author(s):

Jéssica A. Moratelli ◽

Kettlyn H. Alexandre ◽

Leonessa Boing ◽

Alessandra Swarowsky ◽

Clynton L. Corrêa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Randomized Clinical Trial ◽

Rating Scale ◽

Freezing Of Gait ◽

Motor Symptoms ◽

Score Change ◽

Significant Difference ◽

Binary Group

Background: Evidence-based practices involving dance modalities found in binary (two-beat rhythm) or quaternary (four-beat rhythm) show that dance positively influences the motor aspects of disease.Aim: This randomized clinical trial aimed to analyze the effect of two dance rhythm (binary and quaternary) on the balance, gait, and mobility in individuals with Parkinson’s disease (PD). Methods: Thirty-one individuals with PD were randomized into the binary group (n = 18) and the quaternary group (n = 13). Both groups participated in different dance rhythms lasting 12 weeks, twice a week, for 45 minutes. Results: The binary group showed a significant difference in balance (p = 0.003), freezing of gait (p = 0.007), as well as in the motor aspects of MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), with emphasis on the total values with a score change of 3.23. In the quaternary group, significant differences were found in balance (p = 0.021) with a score change of -2.54 and in the motor aspects of the MDS-UPDRS Part III where the total values stood out with a change of 3.54. Discussion: When comparing the possible effects of binary and quaternary rhythms on the motor symptoms of individuals with PD, it was demonstrated that binary rhythm improved balance, freezing gait, and UPDRSIII. As for the quaternary rhythm, the benefits were in balance and the UPDRSIII. Conclusion: The binary and the quaternary rhythm dance protocols positively influenced the motor symptoms of individuals with PD after 12 weeks of intervention.

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Potential Role of Caffeine in the Treatment of Parkinson’s Disease

The Open Neurology Journal ◽

10.2174/1874205x01610010042 ◽

2016 ◽

Vol 10 (1) ◽

pp. 42-58 ◽

Cited By ~ 8

Author(s):

Mohsin H.K. Roshan ◽

Amos Tambo ◽

Nikolai P. Pace

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Clinical Trials ◽

Neurodegenerative Disorder ◽

Lewy Bodies ◽

Substantia Nigra Pars Compacta ◽

Muscle Rigidity ◽

Therapeutic Effects ◽

Motor Symptoms ◽

Wide Range

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from bothin vivoandin vitrostudies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2Areceptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

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The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.650053 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chin-Song Lu ◽

Hsiu-Chen Chang ◽

Yi-Hsin Weng ◽

Chiung-Chu Chen ◽

Yi-Shan Kuo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactobacillus Plantarum ◽

Outcome Measures ◽

Rating Scale ◽

Controlled Trial ◽

Secondary Outcome ◽

Motor Deficits ◽

Motor Symptoms ◽

Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

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Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

Neurodegenerative Diseases ◽

10.1159/000489311 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 127-132 ◽

Cited By ~ 3

Author(s):

Jeong-Yoon Lee ◽

Ji Sun Kim ◽

Wooyoung Jang ◽

Jinse Park ◽

Eungseok Oh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Parkinson Disease ◽

Cognitive Dysfunction ◽

Rating Scale ◽

White Matter Lesions ◽

Motor Dysfunction ◽

Motor Symptoms ◽

Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

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Genetic Impact on Clinical Features in Parkinson’s Disease: A Study on SNCA-rs11931074

Parkinson s Disease ◽

10.1155/2018/2754541 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Li Shu ◽

Dongxiao Liang ◽

Hongxu Pan ◽

Qian Xu ◽

Jifeng Guo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Features ◽

Rating Scale ◽

Motor Symptoms ◽

Nonmotor Symptoms ◽

Association Analyses ◽

Comorbidity Burden ◽

Severe Motor ◽

Genetic Impact

SNCA-rs11931074 had been demonstrated to be strongly correlated with PD risk. However, there was lack of comprehensive analysis of SNCA-rs11931074-related clinical features which may help explain clinical heterogeneity of PD. In our study, we performed association analyses on the relationship between SNCA-rs11931074 and motor symptoms, nonmotor symptoms, and comorbidities in PD. 611 rs11931074 carriers and 113 rs11931074 noncarriers were enrolled. In the clinical phenotype analyses, the Unified Parkinson’s Disease Rating Scale part II (UPDRS II) and part III (UPDRS III) scores of rs11931074 carriers were lower than those of noncarriers (SC: −0.083, p=0.035; SC: −0.140, p≤0.001). The Charlson Comorbidity Index (CCI) score of carriers was lower than that of noncarriers (SC: −0.097, p=0.009). No significant statistical differences were found between the variant and other clinical features such as motor complications and nonmotor symptoms. The SNCA-rs11931074 carriers may present with more benign clinical profiles than noncarriers with less severe motor symptoms and comorbidity burden.

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Adaptive deep brain stimulation as advanced Parkinson’s disease treatment (ADAPT study): protocol for a pseudo-randomised clinical study

BMJ Open ◽

10.1136/bmjopen-2019-029652 ◽

2019 ◽

Vol 9 (6) ◽

pp. e029652 ◽

Cited By ~ 7

Author(s):

Dan Piña-Fuentes ◽

Martijn Beudel ◽

Simon Little ◽

Peter Brown ◽

D L Marinus Oterdoom ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Clinical Study ◽

Side Effects ◽

Brain Stimulation ◽

Rating Scale ◽

Motor Symptoms ◽

Internal Globus Pallidus ◽

Deep Brain

IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson’s disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson’s disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.

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A clinical rating scale of speech dysfunction on Parkinson's disease

South African Journal of Communication Disorders ◽

10.4102/sajcd.v25i1.371 ◽

1978 ◽

Vol 25 (1) ◽

Author(s):

Alison K. Thompson

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Muscle Rigidity ◽

Clinical Use ◽

Clinical Notes ◽

Clinical Rating ◽

Research Findings ◽

Clinical Rating Scale

The speech dysfunction of Parkinson's disease is complex and individually variable owing to the interaction of muscle rigidity, tremor and disturbance of movement. Eight speech dimensions which are characteristically disturbed in Parkinson's disease are discussed with reference to available research findings. In order to provide a more detailed description of the speech than could be obtained by clinical notes alone, a speech rating scale has been developed, and is presented in summarized form for clinical use. Incidence and progression of the speech dysfunction are considered in addition to the problems of assessment peculiar to the patient with Parkinson's disease.

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